A Study of Ladiratuzumab Vedotin in Advanced Solid Tumors

April 15, 2024 updated by: Seagen Inc.

Open-Label Phase 2 Study of Ladiratuzumab Vedotin (LV) for Unresectable Locally Advanced or Metastatic Solid Tumors

This trial will study ladiratuzumab vedotin (LV) alone and with pembrolizumab to find out if it works to treat different types of solid tumors. It will also find out what side effects may occur. A side effect is anything the drug does besides treating cancer.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This trial is designed to assess the antitumor activity, safety, and tolerability of LV alone and with pembrolizumab, for the treatment of solid tumors. Participants with the following advanced solid tumors will be enrolled:

Cohort 1: small cell lung cancer (SCLC) Cohort 2: non-small cell lung cancer-squamous (NSCLC-squamous) Cohort 3: non-small cell lung cancer-nonsquamous (NSCLC-nonsquamous) Cohort 4: head and neck squamous cell carcinoma (HNSCC) Cohort 5: esophageal squamous cell carcinoma (esophageal-squamous) Cohort 6: gastric and gastroesophageal junction (GEJ) adenocarcinoma Cohort 7: castration-resistant prostate cancer (CRPC) Cohort 8: melanoma

Participants will continue to receive study treatment until disease progression, unacceptable toxicity, investigator decision, consent withdrawal, study termination by the sponsor, pregnancy, or death, whichever comes first.

Study Type

Interventional

Enrollment (Actual)

