Avelumab in Metastatic or Locally Advanced Solid Tumors (JAVELIN Solid Tumor)

October 26, 2021 updated by: EMD Serono Research & Development Institute, Inc.

A Phase I, Open-label, Multiple-ascending Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of Avelumab (MSB0010718C) in Subjects With Metastatic or Locally Advanced Solid Tumors and Expansion to Selected Indications

This is a Phase 1, open-label, dose-escalation trial of avelumab [antibody targeting programmed death ligand 1 (anti PD-L1)] with consecutive parallel group expansion in participants with selected tumor indications. New recruitment is open for all active cohorts.

Active cohorts: Escalation revised dosing regimen cohort.

Closed cohorts: Non-small cell lung cancer (NSCLC, first line), NSCLC (post-platinum), metastatic breast cancer (MBC), colorectal cancer (CRC), urothelial carcinoma (secondary), mesothelioma, gastric/GEJ cancer (first line switch maintenance and second line), and ovarian cancer (secondary and platinum refractory + liposomal doxorubicin), renal cell carcinoma (second line) melanoma and head, neck squamous cell carcinoma (HNSCC), castrate-resistant prostate cancer (CRPC), adrenocortical carcinoma (ACC) urothelial carcinoma (efficacy), gastric/gastroesophageal junction (GEJ) cancer (third line), renal cell carcinoma (RCC, first line) and escalation phase .

