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

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

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.

Study Overview

• Status: Completed
• Conditions: Melanoma; Carcinoma, Non-Small- Cell Lung
• Intervention / Treatment: Drug: SEA-CD40; Drug: pemetrexed; Drug: carboplatin; Drug: pembrolizumab (KEYTRUDA®)

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1R 2J6
    • CHU de Quebec-Université Laval
• France
  • Other
    • Suresnes, Other, France, 92150
      • Hopital Foch
• Germany
  • Other
    • Heidelberg, Other, Germany, 69120
      • Universitatsklinikum Heidelberg
• Spain
  • Other
    • Madrid, Other, Spain, 28050
      • START Madrid-CIOCC_Hospital HM Sanchinarro
    • Valencia, Other, Spain, 46010
      • Hospital Clinico Universitario de Valencia
• Sweden
  • Other
    • Stockholm, Other, Sweden, 171 76
      • Karolinska University Hospital
• United States
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology Group
  • California
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute
    • San Francisco, California, United States, 94134
      • University of California at San Francisco
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center Research Institute/Sutter Medical Centre
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists - South Region
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists - North Region
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer & Blood Center, LLC
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Community Health Network
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • American Oncology Networks LLC
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Allina Health Cancer Institute
    • Saint Paul, Minnesota, United States, 55101
      • Regions Cancer Care Center
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center/ Carol G. Simon Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center Research, LLC
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic - Taussig Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente Oregon
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology-Nashville/Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern/Simmons Cancer Center
    • Houston, Texas, United States, 77030-4095
      • MD Anderson Cancer Center / University of Texas
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Carbone Cancer Center / University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Melanoma Arm; SEA-CD40 + pembrolizumab	Drug: SEA-CD40; Given into the vein (IV; intravenously); schedule is cohort-specific; Drug: pembrolizumab (KEYTRUDA®); Given by IV; schedule is cohort-specific.
Experimental: NSCLC Arm; SEA-CD40 + pembrolizumab + pemetrexed + carboplatin	Drug: SEA-CD40; Given into the vein (IV; intravenously); schedule is cohort-specific; Drug: pemetrexed; Given by IV on Day 1 of each 21-day cycle.; Other Names: Alimta; Drug: carboplatin; Given by IV on Day 1 of Cycles 1-4. Each cycle will be 21 days long.; Other Names: Paraplatin; Drug: pembrolizumab (KEYTRUDA®); Given by IV; schedule is cohort-specific.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Objective Response Rate (cORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Per Investigator Assessment	cORR is defined as the percentage of participants achieving a confirmed complete response (CR) or partial response (PR) according to RECIST v1.1. CR: disappearance of all target, non-target lesions, all lymph nodes must be non-pathological in size (<10 millimeter [mm] short axis), PR: at least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters persistence of one or more non-target lesions.	From start of study treatment until CR or PR (maximum up to 15.2 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Related TEAEs, Greater Than or Equal to (>=) Grade 3 TEAEs, Treatment Emergent Serious Adverse Event (TESAE), Treatment Related TESAE	Adverse event (AE):untoward medical occurrence in participant/clinical investigational participant administered medicinal product which doesn't necessarily have causal relationship with treatment. Serious AE (SAE):any AE that at any dose resulted in death, life threatening, required hospitalization/prolongation of hospitalization, disabling/incapacitating, congenital anomaly/birth defects.AEs included SAEs,non-SAEs.TEAEs:newly occurring/worsening after 1st dose of treatment.Treatment related TEAEs:related to treatment;relatedness judged by investigator. TEAEs graded according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) v4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threating, grade 5=fatal). TESAEs:any TEAE that at any dose suspected to cause death, life-threatening, required hospitalization, disabling/incapacitating, congenital anomaly/birth defect. Treatment related TESAEs:related to treatment; relatedness judged by investigator.	From first dose of the study treatment (Day 1) up to approximately 18.5 months
Number of Participants With Grade Shift From Baseline to Maximum Post-Baseline in Serum Chemistry Laboratory Abnormalities Assessed by NCI CTCAE	In this outcome measure, number of participants with baseline laboratory chemistry values as per NCI-CTCAE grade (grade 0=within normal limits, grade 1=mild, grade 2=moderate, grade 3=severe, grade 4= life-threatening) and corresponding changes or shift to the worst CTC grades post baseline were presented. Laboratory parameters evaluated: alanine aminotransferase increased, albumin decreased, alkaline phosphatase increased, aspartate aminotransferase increased, calcium corrected for albumin, creatinine increased, glomerular filtration rate (GFR) estimated decreased, glucose decreased, lactate dehydrogenase increased, potassium, sodium, total bilirubin increased. Baseline was defined as last non-missing grade before first dose of study treatment and worst post-baseline value defined as worst value post study treatment. Only those categories in which at least 1 participant had data in any reporting group were reported.	Baseline up to approximately 15.8 months