205

Phase

  • Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

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

Study Contact

Study Locations

  • Australia
    • Other
      • Bedford Park, Other, Australia, 5042
        • Flinders Medical Centre
      • Douglas, Other, Australia, 4814
        • Townsville Cancer Center
      • Frankston, Other, Australia, 3199
        • Peninsula and South East Oncology
      • Gosford, Other, Australia, 2250
        • Central Coast Local Health District (Gosford and Wyong Hospitals)
      • Hobart, Other, Australia, 7000
        • Royal Hobart Hospital
      • Malvern, Other, Australia, 3144
        • Cabrini
      • Sydney, Other, Australia, 2010
        • St Vincents Hospital Sydney
      • Wollstonecraft, Other, Australia, 2065
        • Melanoma Institute Australia
  • Italy
    • Other
      • Bologna, Other, Italy, 40138
        • Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi
      • Firenze, Other, Italy, 50134
        • Azienda Ospedaliero Universitaria Careggi
      • Genova, Other, Italy, 16125
        • ASL 3 Genovese Villa Scassi Hospital
      • Lucca, Other, Italy, 55100
        • San Luca Hospital
      • Meldola, Other, Italy, 47014
        • IRCCS IRST
      • Milan, Other, Italy, 20162
        • Niguarda Ca' Granda Hospital
      • Milano, Other, Italy, 20141
        • Istituto Europeo di Oncologia
      • Monza, Other, Italy, 20900
        • Fondazione IRCCS San Gerardo dei Tintori
      • Napoli, Other, Italy, 80131
        • Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
      • Roma, Other, Italy, 00168
        • Policlinico Universitario Agostino Gemelli
      • Siena, Other, Italy, 53100
        • AOUS Policlinico Le Scotte
  • Korea, Republic of
    • Other
      • Busan, Other, Korea, Republic of, 49201
        • Dong-A University Hospital
      • Hwasun, Other, Korea, Republic of, 58128
        • Chonnam National University Hwasun Hospital
      • Seongnam-si, Other, Korea, Republic of, 13605
        • Seoul National University Bundang Hospital
      • Seoul, Other, Korea, Republic of, 03080
        • Seoul National University Hospital
      • Seoul, Other, Korea, Republic of, 06351
        • Samsung Medical Center
      • Seoul, Other, Korea, Republic of, 07671
        • Seoul National University Boramae Medical Center
      • Seoul, Other, Korea, Republic of, 03722
        • Severance Hospital, Yonsei University Health System
      • Seoul, Other, Korea, Republic of, 152-703/08308
        • Korea University Guro Hospital
      • Suwon-si, Other, Korea, Republic of, 16247
        • St. Vincent's Hospital, The Catholic University of Korea
      • Suwon-si, Other, Korea, Republic of, 16499
        • Ajou University Hospital
  • Taiwan
    • Other
      • Taichung, Other, Taiwan, 40705
        • Taichung Veterans General Hospital
      • Tainan, Other, Taiwan, 70403
        • National Cheng-Kung University Hospital
      • Taipei, Other, Taiwan, 10002
        • National Taiwan University Hospital
      • Taipei, Other, Taiwan, 110
        • Taipei Medical University Hospital
  • United Kingdom
    • Other
      • Glasgow, Other, United Kingdom, G12 0YN
        • The Beatson West of Scotland Cancer Centre
      • London, Other, United Kingdom, SW3 6JJ
        • The Royal Marsden Hospital
      • London, Other, United Kingdom, W1G 6AD
        • Sarah Cannon Research Institute UK
      • London, Other, United Kingdom, WC1E6DD
        • UCL Cancer Institute
      • Manchester, Other, United Kingdom, M20 4BX
        • The Christie NHS Foundation Trust
      • Sutton, Other, United Kingdom, SM2 5PT
        • The Royal Marsden Hospital (Surrey)
  • United States
    • Arizona
      • Chandler, Arizona, United States, 85224
        • Ironwood Cancer & Research Centers - Chandler
    • California
      • Los Angeles, California, United States, 90033
        • Adventist Health White Memorial
      • Santa Rosa, California, United States, 95403
        • Providence Medical Foundation
    • Connecticut
      • Norwich, Connecticut, United States, 06360
        • Eastern CT Hematology and Oncology Associates
    • Florida
      • Jacksonville, Florida, United States, 32204
        • GenesisCare USA
      • Orlando, Florida, United States, 32804
        • AdventHealth Cancer Institute
    • Georgia
      • Columbus, Georgia, United States, 31904
        • IACT Health
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital - Illinois
    • Indiana
      • Fort Wayne, Indiana, United States, 46804
        • Fort Wayne Medical Oncology and Hematology
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Comprehensive Cancer Center
    • Minnesota
      • Saint Louis Park, Minnesota, United States, 55416
        • HealthPartners Institute
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Comprehensive Cancer Centers of Nevada
    • New Jersey
      • Paramus, New Jersey, United States, 07652
        • Valley Hospital, The / Luckow Pavilion
    • New Mexico
      • Farmington, New Mexico, United States, 87401
        • San Juan Oncology Associates
    • New York
      • New York, New York, United States, 10065
        • Weill Cornell Medicine
      • Stony Brook, New York, United States, 11794-7263
        • Stony Brook University Cancer Center
    • North Carolina
      • Pinehurst, North Carolina, United States, 28374
        • FirstHealth of the Carolinas
    • Ohio
      • Canton, Ohio, United States, 44718
        • Gabrail Cancer Center Research, LLC
    • Oregon
      • Portland, Oregon, United States, 97213
        • Providence Portland Medical Center
    • South Carolina
      • Greenville, South Carolina, United States, 29601
        • Saint Francis Hospital / Bon Secours - South Carolina
    • Tennessee
      • Chattanooga, Tennessee, United States, 37403
        • Erlanger Oncology and Hematology
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology-Nashville/Sarah Cannon Research Institute
    • Texas
      • Lubbock, Texas, United States, 79410
        • Joe Arrington Cancer Research and Treatment Center
      • Tyler, Texas, United States, 75701
        • UT Health East Texas HOPE Cancer Center
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Carbone Cancer Center / University of Wisconsin

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

Description

Inclusion Criteria

  • All Cohorts

    • Measurable disease according to RECIST v1.1 as assessed by the investigator
    • Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1

  • Cohort 1: SCLC (Parts A and B)

    • Must have extensive stage disease
    • Must have disease progression during or following prior platinum-based systemic chemotherapy for extensive stage disease;
    • No more than 1 prior line of cytotoxic chemotherapy for extensive disease stage
    • May have received prior anti-PD(L)1 therapy

  • Cohort 2: NSCLC-squamous (Parts A and B)

    • Must have unresectable locally advanced or metastatic disease

    • Must have disease progression during or following systemic therapy

      • Participants must have progressed during or after a platinum-based combination therapy administered for the treatment of metastatic disease, OR
      • Participants must have progressed within 6 months of last dose of platinum-based adjuvant, neoadjuvant, or definitive chemotherapy, or concomitant chemoradiation regimen for early stage or locally advanced stage disease.
    • Participants with known epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), reactive oxygen species (ROS), BRAF, or other actionable mutations are not eligible
    • No more than 1 prior line of cytotoxic chemotherapy for their advanced disease
    • Must have received prior anti-PD(L)1 therapy, unless contraindicated

  • Cohort 3: NSCLC-nonsquamous (Parts A and B)