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

1756

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Wilrijk, Belgium, 2610
        • GZA Ziekenhuizen - Campus Sint-Augustinus
  • Czechia
      • Benesov, Czechia, 256 01
        • Nemocnice Rudolfa a Stefanie Benesov, a.s.
  • France
      • Angers cedex 2, France, 49055
        • ICO - Site Paul Papin - service d'oncologie medicale
      • Lyon, France, 69008
        • Centre LEON BERARD
      • Nice cedex 02, France, 06189
        • Centre Antoine Lacassagne
      • Strasbourg Cedex, France, 67000
        • Centre Paul Strauss - Service de Médecine Oncologique
  • Germany
      • Mainz, Germany, 55131
        • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz - I. Medizinische Klinik Gastroenterologie u Hepato.
      • Villingen-Schwenningen, Germany, 78052
        • Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH - Innere Medizin II Haematologie / Onkologie
  • Korea, Republic of
      • Seongnam-si, Korea, Republic of, 13620
        • Seoul National University Bundang Hospital
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center
      • Seoul, Korea, Republic of, 02841
        • Korea University Anam Hospital
      • Seoul, Korea, Republic of, 06591
        • The Catholic University of Korea, Seoul St. Mary's Hospital
      • Seoul, Korea, Republic of, 06273
        • Gangnam Severance Hospital, Yonsei University Health System
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center
      • Seoul, Korea, Republic of, 03722
        • Severance Hospital, Yonsei University
  • Poland
      • Warszawa, Poland, 02-781
        • Centrum Onkologii-Instytut im. M. Sklodowskiej Curie - Dept of Digestive System Oncology
  • Taiwan
      • Tainan, Taiwan, 704
        • National Cheng Kung University Hospital
      • Taipei, Taiwan, 100
        • National Taiwan University Hospital
  • United Kingdom
      • London, United Kingdom, W1G 6AD
        • Sarah Cannon Research Institute UK
      • Plymouth, United Kingdom, PL6 8BQ
        • Derriford Hospital - Dept of Oncology Clinical Trials
  • United States
    • Arizona
      • Goodyear, Arizona, United States, 85338
        • Cancer Treatment Centers of America - Western Regional Medical Center
      • Scottsdale, Arizona, United States, 85258
        • Pinnacle Oncology Hematology
      • Scottsdale, Arizona, United States, 85258-4550
        • Scottsdale Healthcare Corporation
    • Arkansas
      • Rogers, Arkansas, United States, 72758
        • Highlands Oncology Group
    • California
      • Anaheim, California, United States, 92801
        • Pacific Cancer Medical Center, Inc.
      • Encinitas, California, United States, 92024
        • California Cancer Associates for Research & Excellence, INC
      • Inglewood, California, United States, 90305
        • Healing Hands Oncology and Medical Care
      • La Jolla, California, United States, 92037
        • Scripps Health Dba Scripps Clinical Research Services
      • Los Angeles, California, United States, 90025
        • The Angeles Clinic and Research Institute - West LA
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center - Oncology
      • Sacramento, California, United States, 95817
        • University of California Davis Health System
      • San Diego, California, United States, 92123
        • Sharp Memorial Hospital
    • District of Columbia
      • Washington, District of Columbia, United States, 20057
        • Georgetown University Medical Center- Research Parent
    • Florida
      • Fort Lauderdale, Florida, United States, 33308
        • Holy Cross Hospital
      • Miami, Florida, United States, 33136
        • University of Miami
      • Port Saint Lucie, Florida, United States, 34952
        • Hematology - Oncology Associates of Treasure Coast - Hematology-Oncology Associates of Treasure Coast
      • Sarasota, Florida, United States, 34232
        • Florida Cancer Specialists
    • Georgia
      • Athens, Georgia, United States, 30607
        • Northeast Georgia Cancer Care, LLC
      • Atlanta, Georgia, United States, 30318
        • Peachtree Hematology-Oncology Consultants, PC
      • Augusta, Georgia, United States, 30912
        • Augusta University - formerly Georgia Regents University
      • Marietta, Georgia, United States, 30060
        • Northwest Georgia Oncology Centers PC
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medical Center
    • Indiana
      • Lafayette, Indiana, United States, 47905
        • Horizon Oncology Research, Inc
    • Maryland
      • Baltimore, Maryland, United States, 21287-7049
        • The Johns Hopkins Hospital
      • Bethesda, Maryland, United States, 20892
        • National Cancer Institute
      • Bethesda, Maryland, United States, 20817
        • RCCA MD LLC - Bethesda
      • Rockville, Maryland, United States, 20850
        • Maryland Oncology Hematology, P.A.
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
      • Detroit, Michigan, United States, 48202
        • Henry Ford Medical Center
      • Lansing, Michigan, United States, 48910
        • Michigan State University
    • Minnesota
      • Minneapolis, Minnesota, United States, 55407
        • Virginia Piper Cancer Institute
    • Missouri
      • Kansas City, Missouri, United States, 64131
        • Kansas City Research Institute, LLC - Phase I Unit
      • Saint Louis, Missouri, United States, 63110
        • Washington University in St. Louis
    • New Mexico
      • Farmington, New Mexico, United States, 87401
        • San Juan Oncology Associates
    • New York
      • Bronx, New York, United States, 10461
        • Montefiore Medical Center PRIME
      • New York, New York, United States, 10032
        • Columbia University College of Phys & Surgeons
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • University of North Carolina at Chapel Hill
      • Huntersville, North Carolina, United States, 28078
        • Carolina BioOncology Institute, LLC - Cancer Therapy and Research Center
    • Ohio
      • Cincinnati, Ohio, United States, 45267-0502
        • UC Health Clinical Trials Office
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Case Medical Center - Case Comprehensive Cancer Center
      • Columbus, Ohio, United States, 43210-1228
        • OSU - James Comprehensive Cancer Center - Division of Hematology
      • Columbus, Ohio, United States, 43219
        • Mid Ohio Oncology Hematology, DBA The Mark H. Zangmeister Center - d/b/a The Mark H. Zangmeister Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma University Medical Center
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Penn State Univ. Milton S. Hershey Medical Center - MSHMC Cardiology
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29245
        • Medical University of South Carolina
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • The West Clinic
      • Memphis, Tennessee, United States, 38120
        • Baptist Cancer Center
      • Nashville, Tennessee, United States, 37203
        • SCRI - Tennessee Oncology
    • Texas
      • Dallas, Texas, United States, 75246
        • Texas Oncology, P.A
      • Houston, Texas, United States, 77030
        • Oncology Consultants, P.A.
      • Tyler, Texas, United States, 75702
        • Texas Oncology, P.A. - Tyler
    • Washington
      • Lakewood, Washington, United States, 98499-3071
        • Northwest Medical Specialties, PLLC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria for dose escalation and expansion phase:

  • Signed written informed consent
  • Male or female participants aged greater than or equal to 18 years
  • Participants must have histologically or cytologically proven metastatic or locally advanced solid tumors, for which no standard therapy exists or standard therapy has failed. Availability of tumor archival material or fresh biopsies is optional for participants in dose escalation
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at trial entry and an estimated life expectancy of at least 3 months
  • Disease must be measurable with at least 1 uni-dimensional measurable lesion by RECIST 1.1, except for participants with metastatic castrate-resistant prostate cancer (mCRPC) or metastatic breast cancer (MBC) who may be enrolled with objective evidence of disease without a measureable lesion
  • Adequate hematological, hepatic and renal function as defined in the protocol
  • Effective contraception for both male and female participants if the risk of conception exists
  • Other protocol defined inclusion criteria could apply

