Clinical trial NCT04993677: A Study of SEA-CD40 Given With Other Drugs in Cancers
Official title: An Open-label, Phase 2 Basket Study of SEA-CD40 Combination Therapies in Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma
Carcinoma, Non-Small- Cell Lung
Keywords: Relapsed melanoma
Refractory melanoma
Metastatic uveal melanoma
Metastatic PD-(L)1-naïve melanoma
Non-squamous NSCLC
NSCLC
Non-small cell lung cancer
Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2021-08-06
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Confirmed Objective Response Rate (cORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Per Investigator Assessment
timeFrame: From start of study treatment until CR or PR (maximum up to 15.2 months)
Secondary outcomes:
measure: 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
timeFrame: From first dose of the study treatment (Day 1) up to approximately 18.5 months
measure: Number of Participants With Grade Shift From Baseline to Maximum Post-Baseline in Serum Chemistry Laboratory Abnormalities Assessed by NCI CTCAE
timeFrame: Baseline up to approximately 15.8 months
measure: Number of Participants With Grade Shift From Baseline to Maximum Post-Baseline in Hematology Parameters Assessed by NCI CTCAE
timeFrame: Baseline up to approximately 15.8 months
measure: Number of Participants With Treatment Interruptions, Dose Reductions, Treatment Discontinuations Due to Adverse Events
timeFrame: From first dose of the study treatment (Day 1) up to approximately 18.5 months
measure: Disease Control Rate (DCR) Per Investigator Assessment
timeFrame: 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)
measure: Duration of Response (DOR) Per Investigator Assessment
timeFrame: 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)
measure: Progression Free Survival (PFS) Per Investigator Assessment
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: From start of study treatment to death due to any cause or censoring date (maximum up to 23.6 months)
Other outcomes:
Locations:
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center Research Institute/Sutter Medical Centre
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - South Region
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists - North Region
state: Florida
city: Athens
country: United States
facility: University Cancer & Blood Center, LLC
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Community Health Network
state: Indiana
city: Baton Rouge
country: United States
facility: American Oncology Networks LLC
state: Louisiana
city: Minneapolis
country: United States
facility: Allina Health Cancer Institute
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Cancer Care Center
state: Minnesota
city: Morristown
country: United States
facility: Morristown Medical Center/ Carol G. Simon Cancer Center
state: New Jersey
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center Research, LLC
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic - Taussig Cancer Institute
state: Ohio
city: Portland
country: United States
facility: Kaiser Permanente Oregon
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology-Nashville/Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern/Simmons Cancer Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center / University of Texas
state: Texas
city: Madison
country: United States
facility: Carbone Cancer Center / University of Wisconsin
state: Wisconsin
city: Quebec
country: Canada
facility: CHU de Quebec-Universite Laval
city: Suresnes
country: France
facility: Hopital Foch
state: Other
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg
state: Other
city: Madrid
country: Spain
facility: START Madrid-CIOCC_Hospital HM Sanchinarro
state: Other
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
state: Other
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
state: Other
Study officials:
affiliation: Seagen Inc.
name: Jonathan Hayman, MD
role: STUDY_DIRECTOR
References: