Safety and Efficacy of OBX-115 in Advanced/Metastatic Melanoma Resistant to Immune Checkpoint Inhibitors
Study Details
Study Description
Brief Summary
This is a study to investigate the safety and efficacy of an investigational regimen, OBX-115, in adult participants with advanced/metastatic melanoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
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):
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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.
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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.
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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.
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Evaluate overall survival (OS): To evaluate the time from the date of OBX-115 infusion to death due to any cause
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Evaluate feasibility of the manufacturing process: Evaluated as the proportion of OBX-115 products initiated for manufacturing that pass release criteria for infusion.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Participants with advanced/metastatic melanoma Participants will receive conditioning therapy prior to administration on OBX-115 regimen. |
Biological: OBX-115
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.
|
Outcome Measures
Primary Outcome Measures
- Incidence and nature of dose-limiting toxicities (DLTs) [28 Days]
• Incidence of dose-limiting toxicities (DLTs) during the first 28 days after OBX-115 administration.
- The proportion of participants who have a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 [2 years]
• 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
Secondary Outcome Measures
- The proportion of participants who have a confirmed CR or PR per RECIST v1.1 [2 years]
• 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
- Incidence of AEs [2 years]
• 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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Participant must be 18 years of age or older at the time of signing the informed consent.
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Participant has a histologically confirmed diagnosis of advanced/metastatic melanoma.
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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.
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Participant is assessed as having at least one resectable lesion for OBX-115 generation.
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After tumor tissue procurement, the participant will have at least one remaining measurable lesion, as defined by RECIST v1.1.
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Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and an estimated life expectancy of >6 months.
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Participant has recovered from all prior anticancer treatment-related AEs to at least Grade 1 (per Common Terminology Criteria for Adverse Events [CTCAE]).
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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.
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Both male and female (women of childbearing potential) participants agree to the follow protocol specified contraceptive and/or abstinence requirements.
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Participant has protocol specified hematologic parameters for absolute neutrophil count (ANC) and platelet count.
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Participant has adequate cardiac, liver and kidney organ function as specified in the protocol. Pulmonary function test may be required.
Exclusion Criteria:
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Participant has melanoma of uveal/ocular origin.
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Participant has a history of brain metastases or leptomeningeal disease.
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Participant has an active medical illness(es) that, in the opinion of the Investigator, would pose increased risks for study participation.
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Participant has any form of primary or acquired immunodeficiency.
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Participant has a history of hypersensitivity to any component of the study intervention.
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Participant had another primary malignancy within the previous 3 years (with protocol specified exceptions).
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Participant has a history of allogeneic organ transplant, allogeneic cell therapy, or genetically engineered cell therapy. Prior non-engineered TIL therapy is allowed.
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Participant requires systemic steroid therapy >10 mg/day of prednisone or equivalent.
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Participant received a live or attenuated vaccination within 28 days prior to the start of lymphodepletion (LD).
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Participant has evidence of positive infectious disease screening infections requiring ongoing systemic treatment or identified during screening.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Orlando Health Cancer Institute | Orlando | Florida | United States | 32806 |
| 2 | James Graham Brown Cancer Center | Louisville | Kentucky | United States | 40202 |
Sponsors and Collaborators
- Obsidian Therapeutics, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- OBX115-23-01