Inclusion Criteria for expansion phase:

  • Participants must have relapsed, refractory, or progressive disease following last line of treatment (with the exception of the gastric and gastroesophageal junction (GEJ) cancer cohort, which does not require progression). Availability of tumor archival material or fresh biopsies (excluding bone biopsies) is mandatory for eligibility in the expansion cohorts. For participants in the MBC cohort, the biopsy or surgical specimen must have been collected within 90 days prior to the first investigational medicinal product (IMP) administration. Specifically, the following will be required:
  • NSCLC post platinum doublet: Histologically or cytologically confirmed stage IIIB or stage IV NSCLC that has progressed after 1 line of platinum-containing doublet chemotherapy. Participants should have received only 1 line of platinum-containing treatment for metastatic disease (i.e., adjuvant treatment with a platinum-containing regimen is not sufficient for eligibility because not received in the context of a metastatic disease). Participants in the NSCLC cohort will only be enrolled in USA
  • NSCLC first line: Stage IV (per 7th International Association for the Study of Lung Cancer [IASLC] classification) or recurrent NSCLC that is histologically proven. Participants must not have received treatment for their metastatic or recurrent disease. No activating epidermal growth factor receptor (EGFR) mutation nor ALK translocation/re-arrangement
  • Gastric and GEJ cancer: Histologically confirmed, unresectable locally advanced or metastatic adenocarcinoma of the gastric and gastro-esophageal junction, treated with first-line chemotherapy combination with or without disease progression. Participants should have received no more than 1 line of treatment for metastatic disease. Participants should not have been treated with trastuzumab (but can be Human Epidermal growth factor Receptor 2 [HER2] positive). Participants who received any platinum containing doublet or triplet as a neoadjuvant chemotherapy strategy, but are not ultimately candidates for surgery will also be eligible, as long as they did not have progressive disease after completion of the neoadjuvant chemotherapy. In addition, participants with gastric cancer can enter in the study if their white blood cell (WBC) and lymphocyte count is as defined in the protocol
  • MBC: Participants must have histologically confirmed locally advanced or MBC and have tumor that is refractory to or progressive after standard of care therapy. Participants must have received no more than 3 prior lines of cytotoxic therapy for metastatic disease. Participants must have received a taxane and an anthracycline, unless contra-indicated
  • Secondary expansion cohorts: Metastatic colorectal cancer (mCRC), Metastatic castrate-resistant prostate cancer (mCRPC), melanoma, ovarian cancer, ACC, mesothelioma, urothelial carcinoma and renal cell carcinoma as defined in the protocol

  • Efficacy expansion cohorts: Gastric and GEJ cancer (third line), ovarian cancer (platinum Refractory + liposomal doxorubicin), urothelial carcinoma, and HNSCC as defined in the protocol

    • Other protocol defined inclusion criteria for expansion phase could apply

Exclusion Criteria for dose escalation and expansion phase:

  • Concurrent treatment with a non-permitted drug
  • Prior therapy with specific antibody/drug targeting T cell co-regulatory proteins (immune checkpoints)
  • Concurrent anticancer treatment, major surgery, or use of any investigational drug within 28 days before the start of trial treatment; or concurrent systemic therapy with immunosuppressive agents, use of hormonal agents within 7 days before the start of trial treatment as defined in the protocol. Note: Participants receiving bisphosphonate or denosumab are eligible provided treatment was initiated at least 14 days before the first dose of avelumab.
  • Previous malignant disease other than the target malignancy to be investigated in this trial within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ
  • Rapidly progressive disease (for example, tumor lysis syndrome)
  • Active or history of central nervous system metastases
  • Receipt of any organ transplantation including allogeneic stem-cell transplantation
  • Significant acute or chronic infections as defined in the protocol
  • Active or history of any autoimmune disease (Participants with diabetes Type 1, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible) or immunodeficiencies
  • Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma
  • Persisting toxicity related to prior therapy greater than Grade 1 NCI-CTCAE v4.0, however sensory neuropathy less than or equal to Grade 2 is acceptable
  • Pregnancy or lactation period
  • Known alcohol or drug abuse
  • Clinically significant (that is, active) cardiovascular disease
  • All other significant diseases (for example, inflammatory bowel disease), which, in the opinion of the investigator, might impair the Participant's tolerance of trial treatment
  • Any psychiatric condition that would prohibit the understanding or rendering of informed consent
  • Legal incapacity or limited legal capacity
  • Non-oncology vaccine therapies for prevention of infection disease (for example, seasonal flu vaccine, human papilloma virus vaccine) within 4 weeks of study drug administration. Vaccination while on study is also prohibited except for administration of the inactivated influenza vaccine

