Brentuximab Vedotin With Pembrolizumab in Metastatic Solid Tumors

Study Overview
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Brief Summary
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This trial will find out whether brentuximab vedotin and pembrolizumab work together to treat different types of cancer. There will be several different types of cancer studied in the trial. The cancer must have spread to other parts of the body (metastatic). The study will also find out what side effects occur. A side effect is anything the treatment does besides treat cancer. This is a multi-cohort study.

Official Title
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A Phase 2 Study of Brentuximab Vedotin in Combination With Pembrolizumab in Subjects With Metastatic Solid Malignancies After Progression on Prior PD-1 Inhibitor Treatment

Conditions
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Melanoma, Non-small Cell Lung Cancer, Squamous Cell Carcinoma of the Head and Neck

Intervention / Treatment
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* Drug: brentuximab vedotin
* Drug: pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Participants must have Metastatic squamous or nonsquamous non-small cell lung cancer (NSCLC) (without known targetable EGFR, ALK, ROS1, or BRAF mutations) who either a) have not yet received frontline therapy for metastatic disease and without prior exposure to anti PD-1/PD-L1 or b) are relapsed/refractory with progression on anti PD-1/PD therapy. Relapsed/refractory metastatic cutaneous melanoma (regardless of mutation status) with progression on a PD-1 inhibitor Metastatic head and neck squamous cell carcinoma (HNSCC) who have not yet received frontline therapy for metastatic disease and without prior exposure to a PD-1/PD-L1 inhibitor. Cohorts 1-4 only: Melanoma participants must be currently on PD-1 checkpoint inhibitor (CPI) therapy (e.g. nivolumab or pembrolizumab) or had their last dose of PD-1 CPI containing therapy as the last previous line of therapy within 90 days prior to enrollment; PD-1 CPI therapy must be the immediate prior line of treatment. Cohorts 1-4 only: Participants must have progressed on treatment with an anti-PD-1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other CPIs or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria. Have received at least 2 doses of an approved PD-1 inhibitor. Have demonstrated disease progression (PD) after a PD-1 inhibitor as defined by RECIST v1.1. Progressive disease has been documented within 90 days from the last dose of PD-1 inhibitor. Participants with melanoma will need iRECIST confirmation of progression with a second assessment at least four weeks after the initial date of progressive disease NSCLC participants on PD-1 inhibitor containing therapy for less than 90 days will need iRECIST confirmation of progression at least 4 weeks after the initial date of progressive disease Tumor tissue sample obtained within 3 months prior to enrollment is required, and no systemic anticancer therapy given after the sample was obtained. An Eastern Cooperative Oncology Group (ECOG) Performance Status score of equal or less than 1 Exclusion Criteria Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Prior immunosuppressive chemotherapy, any immunotherapy other than a PD-1 inhibitor within 4 weeks of first study drug dose. History of another malignancy within 3 years before the first dose of study drug or any evidence of residual disease from a previously diagnosed malignancy.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination Therapy<br>brentuximab vedotin + pembrolizumab | Drug: brentuximab vedotin<br>* 1.8 mg/kg given into the vein (IV; intravenously) every 3 weeks<br>* Other names: ADCETRIS;Drug: pembrolizumab<br>* 200 mg given intravenously every 3 weeks<br>* Other names: KEYTRUDA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed objective response rate (ORR) based on investigator assessment using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) criteria | Confirmed ORR per RECIST v1.1 is defined as the proportion of participants whose best overall response is a confirmed complete response (CR) or partial response (PR) per RECIST v1.1. | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response (DOR) based on investigator assessment using RECIST v1.1 criteria | DOR per RECIST v1.1 is defined as the time from start of the first documentation of confirmed objective tumor response (CR or PR) per RECIST v1.1 to the first documentation of PD (per RECIST v1.1) or to death due to any cause, whichever comes first. | Up to approximately 3 years | 
| Progression-free survival (PFS) based on investigator assessment using RECIST v1.1 criteria | PFS is defined as the time from start of study treatment to first documentation of objective tumor progression (PD per RECIST v1.1), or to death due to any cause, whichever comes first. | Up to approximately 3 years | 
| ORR per iRECIST by investigator assessment | ORR per iRECIST is defined as the proportion of participants with confirmed CR or PR based on iRECIST guidelines | Up to approximately 2 years | 
| iDOR per iRECIST by investigator assessment | DOR per iRECIST is defined as the time from first documentation of confirmed objective response (CR or PR) based on iRECIST guidelines by investigator assessment to the first documentation of confirmed objective tumor progression per iRECIST by investigator assessment, or to death due to any cause, whichever comes first. | Up to approximately 3 years | 
| iPFS per iRECIST by investigator assessment | iPFS is defined as the time from start of study treatment to the first documentation of confirmed objective tumor progression per iRECIST by investigator assessment, treatment discontinuation following the unconfirmed progression or death due to any cause, whichever comes first. | Up to approximately 3 years | 
| Incidence of adverse events (AEs) | National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Analyses of AEs will be summarized with descriptive statistics. | Up to approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Seattle Genetics