Safety and Efficacy of OBX-115 in Advanced/Metastatic Melanoma Resistant to Immune Checkpoint Inhibitors

Study Overview
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Brief Summary
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This is a study to investigate the safety and efficacy of an investigational regimen, OBX-115, in adult participants with advanced/metastatic melanoma.

Detailed Description
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Primary Objective (Phase 1): • Assess the safety and tolerability of OBX-115 regimen Primary Objective (Phase 2): • Evaluate preliminary efficacy of OBX-115 regimen in melanoma as measured by the investigator using objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Secondary (Phase 1): • Assess preliminary efficacy of OBX-115 regimen by evaluating ORR Secondary (Phase 2): • Evaluate safety and tolerability of OBX 115 based on the collected AE data Secondary (both Phase 1 and Phase 2): Evaluate duration of response (DOR): To evaluate the duration from the time that criteria are met for CR or PR per RECIST v1.1 as assessed by the investigator until disease progression or death due to melanoma. Evaluate disease control rate (DCR): To evaluate the percentage of participants with a best overall confirmed response of CR or PR at any time plus stable disease (SD) for at least 4 weeks per RECIST v1.1 as assessed by the investigator. Evaluate progression-free survival (PFS): To evaluate the time from the date of OBX-115 infusion until disease progression per RECIST v1.1 as assessed by the investigator or death due to any cause. Evaluate overall survival (OS): To evaluate the time from the date of OBX-115 infusion to death due to any cause Evaluate feasibility of the manufacturing process: Evaluated as the proportion of OBX-115 products initiated for manufacturing that pass release criteria for infusion.

Official Title
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A Phase 1/2, Open-Label Study to Investigate the Safety and Efficacy of Membrane Bound IL15 Expressing Tumor-Infiltrating Lymphocytes (OBX-115) In Participants With Unresectable or Metastatic Melanoma Resistant to Checkpoint Inhibitors and After BRAF-MEK Targeting Therapy in Participants With BRAF Mutated Melanoma

Conditions
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Tumor Skin, Metastatic Melanoma, Melanoma

Intervention / Treatment
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* Biological: OBX-115


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be 18 years of age or older at the time of signing the informed consent. Participant has a histologically confirmed diagnosis of advanced/metastatic melanoma. Participant experienced documented radiographic disease progression after systemic therapy containing a programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) blocking antibody. If the tumor is BRAF V600 mutation-positive, the participant should also have received a BRAF inhibitor with or without a MEK inhibitor. Participant is assessed as having at least one resectable lesion for OBX-115 generation. After tumor tissue procurement, the participant will have at least one remaining measurable lesion, as defined by RECIST v1.1. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and an estimated life expectancy of >6 months. Participant has recovered from all prior anticancer treatment-related AEs to at least Grade 1 (per Common Terminology Criteria for Adverse Events [CTCAE]). Participants must have completed post-operative recovery from any prior surgical procedures with wound healing and resolution of all surgical complications prior to planned tumor procurement surgery. Both male and female (women of childbearing potential) participants agree to the follow protocol specified contraceptive and/or abstinence requirements. Participant has protocol specified hematologic parameters for absolute neutrophil count (ANC) and platelet count. Participant has adequate cardiac, liver and kidney organ function as specified in the protocol. Pulmonary function test may be required. Exclusion Criteria: Participant has melanoma of uveal/ocular origin. Participant has a history of brain metastases or leptomeningeal disease. Participant has an active medical illness(es) that, in the opinion of the Investigator, would pose increased risks for study participation. Participant has any form of primary or acquired immunodeficiency. Participant has a history of hypersensitivity to any component of the study intervention. Participant had another primary malignancy within the previous 3 years (with protocol specified exceptions). Participant has a history of allogeneic organ transplant, allogeneic cell therapy, or genetically engineered cell therapy. Prior non-engineered TIL therapy is allowed. Participant requires systemic steroid therapy >10 mg/day of prednisone or equivalent. Participant received a live or attenuated vaccination within 28 days prior to the start of lymphodepletion (LD). Participant has evidence of positive infectious disease screening infections requiring ongoing systemic treatment or identified during screening.

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
Interventional Model Description: Single group assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants with advanced/metastatic melanoma<br>Participants will receive conditioning therapy prior to administration on OBX-115 regimen. | Biological: OBX-115<br>* A tumor sample is obtained from each participant for autologous OBX-115 manufacture. After lymphodepletion including cyclophosphamide and fludarabine, participant will receive OBX-115 infusion, followed by a short course of acetazolamide.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and nature of dose-limiting toxicities (DLTs) | • Incidence of dose-limiting toxicities (DLTs) during the first 28 days after OBX-115 administration. | 28 Days | 
| The proportion of participants who have a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 | • The proportion of participants who have a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 as assessed by the Investigator from the date of OBX-115 infusion until disease progression, death, start of a new anticancer therapy, withdrawal of consent, or end of study, whichever comes first | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of participants who have a confirmed CR or PR per RECIST v1.1 | • The proportion of participants who have a confirmed CR or PR per RECIST v1.1 as assessed by the Investigator from the date of OBX-115 infusion until disease progression, death, start of a new anticancer therapy, withdrawal of consent, or end of study, whichever comes first | 2 years | 
| Incidence of AEs | • Incidence of treatment-emergent adverse events (TEAEs), including SAEs, study intervention related AEs, and AEs leading to early discontinuation of study intervention or withdrawal from the Assessment Period or death up to 2 years after initiation of study intervention | 2 years |