A Study of SEA-CD40 Given With Other Drugs in Cancers

NCT ID: NCT04993677

Last Updated: 2025-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 77 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-06
• Study Completion Date: 2024-11-25

Brief Summary

This trial is being done to see if an experimental drug (SEA-CD40) works when it's given with other cancer drugs to treat some types of cancer. It will also study side effects from the drug.

There are 2 parts in this trial. In one part, participants have melanoma that has come back after treatment or can't be removed by surgery. Participants in this part will get SEA-CD40 and pembrolizumab. In the other part, participants have non-small cell lung cancer (NSCLC) that has spread through their body. These participants will get SEA-CD40, pembrolizumab, carboplatin, and pemetrexed.

Conditions

Melanoma; Carcinoma, Non-Small- Cell Lung

Study Design

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

Study Groups

Melanoma Arm

SEA-CD40 + pembrolizumab

Group Type: EXPERIMENTAL

SEA-CD40

Intervention Type: DRUG

Given into the vein (IV; intravenously); schedule is cohort-specific

pembrolizumab (KEYTRUDA®)

Intervention Type: DRUG

Given by IV; schedule is cohort-specific.

NSCLC Arm

SEA-CD40 + pembrolizumab + pemetrexed + carboplatin

Group Type: EXPERIMENTAL

SEA-CD40

Intervention Type: DRUG

Given into the vein (IV; intravenously); schedule is cohort-specific

pembrolizumab (KEYTRUDA®)

Intervention Type: DRUG

Given by IV; schedule is cohort-specific.

pemetrexed

Intervention Type: DRUG

Given by IV on Day 1 of each 21-day cycle.

carboplatin

Intervention Type: DRUG

Given by IV on Day 1 of Cycles 1-4. Each cycle will be 21 days long.

Interventions

SEA-CD40

Given into the vein (IV; intravenously); schedule is cohort-specific

Intervention Type: DRUG

pembrolizumab (KEYTRUDA®)

Given by IV; schedule is cohort-specific.

Intervention Type: DRUG

pemetrexed

Given by IV on Day 1 of each 21-day cycle.

Intervention Type: DRUG

carboplatin

Given by IV on Day 1 of Cycles 1-4. Each cycle will be 21 days long.

Intervention Type: DRUG

Other Intervention Names

Alimta; Paraplatin

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed unresectable malignancy defined as one of the following:

• Cohort 1: Relapsed and/or refractory metastatic melanoma

• Uveal/ocular melanoma is excluded
• Must have progressed on treatment with an anti-PD-(L)1 mAb. PD-(L)1 treatment progression is defined as meeting all of the following criteria:

• Has received at least 2 doses of an approved anti-PD-(L)1 mAb
• Has demonstrated disease progression after PD-(L)1 as defined by RECIST v1.1.
• Progressive disease has been documented within 12 weeks from the last dose of anti- PD-(L)1 mAb
• Last dose of anti-PD-(L)1 must have been within 90 days prior to enrollment
• Participants with a targetable BRAF mutation must have been treated with, been intolerant of, or declined treatment with BRAF/MEK targeted therapy prior to study entry
• Cohort 2: Metastatic uveal melanoma

• Must not have received prior treatment for advanced or metastatic disease except for prior adjuvant/neoadjuvant immunotherapy
• No prior liver-directed therapy
• Cohort 3: Metastatic PD-(L)1-naive melanoma

• Uveal/ocular melanoma is excluded
• Must not have received prior treatment for advanced or metastatic disease except for prior adjuvant/neoadjuvant immunotherapy.
• For participants with a targetable BRAF mutation, prior BRAF/MEK targeted therapy is allowed if completed 4 weeks prior to first dose of study treatment.
• Cohorts 4 and 5: Non-squamous NSCLC

• Participants must have stage IV disease per AJCC 8th edition
• No known driver mutations/alterations mutation for which targeted therapy is available
• Must have non-squamous histology.
• No prior therapy for metastatic disease
• No prior treatment with anti-PD-(L)1 or PD-L2 agent or an antibody targeting other immuno-regulatory receptors or mechanisms
• Able to provide archival tumor tissue from locations not radiated prior to biopsy. If archival tumor sample is not available a fresh baseline biopsy is required.
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
• Measurable disease per RECIST v1.1 at baseline

Exclusion Criteria

• History of another malignancy within 3 years of first dose of study drug
• Active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Previous exposure to CD40-targeted therapy
• Currently on chronic systemic steroids in excess of physiologic replacement
• Has had an allogeneic tissue/solid organ transplant.
• History of autoimmune disease that has required systemic treatment in the past 2 years

• 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

Jonathan Hayman, MD

Role: STUDY_DIRECTOR

Seagen Inc.

Locations

Highlands Oncology Group

Springdale, Arkansas, United States

The Angeles Clinic and Research Institute

Los Angeles, California, United States

California Pacific Medical Center Research Institute/Sutter Medical Centre

San Francisco, California, United States

University of California at San Francisco

San Francisco, California, United States

Florida Cancer Specialists - South Region

Fort Myers, Florida, United States

Florida Cancer Specialists - North Region

St. Petersburg, Florida, United States

University Cancer & Blood Center, LLC

Athens, Georgia, United States

Rush University Medical Center

Chicago, Illinois, United States

Community Health Network

Indianapolis, Indiana, United States

American Oncology Networks LLC

Baton Rouge, Louisiana, United States

Allina Health Cancer Institute

Minneapolis, Minnesota, United States

University of Minnesota

Minneapolis, Minnesota, United States

Regions Cancer Care Center

Saint Paul, Minnesota, United States

Morristown Medical Center/ Carol G. Simon Cancer Center

Morristown, New Jersey, United States

Duke University Medical Center

Durham, North Carolina, United States

Gabrail Cancer Center Research, LLC

Canton, Ohio, United States

Cleveland Clinic - Taussig Cancer Institute

Cleveland, Ohio, United States

Kaiser Permanente Oregon

Portland, Oregon, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Tennessee Oncology-Nashville/Sarah Cannon Research Institute

Nashville, Tennessee, United States

University of Texas Southwestern/Simmons Cancer Center

Dallas, Texas, United States

MD Anderson Cancer Center / University of Texas

Houston, Texas, United States

Carbone Cancer Center / University of Wisconsin

Madison, Wisconsin, United States

CHU de Quebec-Universite Laval

Québec, , Canada

Hopital Foch

Suresnes, Other, France

Universitatsklinikum Heidelberg

Heidelberg, Other, Germany

START Madrid-CIOCC_Hospital HM Sanchinarro

Madrid, Other, Spain

Hospital Clinico Universitario de Valencia

Valencia, Other, Spain

Karolinska University Hospital

Stockholm, Other, Sweden

Countries

United States; Canada; France; Germany; Spain; Sweden

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

KEYNOTE-C86

Identifier Type: OTHER

Identifier Source: secondary_id

SGNS40-002

Identifier Type: -

Identifier Source: org_study_id