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation Cohort: Avelumab 1.0 mg/kg
Participants with metastatic or locally advanced solid tumors received intravenous infusion of Avelumab at a dose of 1.0 milligrams per kilogram (mg/kg) once every 2 weeks in dose escalation cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or investigational medicinal product (IMP) occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Dose Escalation Cohort: Avelumab 3.0 mg/kg
Participants with metastatic or locally advanced solid tumors received intravenous infusion of Avelumab at a dose of 3.0 mg/kg once every 2 weeks in dose escalation cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Dose Escalation Cohort: Avelumab 10.0 mg/kg
Participants with metastatic or locally advanced solid tumors received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in dose escalation cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Dose Escalation Cohort: Avelumab 20.0 mg/kg
Participants with metastatic or locally advanced solid tumors received intravenous infusion of Avelumab at a dose of 20.0 mg/kg once every 2 weeks in dose escalation cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Dose Escalation Cohort: Avelumab 10.0 mg/kg Weekly
Participants with metastatic or locally advanced solid tumors received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once weekly for the first 12 weeks and once every 2 weeks starting Week 13 in dose escalation cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Primary Expansion Cohort: NSCLC, Post-platinum Doublet
Participants with non-small cell lung cancer (NSCLC), who had progressed after 1 line of platinum-containing doublet chemotherapy received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in primary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Primary Expansion Cohort: NSCLC, First Line
Participants with non-small cell lung cancer (NSCLC), first line received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in primary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Primary Expansion Cohort: Metastatic Breast Cancer
Participants with metastatic breast cancer received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in primary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Primary Expansion Cohort: GC/GEJC Progressed
Participants with gastric (GC) and gastroesophageal junction cancer (GEJC) who progressed on or after first line chemotherapy received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in primary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Primary Expansion Cohort: GC/GEJC Non Progressed
Participants with gastric (GC) and gastroesophageal junction cancer (GEJC) who non-progressed on or after first-line chemotherapy received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in primary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Secondary Expansion Cohort: Colorectal Cancer
Participants with colorectal cancer received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in secondary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Secondary Expansion Cohort: Castrate-resistant Prostate Cancer
Participants with castrate-resistant prostate cancer received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in secondary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Secondary Expansion Cohort: Adrenocortical Carcinoma
Participants with adrenocortical carcinoma received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in secondary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Secondary Expansion Cohort: Melanoma
Participants with melanoma received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in secondary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Secondary Expansion Cohort: Mesothelioma
Participants with mesothelioma received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in secondary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Secondary Expansion Cohort: Urothelial Carcinoma
Participants with urothelial carcinoma received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in secondary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Secondary Expansion Cohort: Ovarian Cancer
Participants with ovarian carcinoma received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in secondary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Secondary Expansion Cohort: Renal Cell Carcinoma (First Line)
Participants with Renal cell carcinoma received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks as a first-line therapy in secondary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Secondary Expansion Cohort: Renal Cell Carcinoma (Second Line)
Participants with Renal cell carcinoma who failed 1 prior systemic first-line regimen received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks as a second line treatment in secondary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Efficacy Expansion Cohort: Ovarian Cancer
Participants with ovarian carcinoma received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in efficacy expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Efficacy Expansion Cohort: Urothelial Carcinoma
Participants with urothelial carcinoma received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in efficacy expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Efficacy Expansion Cohort: GC/ GEJC, Third Line
Participants with gastric (GC) and gastroesophageal junction cancer (GEJC) who have failed both a first-line chemotherapy regimen and subsequent ramucirumab therapy, received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks as a third-line treatment in efficacy expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1
Experimental: Efficacy Expansion Cohort: HNSCC
Participants with head and neck squamous cell carcinoma (HNSCC) received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in efficacy expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Drug: Avelumab
Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.
Other Names:
  • MSB0010718C
  • Anti PD-L1