    • Must have unresectable locally advanced or metastatic disease

    • Must have disease progression during or following systemic therapy

      • Participants must have progressed during or after a platinum-based combination therapy administered for the treatment of metastatic disease, OR
      • Participants must have progressed within 6 months of last dose of platinum-based adjuvant, neoadjuvant, or definitive chemotherapy, or concomitant chemoradiation regimen for early stage or locally advanced state disease.
    • Participants with known EGFR, ALK, ROS, BRAF, tropomyosin receptor kinase (TRK), or other actionable mutations are not eligible
    • Must have had prior platinum-based chemotherapy
    • No more than 1 prior line of cytotoxic chemotherapy for their advanced disease
    • Must have received prior anti-PD(L)1 therapy, unless contraindicated

  • Cohort 4: HNSCC (Parts A and B)

    • Must have unresectable locally recurrent or metastatic disease

      • Must have disease progression during or following prior line of systemic therapy
      • Disease progression after treatment with a platinum-containing regimen for recurrent/metastatic disease; OR
      • Recurrence/progression within 6 months of last dose of platinum therapy given as part of a multimodal therapy in the curative setting
    • No more than 1 line of cytotoxic chemotherapy for their advanced disease
    • May have received prior anti-PD(L)1 therapy, unless contraindicated

  • Cohort 5: esophageal-squamous (Parts A and B)

    • Must have unresectable locally advanced or metastatic disease
    • Must have disease progression during or following systemic therapy
    • Must have had prior platinum-based chemotherapy
    • No more than 1 line of cytotoxic chemotherapy for their advanced disease

  • Cohort 6: gastric and GEJ adenocarcinoma (Parts A and B)

    • Must have unresectable locally advanced or metastatic disease
    • Must have received prior platinum-based therapy
    • Must have disease progression during or following systemic therapy
    • Participants with known human epidermal growth factor receptor 2 (HER2) overexpression must have received prior HER2-targeted therapy
    • No more than 1 line of prior cytotoxic chemotherapy for their advanced disease
    • Participants may have received prior anti-PD(L)1 therapy, unless contraindicated

  • Cohort 7: CRPC (Part B only)

    • Must have histologically or cytologically confirmed adenocarcinoma of the prostate

      • Participants with components of small cell of neuroendocrine histology are excluded
    • Must have metastatic castration-resistant disease
    • Must have been ≥28 days between cessation of androgen receptor-targeted therapy and start of study treatment
    • Must have received no more than 1 prior line of androgen receptor-targeted therapy for metastatic castration-sensitive prostate cancer or CRPC

    • No prior cytotoxic chemotherapy in the metastatic CRPC setting

      • For participants who received cytotoxic chemotherapy in CSPC, at least 6 months must have elapsed between last dose of chemotherapy and start of study treatment
      • No more than 1 prior line of cytotoxic chemotherapy for CSPC

    • Participants with measurable disease are eligible if the following criteria are met:

      • A minimum starting PSA level ≥1.0 ng/mL
      • Participants with measurable soft tissue disease must have evidence of measurable soft tissue disease according to PCWG3 criteria.
    • Participants with known breast cancer gene (BRCA) mutations are excluded
    • No prior radioisotope therapy or radiotherapy to ≥30% of bone marrow

  • Cohort 8: Melanoma (Parts B and C)

    • Must have histologically or cytologically confirmed cutaneous malignant melanoma

      • Participants with mucosal, acral, or uveal melanoma are excluded
    • Must have locally advanced unresectable or metastatic stage disease
    • Must have progressive disease following anti-PD(L)1 therapy
    • Must have received BRAF +/- MEK inhibitor therapy if BRAF mutated (Part C)

