A Study of Ladiratuzumab Vedotin in Advanced Solid Tumors

NCT04032704 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: SGNLVA-005
• Study Type: interventional
• Target: 205
• Locations: 6 countries
• Sites: 66

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.

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

Keywords

SCLC; NSCLC-squamous; NSCLC-nonsquamous; HNSCC; GEJ adenocarcinoma; Seattle Genetics

Outcome Measures

Primary Outcomes (3)

• Part A: Confirmed Objective Response Rate (ORR) as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

  Confirmed ORR was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than (\<) 10 millimeter (mm). PR was defined as more than or equal to (\>=) 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants who did not have at least 2 post-baseline response assessment (initial response and confirmation scan) were counted as non-responders.

  From the first dose of study treatment until the first documented CR or PR or new anticancer therapies or death, whichever occurred first (maximum up to 8.3 months)

• Part B: Confirmed ORR as Determined by Investigator According to RECIST v1.1

  Confirmed ORR was defined as the percentage of participants with a confirmed CR or PR per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR was defined as \>= 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants who did not have at least 2 post-baseline response assessment (initial response and confirmation scan) were counted as non-responders.

  From the first dose of study treatment until the first documented CR or PR or new anticancer therapies or death, whichever occurred first (maximum up to 34.7 months for 1.25 mg/kg and 5.7 months for 1 mg/kg dose level)

• Part B: Confirmed Prostate-Specific Antigen (PSA) Response Rate as Determined by Investigator According to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) Criteria, for Prostate Cancer

  Confirmed PSA response rate was defined as the percentage of participants with a reduction from baseline PSA level of at least 50%, measured twice \>= 3 weeks apart. PSA progression was defined as per PCWG3 criteria- a) if a participant presented first a decline from baseline, progression was defined as the first PSA increase that was \>=25% and \>=2 nanograms per milliliter (ng/mL) above the nadir, and which was confirmed by a consecutive second value \>=3 weeks later that fulfilled the same criteria (that is, a confirmed rising trend); b) if a participant did not present a decline from baseline, progression was defined as the first PSA increase that was \>=25% and \>=2 ng/mL increased from baseline beyond 12 weeks.

  From the first dose of study treatment up to the date of last response assessment (maximum up to 13.5 months)

Secondary Outcomes (26)

• Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Treatment Related TEAEs and >= Grade 3 TEAE

  From start of study treatment up to 30 days after last dose of study treatment (maximum up to 37.5 months)

• Part B: Number of Participants With TEAEs, TESAEs, Treatment Related TEAEs and >= Grade 3 TEAE

  From start of study treatment up to 30 days after last dose of study treatment (maximum up to 37.5 months)

• Part A: Confirmed Investigator Determined Disease Control Rate (DCR) According to RECIST v1.1

  From the first dose of study treatment until the first documented CR, PR or SD or new anticancer therapies or death, whichever occurred first (maximum up to 4.1 months)

• Part B: Confirmed Investigator Determined DCR According to RECIST v1.1

  From the first dose of study treatment until the first documented CR, PR or SD or new anticancer therapies or death, whichever occurred first (maximum up to 5.5 months for 1.25 mg/kg and 1.5 months for 1 mg/kg dose level)

• Part A: Confirmed Investigator Determined Duration of Response (DOR) According to RECIST v1.1

  From the first documentation of CR or PR to PD or death or censoring whichever occurred first (maximum up to 5.7 months)

Study Arms (5)

Part A: Non-randomized LV monotherapy

EXPERIMENTAL

Monotherapy dosing schedule 1.

Drug: ladiratuzumab vedotin

Part B: Non-randomized LV monotherapy

EXPERIMENTAL

Monotherapy dosing schedule 2.

Drug: ladiratuzumab vedotin

Part C - Arm 1: Randomized LV monotherapy

EXPERIMENTAL

Monotherapy dosing schedule 3.

Drug: ladiratuzumab vedotin

Part C - Arm 2: Randomized LV combination therapy

EXPERIMENTAL

Combination dosing schedule 1.

Drug: ladiratuzumab vedotin; Drug: pembrolizumab

Part C - Arm 3: Randomized LV combination therapy

EXPERIMENTAL

Combination dosing schedule 2.

Drug: ladiratuzumab vedotin; Drug: pembrolizumab

Interventions

ladiratuzumab vedotin DRUG

Intravenous (into the vein; IV) infusion

Also known as: SGN-LIV1A

Part A: Non-randomized LV monotherapy; Part B: Non-randomized LV monotherapy; Part C - Arm 1: Randomized LV monotherapy; Part C - Arm 2: Randomized LV combination therapy; Part C - Arm 3: Randomized LV combination therapy

pembrolizumab DRUG

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

Also known as: Keytruda

Part C - Arm 2: Randomized LV combination therapy; Part C - Arm 3: Randomized LV combination therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Seagen Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (66)

