A Study of Ladiratuzumab Vedotin in Advanced Solid Tumors

NCT ID: NCT04032704

Last Updated: 2025-03-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 205 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-09
• Study Completion Date: 2023-11-28

Brief Summary

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.

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.

Conditions

Small Cell Lung Cancer; Non-small Cell Lung Cancer, Squamous; Non-small Cell Lung Cancer, Non-squamous; Head and Neck Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Prostate Cancer; Melanoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A: Non-randomized LV monotherapy

Monotherapy dosing schedule 1.

Group Type: EXPERIMENTAL

ladiratuzumab vedotin

Intervention Type: DRUG

Intravenous (into the vein; IV) infusion

Part B: Non-randomized LV monotherapy

Monotherapy dosing schedule 2.

Group Type: EXPERIMENTAL

ladiratuzumab vedotin

Intervention Type: DRUG

Intravenous (into the vein; IV) infusion

Part C - Arm 1: Randomized LV monotherapy

Monotherapy dosing schedule 3.

Group Type: EXPERIMENTAL

ladiratuzumab vedotin

Intervention Type: DRUG

Intravenous (into the vein; IV) infusion

Part C - Arm 2: Randomized LV combination therapy

Combination dosing schedule 1.

Group Type: EXPERIMENTAL

ladiratuzumab vedotin

Intervention Type: DRUG

Intravenous (into the vein; IV) infusion

pembrolizumab

Intervention Type: DRUG

200mg given by IV on Day 1 of each 21-day cycle

Part C - Arm 3: Randomized LV combination therapy

Combination dosing schedule 2.

Group Type: EXPERIMENTAL

ladiratuzumab vedotin

Intervention Type: DRUG

Intravenous (into the vein; IV) infusion

pembrolizumab

Intervention Type: DRUG

200mg given by IV on Day 1 of each 21-day cycle

Interventions

ladiratuzumab vedotin

Intravenous (into the vein; IV) infusion

Intervention Type: DRUG

pembrolizumab

200mg given by IV on Day 1 of each 21-day cycle

Intervention Type: DRUG

Other Intervention Names

SGN-LIV1A; Keytruda

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Seagen Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

Ironwood Cancer & Research Centers - Chandler

Chandler, Arizona, United States

Adventist Health White Memorial

Los Angeles, California, United States

Providence Medical Foundation

Santa Rosa, California, United States

Eastern CT Hematology and Oncology Associates

Norwich, Connecticut, United States

GenesisCare USA

Jacksonville, Florida, United States

AdventHealth Cancer Institute

Orlando, Florida, United States

IACT Health

Columbus, Georgia, United States

Northwestern University

Chicago, Illinois, United States

Decatur Memorial Hospital - Illinois

Decatur, Illinois, United States

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, United States

University of Maryland

Baltimore, Maryland, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

HealthPartners Institute

Saint Louis Park, Minnesota, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Valley Hospital, The / Luckow Pavilion

Paramus, New Jersey, United States

San Juan Oncology Associates

Farmington, New Mexico, United States

Weill Cornell Medicine

New York, New York, United States

Stony Brook University Cancer Center

Stony Brook, New York, United States

FirstHealth of the Carolinas

Pinehurst, North Carolina, United States

Gabrail Cancer Center Research, LLC

Canton, Ohio, United States

Providence Portland Medical Center

Portland, Oregon, United States

Saint Francis Hospital / Bon Secours - South Carolina

Greenville, South Carolina, United States

Erlanger Oncology and Hematology

Chattanooga, Tennessee, United States

Tennessee Oncology-Nashville/Sarah Cannon Research Institute

Nashville, Tennessee, United States

Joe Arrington Cancer Research and Treatment Center

Lubbock, Texas, United States

UT Health East Texas Hope Cancer Center

Tyler, Texas, United States

Carbone Cancer Center / University of Wisconsin

Madison, Wisconsin, United States

Flinders Medical Centre

Bedford Park, Other, Australia

Townsville Cancer Center

Douglas, Other, Australia

Peninsula and South East Oncology

Frankston, Other, Australia

Central Coast Local Health District (Gosford and Wyong Hospitals)

Gosford, Other, Australia

Royal Hobart Hospital

Hobart, Other, Australia

Cabrini

Malvern, Other, Australia

St Vincents Hospital Sydney

Sydney, Other, Australia

Melanoma Institute Australia

Wollstonecraft, Other, Australia

Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi

Bologna, Other, Italy

Azienda Ospedaliero Universitaria Careggi

Florence, Other, Italy

ASL 3 Genovese Villa Scassi Hospital

Genova, Other, Italy

San Luca Hospital

Lucca, Other, Italy

Irccs Irst

Meldola, Other, Italy

Niguarda Ca' Granda Hospital

Milan, Other, Italy

Istituto Europeo di Oncologia

Milan, Other, Italy

Fondazione IRCCS San Gerardo dei Tintori

Monza, Other, Italy

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

Napoli, Other, Italy

Policlinico Universitario Agostino Gemelli

Roma, Other, Italy

AOUS Policlinico Le Scotte

Siena, Other, Italy

Dong-A University Hospital

Busan, Other, South Korea

Chonnam National University Hwasun Hospital

Hwasun, Other, South Korea

Seoul National University Bundang Hospital

Seongnam-si, Other, South Korea

Seoul National University Hospital

Seoul, Other, South Korea

Severance Hospital, Yonsei University Health System

Seoul, Other, South Korea

Samsung Medical Center

Seoul, Other, South Korea

Seoul National University Boramae Medical Center

Seoul, Other, South Korea

Korea University Guro Hospital

Seoul, Other, South Korea

St. Vincent's Hospital, The Catholic University of Korea

Suwon, Other, South Korea

Ajou University Hospital

Suwon, Other, South Korea

Taichung Veterans General Hospital

Taichung, Other, Taiwan

National Cheng-Kung University Hospital

Tainan City, Other, Taiwan

National Taiwan University Hospital

Taipei, Other, Taiwan

Taipei Medical University Hospital

Taipei, Other, Taiwan

The Beatson West of Scotland Cancer Centre

Glasgow, Other, United Kingdom

The Royal Marsden Hospital

London, Other, United Kingdom

Sarah Cannon Research Institute UK

London, Other, United Kingdom

UCL Cancer Institute

London, Other, United Kingdom

The Christie NHS Foundation Trust

Manchester, Other, United Kingdom

The Royal Marsden Hospital (Surrey)

Sutton, Other, United Kingdom

Countries

United States; Australia; Italy; South Korea; Taiwan; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SGNLVA-005

Identifier Type: -

Identifier Source: org_study_id