Exclusion Criteria

  • Active concurrent malignancy or a previous malignancy within the past 3 years
  • Any anticancer therapy within 3 weeks of starting study treatment. Participants who are/were on adjuvant hormonal therapy for the treatment of malignancies with negligible risk of metastases are eligible.
  • Known active central nervous system lesions
  • Any ongoing clinically significant toxicity associated with prior treatment (Grade 2 or higher)
  • Ongoing sensory or motor neuropathy of Grade ≥2
  • Has received prior radiotherapy within 2 weeks of start of study treatment
  • History of interstitial lung disease.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A: Non-randomized LV monotherapy
Monotherapy dosing schedule 1.
Drug: ladiratuzumab vedotin
Intravenous (into the vein; IV) infusion
Other Names:
  • SGN-LIV1A
Experimental: Part B: Non-randomized LV monotherapy
Monotherapy dosing schedule 2.
Drug: ladiratuzumab vedotin
Intravenous (into the vein; IV) infusion
Other Names:
  • SGN-LIV1A
Experimental: Part C - Arm 1: Randomized LV monotherapy
Monotherapy dosing schedule 3.
Drug: ladiratuzumab vedotin
Intravenous (into the vein; IV) infusion
Other Names:
  • SGN-LIV1A
Experimental: Part C - Arm 2: Randomized LV combination therapy
Combination dosing schedule 1.
Drug: ladiratuzumab vedotin
Intravenous (into the vein; IV) infusion
Other Names:
  • SGN-LIV1A
Drug: pembrolizumab
200mg given by IV on Day 1 of each 21-day cycle
Other Names:
  • Keytruda
Experimental: Part C - Arm 3: Randomized LV combination therapy
Combination dosing schedule 2.
Drug: ladiratuzumab vedotin
Intravenous (into the vein; IV) infusion
Other Names:
  • SGN-LIV1A
Drug: pembrolizumab
200mg given by IV on Day 1 of each 21-day cycle
Other Names:
  • Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Confirmed objective response rate (ORR) as determined by investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
Time Frame: Up to approximately 1 year
Confirmed ORR is defined as the proportion of participants who achieve a confirmed complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by the investigator.
Up to approximately 1 year
Prostate-specific antigen (PSA) response rate as determined by investigator according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria (Cohort 7 only)
Time Frame: Up to approximately 1 year
Confirmed PSA response rate is defined as the proportion of participants with a reduction from baseline PSA level of at least 50%, measured twice ≥3 weeks apart.
Up to approximately 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of response (DOR) as determined by investigator according to RECIST v1.1
Time Frame: Up to approximately 1 year
DOR is defined as the time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of progressive disease (PD) or death due to any cause, whichever comes first.
Up to approximately 1 year
PSA-DOR as determined by investigator assessment (Cohort 7 only)
Time Frame: Up to approximately 1 year
PSA-DOR is defined as the time from the first documentation of PSA response to the first documentation of PSA progression or death, whichever comes first
Up to approximately 1 year
PSA-PFS as determined by investigator assessment (Cohort 7 only)
Time Frame: Up to approximately 1 year
PSA-PFS is defined as the time from the start of study treatment to first occurrence of PSA progression or death, whichever comes first
Up to approximately 1 year
Overall survival (OS)
Time Frame: Up to approximately 1 year
OS is defined as the time from the start of study treatment to date of death due to any cause.
Up to approximately 1 year
Maximum observed concentration (Cmax)
Time Frame: Up to approximately 1 year
Pharmacokinetic (PK) endpoint of LV
Up to approximately 1 year
Area under the concentration-time curve (AUC)
Time Frame: Up to approximately 1 year
PK endpoint of LV
Up to approximately 1 year
Incidence of antitherapeutic antibodies (ATAs) to LV
Time Frame: Up to approximately 1 year
Up to approximately 1 year
Number of participants with adverse events (AEs)
Time Frame: Up to approximately 1 year
An AE is any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Up to approximately 1 year
Disease control rate (DCR) as determined by investigator according to RECIST v1.1
Time Frame: Up to approximately 1 year
DCR is defined as the proportion of participants who achieve a confirmed CR or PR according to RECIST v1.1 as assessed by the investigator, or meet the stable disease (SD) criteria at least once after start of study treatment at a minimum interval of 5 weeks or 7 weeks for prostate cancer subjects.
Up to approximately 1 year
Progression-free survival (PFS) as determined by investigator according to RECIST v1.1
Time Frame: Up to approximately 1 year
PFS is defined as the time from the start of study treatment to the first documentation of PD by RECIST v1.1 or clinical PD or by PSA progression (prostate cancer cohort) or death due to any cause, whichever comes first.
Up to approximately 1 year

Collaborators and Investigators

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

Sponsor

Seagen Inc.

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Brandon Croft, PharmD, Seagen Inc.

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)

October 9, 2019

Primary Completion (Actual)

November 28, 2023

Study Completion (Actual)

November 28, 2023

Study Registration Dates

First Submitted

July 23, 2019

First Submitted That Met QC Criteria

July 23, 2019

First Posted (Actual)

July 25, 2019

Study Record Updates

Last Update Posted (Actual)

April 17, 2024

Last Update Submitted That Met QC Criteria

April 15, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SGNLVA-005

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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