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Number of Participants Experiencing Dose Limiting Toxicities (DLTs)
Time Frame: Dose Escalation: Baseline up to Week 3
DLT: defined using National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.0, as any one of following: any Grade (Gr) >=3toxicity that is possibly/probably/ definitely related to avelumab, except for any of following: Gr 3 infusion-related reaction resolving within 6 hours and controlled with medical management, Transient Gr 3 flu-like symptoms/fever, which is controlled with medical management, Transient Gr 3 fatigue, local reactions, headache, nausea, emesis that resolves to <= Gr 1, Gr3 diarrhea, Gr 3 skin toxicity, Gr 3 liver function test increase that resolves to <= Gr1 in < 7 days after medical management has been initiated, Single laboratory values out of normal range that were unlikely related to study treatment according to investigator, did not have any clinical correlate, and resolved to <= Gr1 within 7 days with adequate medical management and tumor flare phenomenon defined as local pain, irritation/rash localized at sites of known/suspected tumor.
Dose Escalation: Baseline up to Week 3
Efficacy Expansion Cohort (Ovarian Cancer): Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), as Adjudicated by Independent Endpoint Review Committee (IERC)
Time Frame: Ovarian Cancer Efficacy Expansion: Baseline up to Day 620
Confirmed BOR was determined according to RECIST 1.1 and as adjudicated by an Independent Endpoint Review Committee (IERC) and defined as best response of any of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from date of randomization until disease progression/recurrence (taking smallest measurement recorded since start of treatment as reference). CR: Disappearance of all evidence of target/non-target lesions. PR: At least 30%reduction from baseline in sum of longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD: at least a 20% increase in SLD, taking as reference smallest SLD recorded from baseline/appearance of 1or more new lesions and unequivocal progression of non-target lesions.
Ovarian Cancer Efficacy Expansion: Baseline up to Day 620
Efficacy Expansion Cohort(Urothelial Carcinoma): Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), as Adjudicated by Independent Endpoint Review Committee (IERC)
Time Frame: Urothelial Carcinoma Efficacy Expansion: Baseline up to Day 931
Confirmed BOR was determined according to RECIST 1.1 and as adjudicated by an Independent Endpoint Review Committee (IERC) and defined as best response of any of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from date of randomization until disease progression/recurrence (taking smallest measurement recorded since start of treatment as reference). CR: Disappearance of all evidence of target/non-target lesions. PR: At least 30% reduction from baseline in sum of longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD: at least a 20% increase in SLD, taking as reference smallest SLD recorded from baseline/appearance of 1 or more new lesions and unequivocal progression of non-target lesions.
Urothelial Carcinoma Efficacy Expansion: Baseline up to Day 931
Efficacy Expansion Cohort (GC/GEJC, Third Line): Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), as Adjudicated by Independent Endpoint Review Committee (IERC)
Time Frame: GC/GEJC, Third Line Efficacy Expansion: Baseline up to Day 871
Confirmed BOR was determined according to RECIST 1.1 and as adjudicated by an Independent Endpoint Review Committee (IERC) and defined as best response of any of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from date of randomization until disease progression/recurrence (taking smallest measurement recorded since start of treatment as reference). CR: Disappearance of all evidence of target/non-target lesions. PR: At least 30% reduction from baseline in sum of longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD: at least a 20% increase in SLD, taking as reference smallest SLD recorded from baseline/appearance of 1 or more new lesions and unequivocal progression of non-target lesions.
GC/GEJC, Third Line Efficacy Expansion: Baseline up to Day 871
Efficacy Expansion Cohort (HNSCC): Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), as Adjudicated by Independent Endpoint Review Committee (IERC)
Time Frame: HNSCC Efficacy Expansion: Baseline up to Day 1072
Confirmed BOR was determined according to RECIST 1.1 and as adjudicated by an Independent Endpoint Review Committee (IERC) and defined as best response of any of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from date of randomization until disease progression/recurrence (taking smallest measurement recorded since start of treatment as reference). CR: Disappearance of all evidence of target/non-target lesions. PR: At least 30%reduction from baseline in sum of longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD: at least a 20% increase in SLD, taking as reference smallest SLD recorded from baseline/appearance of 1or more new lesions and unequivocal progression of non-target lesions.
HNSCC Efficacy Expansion: Baseline up to Day 1072