Number of Participants With Grade Shift From Baseline to Maximum Post-Baseline in Hematology Parameters Assessed by NCI CTCAE	In this outcome measure, number of participants with baseline laboratory hematology values as per NCI-CTCAE grade (grade 0= within normal limits, grade 1=mild, grade 2=moderate, grade 3= severe, grade 4= life-threatening) and corresponding changes or shift to the worst CTC grades post baseline were presented. Laboratory parameters evaluated: hemoglobin- decreased and increased, leukocytes- decreased and increased, lymphocytes- decreased and increased, neutrophils decreased, platelets decreased. Baseline was defined as last non-missing grade before first dose of study treatment and worst post-baseline value defined as worst value post study treatment. Only those categories in which at least 1 participant had data in any reporting group were reported.	Baseline up to approximately 15.8 months
Number of Participants With Treatment Interruptions, Dose Reductions, Treatment Discontinuations Due to Adverse Events	An AE is defined as any untoward medical occurrence in participant/clinical investigational participant administered medicinal product which doesn't necessarily have causal relationship with treatment. Number of participants with dose interruption (SEA-CD40 treatment being temporarily stopped), dose reduction (SEA-CD40 decrease in dose) and dose discontinuation (SEA-CD40 treatment permanently stopped) due to adverse events were reported in this outcome measure.	From first dose of the study treatment (Day 1) up to approximately 18.5 months
Disease Control Rate (DCR) Per Investigator Assessment	DCR is defined as the percentage of participants who achieved a confirmed CR or PR according to RECIST v1.1 as assessed by the investigator or met the stable disease (SD) criteria at least once after start of study treatment at a minimum interval of 5 weeks. CR: disappearance of all target, non-target lesions, all lymph nodes must be non-pathological in size (<10 mm short axis), PR: at least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters persistence of one or more non-target lesions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase in lesions to qualify for progressive disease (PD) referring smallest sum diameter, PD: at least 20% increase (including absolute increase of at least 5 mm) in sum of diameters of target lesions, taking reference smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.	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 15.2 months)
Duration of Response (DOR) Per Investigator Assessment	DOR: time from first documentation of OR (confirmed CR or PR) to first documentation of PD or death due to any cause, whichever occurred first. Per RECIST v1.1- CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR: >=30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. Participants with no PD and were still on study at time of analysis or were removed from study prior to documentation of PD were censored at last disease assessment documenting absence of PD. Participants who started new anticancer treatment prior to documentation of PD were censored at last disease assessment prior to start of new treatment. PD: at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study. In addition to relative increase of 20%, sum must demonstrate absolute increase of 0.5 cm. Appearance of 1 or more new lesions. Kaplan-Meier method was used.	From the first documentation of CR or PR to PD or death due to any cause or censoring, whichever occurred first (maximum up to 11.1 months)
Progression Free Survival (PFS) Per Investigator Assessment	PFS is defined as time from start of study treatment to first documentation of PD by RECIST v1.1 or death due to any cause, whichever occurred first. Participants with no PD and were still on study at time of analysis or who were removed from study prior to documentation of PD were censored at the date of last disease assessment documenting absence of PD. Participants who started new anticancer treatment prior to documentation of PD were censored at date of last disease assessment prior to start of new treatment. PD: At least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (this included baseline sum if that is the smallest on study). In addition to relative increase of 20%, the sum must also demonstrate an absolute increase of at least 0.5 cm. Appearance of one or more new lesions was also considered progression. Kaplan-Meier method was used.	From first dose of study treatment to the date of PD or death due to any cause or censoring, whichever occurred first (maximum up to 13.9 months)
Overall Survival (OS)	OS is defined as the time from the start of study treatment to date of death due to any cause. In the absence of death, survival time was censored at the last date the participant was known to be alive. Kaplan-Meier method was used for analysis.	From start of study treatment to death due to any cause or censoring date (maximum up to 23.6 months)

Collaborators and Investigators

• Sponsor: Seagen Inc.
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Jonathan Hayman, MD, Seagen Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2021
• Primary Completion (Actual): January 3, 2024
• Study Completion (Actual): November 25, 2024

Study Registration Dates

• First Submitted: July 30, 2021
• First Submitted That Met QC Criteria: July 30, 2021
• First Posted (Actual): August 6, 2021

Study Record Updates

• Last Update Posted (Actual): May 11, 2025
• Last Update Submitted That Met QC Criteria: April 23, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: NSCLC; Non-small cell lung cancer; Seattle Genetics; Relapsed melanoma; Refractory melanoma; Metastatic uveal melanoma; Metastatic PD-(L)1-naïve melanoma; Non-squamous NSCLC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Carcinoma, Non-Small-Cell Lung; Melanoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Pemetrexed; Carboplatin; Pembrolizumab
• Other Study ID Numbers: SGNS40-002; KEYNOTE-C86 (Other Identifier: Merck Sharp & Dohme Corp)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No