Safety and Efficacy of OBX-115 in Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT06060613
• Recruitment Status: Recruiting
• First Posted: September 29, 2023
• Last Update Posted: April 11, 2024
• Sponsor: Obsidian Therapeutics, Inc.
• Information provided by (Responsible Party): Obsidian Therapeutics, Inc.

Tracking Information

• First Submitted Date: September 22, 2023
• First Posted Date: September 29, 2023
• Last Update Posted Date: April 11, 2024
• Actual Study Start Date: October 25, 2023
• Estimated Primary Completion Date: October 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 30, 2024)

• Incidence and nature of dose-limiting toxicities (DLTs) [ Time Frame: 28 Days ]
  • Incidence of dose-limiting toxicities (DLTs) during the first 28 days after OBX-115 infusion (Phase 1).
• The proportion of participants who have a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 [ Time Frame: 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 (Phase 2)

Original Primary Outcome Measures (submitted: September 28, 2023)

• Incidence and nature of dose-limiting toxicities (DLTs) [ Time Frame: 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 [ Time Frame: 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

Current Secondary Outcome Measures (submitted: January 30, 2024)

• The proportion of participants who have a confirmed CR or PR per RECIST v1.1 [ Time Frame: 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 (Phase 1)
• Incidence of AEs [ Time Frame: 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

Original Secondary Outcome Measures (submitted: September 28, 2023)

• The proportion of participants who have a confirmed CR or PR per RECIST v1.1 [ Time Frame: 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 [ Time Frame: 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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of OBX-115 in Advanced Solid Tumors
• Official Title: 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 Advanced Solid Tumors
• Brief Summary: This is a study to investigate the safety and efficacy of an investigational OBX-115 regimen in adult participants with advanced solid tumors.

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 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 cancer.
• 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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Single group assignment

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Tumor Skin
• Metastatic Melanoma
• Melanoma
• Lung Cancer
• Metastatic Lung Cancer
• Non Small Cell Lung Cancer
• Metastatic Non Small Cell Lung Cancer

Intervention

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.

Study Arms

Experimental: Participants with advanced solid tumors

Participants will receive conditioning therapy prior to administration of OBX-115 regimen.

Intervention: Biological: OBX-115

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 30, 2024): 52
• Original Estimated Enrollment (submitted: September 28, 2023): 32
• Estimated Study Completion Date: October 30, 2027
• Estimated Primary Completion Date: October 30, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Participant must be 18 years of age or older at the time of signing the informed consent.
2. Participant has a histologically confirmed diagnosis of advanced/metastatic melanoma ore relapsed refractory metastatic non-small cell lung cancer (NSCLC).
3. 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. Participants with non-small cell lung cancer should have relapsed or are refractory to approved systemic therapies (approved ICI-based regimen for all appropriate participants and/or an approved targeted therapy for known molecular abnormalities if applicable to their disease).
4. Participant is assessed as having at least one lesion (or aggregate lesions) suitable for OBX-115 generation.
5. After tumor tissue procurement, the participant will have at least one remaining measurable lesion, as defined by RECIST v1.1.
6. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and an estimated life expectancy of >6 months.
7. Participant has recovered from all prior anticancer treatment-related AEs to at least Grade 1 (per Common Terminology Criteria for Adverse Events [CTCAE]).
8. 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.
9. Both male and female (women of childbearing potential) participants agree to the follow protocol specified contraceptive and/or abstinence requirements.
10. Participant has protocol specified hematologic parameters for absolute neutrophil count (ANC) and platelet count.
11. Participant has adequate cardiac, liver, lung, and kidney organ function as specified in the protocol.

Exclusion Criteria:

1. Participant has melanoma of uveal origin.
2. Participant has a history of brain metastases or leptomeningeal disease.
3. Participant has an active medical illness(es) that, in the opinion of the Investigator, would pose increased risks for study participation.
4. Participants with non-small cell lung cancer with refractory and clinically significant pleural effusions.
5. Participant has any form of primary or acquired immunodeficiency.
6. Participant has a history of hypersensitivity to any component of the study intervention.
7. Participant had another primary malignancy within the previous 3 years (with protocol specified exceptions).
8. Participant has a history of allogeneic organ transplant, allogeneic cell therapy, or genetically engineered cell therapy. Prior unegineered TIL cell therapy is allowed.
9. Participant requires systemic steroid therapy >10 mg/day of prednisone or equivalent.
10. Participant received a live or attenuated vaccination within 28 days prior to the start of lymphodepletion (LD).
11. Participant has evidence of positive infectious disease screening and/or any active uncontrolled viral, bacterial, or fungal disease requiring ongoing systemic treatment or identified during screening.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Obsidian Therapeutics; 781-202-5423; OBX115-2301TRIAL@OBSIDIANTX.COM

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT06060613
• Other Study ID Numbers: OBX115-23-01
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Obsidian Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Obsidian Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Obsidian Therapeutics, Inc.
• Verification Date: April 2024