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose Escalation and Expansion Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and TEAEs as Per Severity
Time Frame: Up to Day 2511
Adverse event(AE): any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of study drug, whether or not related to study drug. A serious adverse event(SAE) was an AE that resulted in any of following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent events were events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state up to 30 days after last administration.TEAEs included both Serious TEAEs and non-serious TEAEs. Severity of TEAEs were graded using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 toxicity grades, as follows: Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death.
Up to Day 2511
Dose Escalation and Expansion Cohorts: Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs as Per Severity
Time Frame: Baseline up to Day 2511
AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. Treatment-emergent events were the events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state up to 30 days after last administration. TEAEs included both Serious TEAEs and non-serious TEAEs. Treatment related AE was defined as having a "Possible" or "Related" relationship to study treatment, as assessed by the Investigator. Severity of Treatment-Related TEAEs were graded using NCI-CTCAE version 4.0 toxicity grades, as follows: Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death.
Baseline up to Day 2511
Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Area Under Serum Concentration-Time Curve From the Time of Dosing to the Time of the Last Observation (AUC0-t) of Avelumab
Time Frame: Pre-infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48 hours after end of infusion
Area under the serum concentration versus time curve from time zero to the last sampling time t at which the concentration is at or above the lower limit of quantification (LLLQ). AUC(0-t) was calculated according to the mixed log-linear trapezoidal rule.
Pre-infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48 hours after end of infusion
Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC0-infinity) of Avelumab
Time Frame: Pre-infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48 hours after end of infusion
The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
Pre-infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48 hours after end of infusion
Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Maximum Observed Serum Concentration (Cmax) of Avelumab
Time Frame: Pre-infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48 hours after end of infusion
Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve.
Pre-infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48 hours after end of infusion
Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Time to Reach Maximum Observed Serum Concentration (Tmax) of Avelumab
Time Frame: Pre-infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48 hours after end of infusion
Tmax is time to reach maximum observed serum concentration obtained directly from the concentration versus time curve.
Pre-infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48 hours after end of infusion
Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Apparent Terminal Half-Life (t1/2) of Avelumab
Time Frame: Pre-infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48 hours after end of infusion
Apparent terminal half-life was defined as the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination.
Pre-infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48 hours after end of infusion
Dose Expansion Phase: Serum Concentration at End of Infusion (CEOI) of Avelumab
Time Frame: At Day 1, 15, 29, 43, 85, 127 and 169
Serum concentration at end of infusion (CEOI) of Avelumab is reported.
At Day 1, 15, 29, 43, 85, 127 and 169
Dose Expansion Phase: Minimum Serum Post-dose (Ctrough) Concentration of Avelumab
Time Frame: At Day 15, 29, 43, 57, 71, 85, 99, 127 and 169
Serum Ctrough concentration of Avelumab is reported.
At Day 15, 29, 43, 57, 71, 85, 99, 127 and 169
Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Number of Participants With Immune Related Best Overall Response (irBOR) According to Modified Immune-Related Response Criteria (irRC)
Time Frame: Dose Escalation: Baseline up to Day 1023
irBOR defined as best response of any of immune related complete response (irCR), immune related partial response (irPR), immune related stable disease (irSD) and immune related progressive disease (irPD) recorded from baseline until immune related disease progression and determined according to modified irRC per investigator assessment. irCR: Complete disappearance of all tumor lesions (both index and non-index lesions with no new measurable/unmeasurable lesions). irPR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions). irSD: SLD of target and new measurable lesions neither irCR, irPR, or irPD. irPD: SLD of target and new measurable lesions increases greater than or equal to [>=] 20%, confirmed by a repeat, consecutive observations at least 4 weeks from the date first documented. Number of participants with immune-related best overall response in each category (irCR, irPR, irSD, irPD) was reported.
Dose Escalation: Baseline up to Day 1023
Dose Expansion Cohort: Number of Participants With Immune Related Best Overall Response (irBOR) According to Modified Immune-Related Response Criteria (irRC)
Time Frame: Dose Expansion: Baseline up to Day 2023
irBOR defined as best response of any of immune related complete response (irCR), immune related partial response (irPR), immune related stable disease (irSD) and immune related progressive disease (irPD) recorded from baseline until immune related disease progression and determined according to modified irRC per investigator assessment. irCR: Complete disappearance of all tumor lesions (both index and non-index lesions with no new measurable/unmeasurable lesions). irPR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions). irSD: SLD of target and new measurable lesions neither irCR, irPR, or irPD. irPD: SLD of target and new measurable lesions increases greater than or equal to [>=] 20%, confirmed by a repeat, consecutive observations at least 4 weeks from the date first documented. Number of participants with immune-related best overall response in each category (irCR, irPR, irSD, irPD) was reported.
