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

Study Overview
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Brief Summary
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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.

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

Conditions
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Melanoma, Carcinoma, Non-Small- Cell Lung

Intervention / Treatment
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* Drug: SEA-CD40
* Drug: pembrolizumab
* Drug: pemetrexed
* Drug: carboplatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Incidence of laboratory abnormalities | To be summarized using descriptive statistics | From start of treatment to 30-37 days after last dose, approximately 2 years | 
| Incidence of dose alterations | To be summarized using descriptive statistics | Duration of treatment, approximately 2 years | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-small cell lung cancer, Seattle Genetics, Relapsed melanoma, Refractory melanoma, Metastatic uveal melanoma, Metastatic PD-(L)1-naïve melanoma, Non-squamous NSCLC, NSCLC