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

Melanoma Clinical Trial

Official title:

An Open-label, Phase 2 Basket Study of SEA-CD40 Combination Therapies in Advanced Malignancies

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04993677
• Other study ID #: SGNS40-002
• Secondary ID: KEYNOTE-C86
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 6, 2021
• Est. completion date: October 31, 2025

Study information

• Verified date: February 2024
• Source: Seagen Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 77
• Est. completion date: October 31, 2025
• Est. primary completion date: January 3, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Melanoma

Intervention

Drug:
• SEA-CD40
Given into the vein (IV; intravenously); schedule is cohort-specific
• pembrolizumab
Given by IV; schedule is cohort-specific.
• pemetrexed
Given by IV on Day 1 of each 21-day cycle.
• carboplatin
Given by IV on Day 1 of Cycles 1-4. Each cycle will be 21 days long.

Locations

Country	Name	City	State
Canada	CHU de Quebec-Universite Laval	Quebec
France	Hopital Foch	Suresnes	Other
Germany	Universitatsklinikum Heidelberg	Heidelberg	Other
Spain	START Madrid-CIOCC_Hospital HM Sanchinarro	Madrid	Other
Spain	Hospital Clinico Universitario de Valencia	Valencia	Other
Sweden	Karolinska University Hospital	Stockholm	Other
United States	University Cancer & Blood Center, LLC	Athens	Georgia
United States	American Oncology Networks LLC	Baton Rouge	Louisiana
United States	Gabrail Cancer Center Research, LLC	Canton	Ohio
United States	Rush University Medical Center	Chicago	Illinois
United States	Cleveland Clinic - Taussig Cancer Institute	Cleveland	Ohio
United States	University of Texas Southwestern/Simmons Cancer Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Florida Cancer Specialists - South Region	Fort Myers	Florida
United States	MD Anderson Cancer Center / University of Texas	Houston	Texas
United States	Community Health Network	Indianapolis	Indiana
United States	The Angeles Clinic and Research Institute	Los Angeles	California
United States	Carbone Cancer Center / University of Wisconsin	Madison	Wisconsin
United States	Allina Health Cancer Institute	Minneapolis	Minnesota
United States	University of Minnesota	Minneapolis	Minnesota
United States	Morristown Medical Center/ Carol G. Simon Cancer Center	Morristown	New Jersey
United States	Tennessee Oncology-Nashville/Sarah Cannon Research Institute	Nashville	Tennessee
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Kaiser Permanente Oregon	Portland	Oregon
United States	Regions Cancer Care Center	Saint Paul	Minnesota
United States	Florida Cancer Specialists - North Region	Saint Petersburg	Florida
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	Highlands Oncology Group	Springdale	Arkansas

Sponsors (2)

Lead Sponsor	Collaborator
Seagen Inc.	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirmed Objective Response Rate (ORR)	The proportion of participants who achieve a confirmed complete response (CR) or partial (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by the investigator.	Duration of treatment, approximately 2 years
Secondary	Incidence of adverse events (AEs)	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.	From start of treatment to 30-37 days after last dose, approximately 2 years
Secondary	Incidence of laboratory abnormalities	To be summarized using descriptive statistics	From start of treatment to 30-37 days after last dose, approximately 2 years
Secondary	Incidence of dose alterations	To be summarized using descriptive statistics	Duration of treatment, approximately 2 years
Secondary	Disease control rate (DCR) per investigator assessment	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.	From start of treatment until completion of response assessment, approximately 4 years
Secondary	Duration of response (DOR) per investigator assessment	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	From start of treatment until completion of response assessment, approximately 4 years
Secondary	Progression-free survival (PFS) per investigator assessment	The time from the start of study treatment to the first documentation of PD by RECIST v1.1 or death due to any cause	From start of treatment until completion of response assessment, approximately 4 years
Secondary	Overall survival (OS)	The time from the start of study treatment to date of death due to any cause	Duration of study, approximately 4 years