Dose Expansion: Baseline up to Day 2023
Dose Escalation Cohort: Number of Participants With Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time Frame: Dose Escalation: Baseline up to Day 2511
BOR was determined according to RECIST v1.1 and as per investigator assessment. BOR is defined as the best response of any of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from date of randomization until disease progression or recurrence (taking the smallest measurement recorded since start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD =Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Number of participants with best overall response in each category (CR, PR, SD, PD) was reported.
Dose Escalation: Baseline up to Day 2511
Dose Expansion Cohort: Number of Participants With Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time Frame: Dose Expansion: Baseline up to Day 2023
BOR was determined according to RECIST v1.1 and as per investigator assessment. BOR is defined as the best response of any of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from date of randomization until disease progression or recurrence (taking the smallest measurement recorded since start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD = Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Number of participants with best overall response in each category (CR, PR, SD, PD) was reported.
Dose Expansion: Baseline up to Day 2023
Dose Expansion Cohort (Secondary Urothelial Carcinoma Cohort): Number of Participants With Confirmed Best Overall Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 as Adjudicated by an Independent Endpoint Review Committee
Time Frame: Secondary Urothelial Carcinoma Dose Expansion: Baseline up to Day 931
Confirmed Best Overall Response (BOR) was determined according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1and as adjudicated by an Independent Endpoint Review Committee (IERC) is defined as best response of any of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from date of randomization until disease progression/recurrence (taking smallest measurement recorded since start of treatment as reference). CR: Disappearance of all evidence of target/non-target lesions. PR: At least 30% reduction from baseline in sum of longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD: at least a 20% increase in SLD, taking as reference smallest SLD recorded from baseline/appearance of 1or more new lesions and unequivocal progression of non-target lesions. Number of participants with BOR in each category (CR, PR, SD, PD) were reported.
Secondary Urothelial Carcinoma Dose Expansion: Baseline up to Day 931
Dose Expansion Cohort: Progression-Free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Time Frame: Dose Expansion: Baseline up to Day 2023
The PFS time (based on investigator assessments), according to the RECIST 1.1, was defined as the time from first administration of study treatment until first documentation of progressive disease (PD) or death when death occurred within 12 weeks of the last tumor assessment or first administration of study treatment (whichever was later). PD was defined as at least a 20% increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. The analysis of PFS was performed with a Kaplan-Meier method.
Dose Expansion: Baseline up to Day 2023
Dose Expansion Cohort: Immune Related Progression-Free Survival (irPFS) Time According to Modified Immune-Related Response Criteria (irRC)
Time Frame: Dose Expansion: Baseline up to Day 2023
The irPFS time was defined as the time from first administration of study treatment until first documentation of immune-related progressive disease (irPD) or death when death occurred within 12 weeks of the last tumor assessment or first administration of study treatment (whichever was later). irPD: sum of the longest diameters of target and new measurable lesions increases greater than or equal to [>=] 20%, confirmed by a repeat, consecutive observations at least 4 weeks from the date first documented. The analysis of irPFS will be performed with a Kaplan-Meier method. Data for immune related progression-free survival time has been reported.
Dose Expansion: Baseline up to Day 2023
Dose Expansion Cohort: Overall Survival (OS) Time
Time Frame: Dose Expansion: Baseline up to Day 2023
Overall survival time was measured as time in months first administration of trial treatment to death. The analysis of OS time was performed with a Kaplan-Meier method.
Dose Expansion: Baseline up to Day 2023
Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Programmed Death Ligand 1 (PD-L1) Receptor Occupancy
Time Frame: Pre-infusion on Day 1; 48 hours after infusion on Day 3; Pre-infusion on Days 15, 43, and 85
Percentage of PD-L1 receptors occupied by avelumab on human lymphocytes (CD3+ T-cells) was assessed by flow cytometry on peripheral blood mononuclear cell (PBMC) samples. Greater than or equal to [>=] 85 percent [%] of cell viability was required for reliable receptor occupancy assessment.
Pre-infusion on Day 1; 48 hours after infusion on Day 3; Pre-infusion on Days 15, 43, and 85
Dose Expansion Cohort: Number of Participants With Positive Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue
Time Frame: Dose Expansion: Baseline up to Day 2023
PD-L1 assessment was performed using immunohistochemistry. PD-L1 expression status was classified as positive or negative based on the following cut-offs: For tumor cells: Participants were considered PD-L1 expression positive (negative): - if at least (less than) 5% of the tumor cells show PD-L1 membrane staining >= 1+, respectively. This was used as the primary cut-off; - if at least (less than) 25% of the tumor cells show PD-L1 membrane staining >=2+, respectively. This was considered as secondary cut-off; - if at least (less than) 1% of the tumor cells show PD-L1 membrane staining >=1+, respectively. This was used as the tertiary cut-off; - if at least (less than) 50% of the tumor cells show PD-L1 membrane staining >=1+, respectively. This was used as the '50% cut-off'; - if at least (less than) 80% of the tumor cells show PD-L1 membrane staining ≥1+, respectively. This was used as the '80% cut-off'.
