A Study to Assess the Safety and Pharmacokinetics of MOXR0916 and Atezolizumab (Also Known as MPDL3280A or Anti-PD-L1) in Participants With Locally Advanced or Metastatic Solid Tumors

A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of MOXR0916 and Atezolizumab in Patients With Locally Advanced or Metastatic Solid Tumors

This Phase Ib, open-label, dose-escalation study will evaluate the safety, tolerability, and pharmacokinetics of the combination of MOXR0916 and atezolizumab in participants with locally advanced, recurrent, or metastatic incurable solid malignancy that has progressed after available standard therapy; or for which standard therapy has proven to be ineffective or intolerable or is considered inappropriate; or for which a clinical trial of an investigational agent is a recognized standard of care. Participants will be enrolled in two stages: a dose-escalation stage and an expansion stage.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 [PD-L1] antibody; Drug: MOXR0916, a humanized agonist anti-OX40 monoclonal antibody

• Study Type: Interventional
• Enrollment (Actual): 610
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
• Belgium
  • Anderlecht, Belgium, 1070
    • Institut Jules Bordet
  • Gent, Belgium, 9000
    • UZ Gent
  • Wilrijk, Belgium, 2610
    • Sint Augustinus Wilrijk
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network; Princess Margaret Hospital; Medical Oncology Dept
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
• France
  • Villejuif CEDEX, France, 94800
    • Gustave Roussy
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 120-752
    • Yonsei University Health System/Severance Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28050
    • Hosp de Madrid Norte Sanchinarro; Centro Integral; Onco Clara Campal
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria de Navarra
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute - Bisgrove
  • Colorado
    • Aurora, Colorado, United States, 80045-2517
      • University of Colorado
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale School of Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center Lombardi Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University Of Chicago Medical Center; Section Of Hematology/Oncology
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Can Ins
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

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:

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Life expectancy of at least 12 weeks
• Adequate hematologic and end organ function
• Histologic documentation of locally advanced, recurrent, or metastatic incurable solid malignancy that has progressed after available standard therapy; or for which standard therapy is ineffective, intolerable, or considered inappropriate; or for which a clinical trial of an investigational agent is recognized standard of care
• Tumor specimen availability
• Measurable disease according to RECIST v1.1

Exclusion Criteria:

• Any anti-cancer therapy, whether investigational or approved, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment
• Malignancies other than disease under study within 5 years prior to D1 of C1
• Primary central nervous system (CNS) malignancy, or untreated/active CNS metastases
• History of leptomeningeal disease
• History of idiopathic pulmonary fibrosis, pneumonitis (including drug-induced), organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted
• History of autoimmune disease
• Positive human immunodeficiency virus test result
• Active hepatitis B, hepatitis C, or tuberculosis
• Severe infection within 4 weeks prior to D1 of C1
• Prior allogeneic bone marrow or solid organ transplantation
• Significant cardiovascular disease
• Known clinically significant liver disease

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation: MOXR0916 + Atezolizumab; Cohorts of at least 3 participants each will be treated at escalating doses of MOXR0916 in combination with a fixed dose of atezolizumab to determine the MTD or maximum administered dose (MAD).	Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 [PD-L1] antibody; Atezolizumab will be administered intravenously.; Other Names: Tecentriq; Drug: MOXR0916, a humanized agonist anti-OX40 monoclonal antibody; MOXR0916 will be administered intravenously.
Experimental: Expansion: MOXR0916 + Atezolizumab; Approximately 250-580 participants will be enrolled in the expansion stage to better characterize the safety, tolerability, pharmacokinetic variability, biomarkers of anti-tumor activity, and preliminary efficacy of MOXR0916 + atezolizumab in different cancer types.	Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 [PD-L1] antibody; Atezolizumab will be administered intravenously.; Other Names: Tecentriq; Drug: MOXR0916, a humanized agonist anti-OX40 monoclonal antibody; MOXR0916 will be administered intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Dose-Limiting Toxicities (DLTs)	Days (D) 1-21 of Cycle (C) 1 (cycle = 21 days); up to D42 if extended monitoring warranted
Number of Participants with Adverse Events Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 4.0	Baseline until 90 days after last dose or initiation of another systemic anti-cancer therapy, whichever occurs first (up to 3 years)

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Tolerated Dose (MTD) of MOXR0916	Up to 1 year
Recommended Phase II Dose (RP2D) of MOXR0916	Up to 1 year
Percentage of Participants with Anti-MOXR0916 and Anti-Atezolizumab Antibodies	Up to 120 days after the treatment discontinuation visit
Number of Cycles Received with MOXR0916	Baseline until treatment discontinuation (up to 3 years)
Dose Intensity of MOXR0916	Baseline until treatment discontinuation (up to 3 years)
Area under the Concentration-Time Curve (AUC) of MOXR0916	Up to 120 days after the treatment discontinuation visit
Serum Maximum Observed Concentration (Cmax) of MOXR0916	Up to 120 days after the treatment discontinuation visit
Serum Minimum Observed Concentration (Cmin) of MOXR0916	Up to 120 days after the treatment discontinuation visit
Clearance (CL) of MOXR0916	Up to 120 days after the treatment discontinuation visit
Volume of Distribution at Steady State (Vss) of MOXR0916	Up to 120 days after the treatment discontinuation visit
Serum Cmax of Atezolizumab	Up to 120 days after the treatment discontinuation visit
Serum Cmin of Atezolizumab	Up to 120 days after the treatment discontinuation visit
Percentage of Participants with Objective Response Determined Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Baseline until disease progression (up to 3 years)
Duration of Objective Response (DOR) Determined Using RECIST v1.1	From first objective response until death or relapse per RECIST v1.1, whichever occurs first (up to 3 years)
Progression-Free Survival (PFS) Determined Using RECIST v1.1	Baseline until death or disease progression per RECIST v1.1, whichever occurs first (up to 3 years)
Percentage of Participants with Objective Response Determined Using Modified RECIST	Baseline until disease progression (up to 3 years)
DOR Determined Using Modified RECIST	From first objective response until death or relapse per RECIST v1.1, whichever occurs first (up to 3 years)
PFS Determined Using Modified RECIST	Baseline until death or disease progression per RECIST v1.1, whichever occurs first (up to 3 years)
Overall Survival (OS)	Baseline until death (up to 3 years)

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2015
• Primary Completion (Actual): November 22, 2019
• Study Completion (Actual): November 22, 2019

Study Registration Dates

• First Submitted: April 2, 2015
• First Submitted That Met QC Criteria: April 2, 2015
• First Posted (Estimate): April 7, 2015

Study Record Updates

• Last Update Posted (Actual): April 1, 2022
• Last Update Submitted That Met QC Criteria: March 31, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Atezolizumab
• Other Study ID Numbers: GO29674; 2015-000516-18 (EudraCT Number)