Ironwood Cancer & Research Centers - Chandler

Chandler, Arizona, 85224, United States

Location

Adventist Health White Memorial

Los Angeles, California, 90033, United States

Location

Providence Medical Foundation

Santa Rosa, California, 95403, United States

Location

Eastern CT Hematology and Oncology Associates

Norwich, Connecticut, 06360, United States

Location

GenesisCare USA

Jacksonville, Florida, 32204, United States

Location

AdventHealth Cancer Institute

Orlando, Florida, 32804, United States

Location

IACT Health

Columbus, Georgia, 31904, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Decatur Memorial Hospital - Illinois

Decatur, Illinois, 62526, United States

Location

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, 46804, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

HealthPartners Institute

Saint Louis Park, Minnesota, 55416, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Valley Hospital, The / Luckow Pavilion

Paramus, New Jersey, 07652, United States

Location

San Juan Oncology Associates

Farmington, New Mexico, 87401, United States

Location

Weill Cornell Medicine

New York, New York, 10065, United States

Location

Stony Brook University Cancer Center

Stony Brook, New York, 11794-7263, United States

Location

FirstHealth of the Carolinas

Pinehurst, North Carolina, 28374, United States

Location

Gabrail Cancer Center Research, LLC

Canton, Ohio, 44718, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Saint Francis Hospital / Bon Secours - South Carolina

Greenville, South Carolina, 29601, United States

Location

Erlanger Oncology and Hematology

Chattanooga, Tennessee, 37403, United States

Location

Tennessee Oncology-Nashville/Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Joe Arrington Cancer Research and Treatment Center

Lubbock, Texas, 79410, United States

Location

UT Health East Texas Hope Cancer Center

Tyler, Texas, 75701, United States

Location

Carbone Cancer Center / University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Flinders Medical Centre

Bedford Park, Other, 5042, Australia

Location

Townsville Cancer Center

Douglas, Other, 4814, Australia

Location

Peninsula and South East Oncology

Frankston, Other, 3199, Australia

Location

Central Coast Local Health District (Gosford and Wyong Hospitals)

Gosford, Other, 2250, Australia

Location

Royal Hobart Hospital

Hobart, Other, 7000, Australia

Location

Cabrini

Malvern, Other, 3144, Australia

Location

St Vincents Hospital Sydney

Sydney, Other, 2010, Australia

Location

Melanoma Institute Australia

Wollstonecraft, Other, 2065, Australia

Location

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

Bologna, Other, 40138, Italy

Location

Azienda Ospedaliero Universitaria Careggi

Florence, Other, 50134, Italy

Location

ASL 3 Genovese Villa Scassi Hospital

Genova, Other, 16125, Italy

Location

San Luca Hospital

Lucca, Other, 55100, Italy

Location

Irccs Irst

Meldola, Other, 47014, Italy

Location

Niguarda Ca' Granda Hospital

Milan, Other, 20162, Italy

Location

Istituto Europeo di Oncologia

Milan, Other, 20141, Italy

Location

Fondazione IRCCS San Gerardo dei Tintori

Monza, Other, 20900, Italy

Location

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

Napoli, Other, 80131, Italy

Location

Policlinico Universitario Agostino Gemelli

Roma, Other, 00168, Italy

Location

AOUS Policlinico Le Scotte

Siena, Other, 53100, Italy

Location

Dong-A University Hospital

Busan, Other, 49201, South Korea

Location

Chonnam National University Hwasun Hospital

Hwasun, Other, 58128, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, Other, 13605, South Korea

Location

Seoul National University Hospital

Seoul, Other, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, Other, 03722, South Korea

Location

Samsung Medical Center

Seoul, Other, 06351, South Korea

Location

Seoul National University Boramae Medical Center

Seoul, Other, 07671, South Korea

Location

Korea University Guro Hospital

Seoul, Other, 152-703/08308, South Korea

Location

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

Suwon, Other, 16247, South Korea

Location

Ajou University Hospital

Suwon, Other, 16499, South Korea

Location

Taichung Veterans General Hospital

Taichung, Other, 40705, Taiwan

Location

National Cheng-Kung University Hospital

Tainan, Other, 70403, Taiwan

Location

National Taiwan University Hospital

Taipei, Other, 10002, Taiwan

Location

Taipei Medical University Hospital

Taipei, Other, 110, Taiwan

Location

The Beatson West of Scotland Cancer Centre

Glasgow, Other, G12 0YN, United Kingdom

Location

The Royal Marsden Hospital

London, Other, SW3 6JJ, United Kingdom

Location

Sarah Cannon Research Institute UK

London, Other, W1G 6AD, United Kingdom

Location

UCL Cancer Institute

London, Other, WC1E6DD, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, Other, M20 4BX, United Kingdom

Location

The Royal Marsden Hospital (Surrey)

Sutton, Other, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck; Esophageal Squamous Cell Carcinoma; Prostatic Neoplasms; Melanoma

Interventions

SGN-LIV1A; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: July 23, 2019
• First Posted: July 25, 2019
• Study Start: October 9, 2019
• Primary Completion: November 28, 2023
• Study Completion: November 28, 2023
• Last Updated: March 10, 2025
• Results First Posted: March 10, 2025

Record last verified: 2025-02

Locations

GB (6); US (27); IT (11); TW (4); AU (8); KR (10)