Dose Expansion: Baseline up to Day 2023
Primary Expansion Cohorts: Number of Participants With Unconfirmed Response at Week 13 According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time Frame: Week 13
The response criteria evaluation was carried out according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. CR and PR did not need to be confirmed by a subsequent tumor assessment due to blinded central assessment. CR: Disappearance of all target lesions since baseline; PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters; SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR and PD: at least a 20% increase in SLD, taking as reference smallest SLD recorded from baseline/appearance of 1or more new lesions and unequivocal progression of non-target lesions. Number of participants with unconfirmed response at week 13 according to response evaluation criteria in solid tumors (RECIST) version 1.1 were reported.
Week 13
Dose Expansion Cohort: Duration of Response According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Per Investigator Assessment
Time Frame: Dose Expansion: Baseline up to Day 2023
Duration of response according to RECIST 1.1, per investigator assessment was calculated for each participant with a confirmed response (complete response [CR] or partial response [PR]) as the time from the first observation of response to the first observation of documented disease progression (or death within 12 weeks of the last tumor assessment). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Results were calculated based on Kaplan-Meier estimates.
Dose Expansion: Baseline up to Day 2023
Dose Expansion Cohort: Duration of Response According to Modified Immune-Related Response Criteria (irRC) Per Investigator Assessment
Time Frame: Dose Expansion: Baseline up to Day 2023
Duration of response according to modified irRC, per investigator assessment was calculated for each participant with a confirmed response (immune-related complete response [irCR] or immune-related partial response [irPR]) as the time from the first observation of response to the first observation of documented disease progression (or death within 12 weeks of the last tumor assessment). irCR: Complete disappearance of all tumor lesions (both index and non-index lesions with no new measurable/unmeasurable lesions). irPR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions). Results were calculated based on Kaplan-Meier estimates.
Dose Expansion: Baseline up to Day 2023
Efficacy Expansion Cohorts: Duration of Response According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Per Independent Endpoint Review Committee (IERC)
Time Frame: Efficacy Expansion: Baseline up to Day 1072
Duration of response according to modified irRC, per investigator assessment was calculated for each participant with a confirmed response (immune-related complete response [irCR] or immune-related partial response [irPR]) as the time from the first observation of response to the first observation of documented disease progression (or death within 12 weeks of the last tumor assessment). irCR: Complete disappearance of all tumor lesions (both index and non-index lesions with no new measurable/unmeasurable lesions). irPR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions). Results were calculated based on Kaplan-Meier estimates.
Efficacy Expansion: Baseline up to Day 1072
Efficacy Expansion Cohorts: Progression-Free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 as Per Independent Endpoint Review Committee (IERC)
Time Frame: Efficacy Expansion: Baseline up to Day 1072
The PFS time (based on IERC), according to the RECIST 1.1, was defined as the time from first administration of study treatment until first documentation of progressive disease (PD) or death when death occurred within 12 weeks of the last tumor assessment or first administration of study treatment (whichever was later). PD was defined as at least a 20% increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. The analysis of PFS was performed with a Kaplan-Meier method.
Efficacy Expansion: Baseline up to Day 1072
Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Number of Participants With at Least 1 Positive Anti Drug Antibodies (ADA)
Time Frame: Dose Escalation: Baseline up to Day 1023
Serum samples were analyzed by a validated electrochemiluminescence immunoassay to detect the presence of antidrug antibodies (ADA). Number of participants with ADA positive results for Avelumab were reported.
Dose Escalation: Baseline up to Day 1023
Dose Expansion Cohort: Number of Participants With Atleast 1 Positive Anti Drug Antibodies (ADA) Assay
Time Frame: Dose Expansion: Baseline up to Day 2023
Serum samples were analyzed by a validated electrochemiluminescence immunoassay to detect the presence of antidrug antibodies (ADA). Number of participants with ADA positive results for Avelumab were reported.
Dose Expansion: Baseline up to Day 2023

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

EMD Serono Research & Development Institute, Inc.

Collaborators

Merck KGaA, Darmstadt, Germany

Investigators

  • Study Director: Medical Responsible, EMD Serono Inc., an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

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General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 31, 2013

Primary Completion (Actual)

December 16, 2019

Study Completion (Actual)

December 16, 2019

Study Registration Dates

First Submitted

January 14, 2013

First Submitted That Met QC Criteria

January 16, 2013

First Posted (Estimate)

January 21, 2013

Study Record Updates

Last Update Posted (Actual)

December 20, 2021

Last Update Submitted That Met QC Criteria

October 26, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EMR 100070-001
  • 2013-002834-19 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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