A Study of SEA-CD40 Given With Other Drugs in Cancers
- Conditions
- Carcinoma, Non-Small- Cell LungMelanoma
- Interventions
- Registration Number
- NCT04993677
- Lead Sponsor
- Seagen Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 77
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Histologically or cytologically confirmed unresectable malignancy defined as one of the following:
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Cohort 1: Relapsed and/or refractory metastatic melanoma
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Uveal/ocular melanoma is excluded
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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
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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
-
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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
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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.
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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
-
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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.
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Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
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Measurable disease per RECIST v1.1 at baseline
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description NSCLC Arm pembrolizumab (KEYTRUDA®) SEA-CD40 + pembrolizumab + pemetrexed + carboplatin Melanoma Arm SEA-CD40 SEA-CD40 + pembrolizumab Melanoma Arm pembrolizumab (KEYTRUDA®) SEA-CD40 + pembrolizumab NSCLC Arm SEA-CD40 SEA-CD40 + pembrolizumab + pemetrexed + carboplatin NSCLC Arm carboplatin SEA-CD40 + pembrolizumab + pemetrexed + carboplatin NSCLC Arm pemetrexed SEA-CD40 + pembrolizumab + pemetrexed + carboplatin
- Primary Outcome Measures
Name Time Method Confirmed Objective Response Rate (cORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Per Investigator Assessment From start of study treatment until CR or PR (maximum up to 15.2 months) 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.
- Secondary Outcome Measures
Name Time Method 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 From first dose of the study treatment (Day 1) up to approximately 18.5 months 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.
Number of Participants With Grade Shift From Baseline to Maximum Post-Baseline in Serum Chemistry Laboratory Abnormalities Assessed by NCI CTCAE Baseline up to approximately 15.8 months 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.
Number of Participants With Grade Shift From Baseline to Maximum Post-Baseline in Hematology Parameters Assessed by NCI CTCAE Baseline up to approximately 15.8 months 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.
Number of Participants With Treatment Interruptions, Dose Reductions, Treatment Discontinuations Due to Adverse Events From first dose of the study treatment (Day 1) up to approximately 18.5 months 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.
Disease Control Rate (DCR) Per Investigator Assessment 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) 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.
Duration of Response (DOR) Per Investigator Assessment 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) 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.
Progression Free Survival (PFS) Per Investigator Assessment 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) 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.
Overall Survival (OS) From start of study treatment to death due to any cause or censoring date (maximum up to 23.6 months) 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.
Trial Locations
- Locations (29)
Tennessee Oncology-Nashville/Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Allina Health Cancer Institute
🇺🇸Minneapolis, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, 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
Florida Cancer Specialists - North Region
🇺🇸Saint Petersburg, Florida, United States
University of California at San Francisco
🇺🇸San Francisco, California, United States
Florida Cancer Specialists - South Region
🇺🇸Fort Myers, Florida, United States
University Cancer & Blood Center, LLC
🇺🇸Athens, Georgia, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
American Oncology Networks LLC
🇺🇸Baton Rouge, Louisiana, United States
Community Health Network
🇺🇸Indianapolis, Indiana, United States
Regions Cancer Care Center
🇺🇸Saint Paul, Minnesota, United States
Morristown Medical Center/ Carol G. Simon Cancer Center
🇺🇸Morristown, New Jersey, 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
CHU de Quebec-Universite Laval
🇨🇦Quebec, Canada
University of Texas Southwestern/Simmons Cancer Center
🇺🇸Dallas, Texas, United States
Carbone Cancer Center / University of Wisconsin
🇺🇸Madison, Wisconsin, United States
MD Anderson Cancer Center / University of Texas
🇺🇸Houston, Texas, United States
Hopital Foch
🇫🇷Suresnes, Other, France
Universitatsklinikum Heidelberg
🇩🇪Heidelberg, Other, Germany
Karolinska University Hospital
🇸🇪Stockholm, Other, Sweden
START Madrid-CIOCC_Hospital HM Sanchinarro
🇪🇸Madrid, Other, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Other, Spain
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Highlands Oncology Group
🇺🇸Springdale, Arkansas, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States