Safety and Efficacy of OBX-115 in Advanced Solid Tumors (Agni-01)

April 27, 2026 updated by: Obsidian Therapeutics, Inc.

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

This is a study to investigate the safety and efficacy of an investigational OBX-115 regimen in adult participants with advanced solid tumors.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Blinded Independent Central Review (BICR) using objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Cohort 3)
  • 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 (Cohorts 1, 2, 4)

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 BICR until disease progression or death due to cancer (Phase 2 Cohort 3).
  • 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 (Phase 1 and Phase 2 Cohorts 1, 2, and 4).
  • 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 BICR (Phase 2 Cohort 3).
  • 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 (Phase 1 and Phase 2 Cohorts 1, 2, and 4).
  • 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 BICR or death due to any cause (Phase 2 Cohort 3).
  • 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 (Phase 1 and Phase 2 Cohorts 1, 2, and 4).
  • 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

Enrollment (Estimated)

208

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90025
        • Recruiting
        • The Angeles Clinic and Research Institute (Melanoma)
        • Principal Investigator:
          • Omid Hamid, MD
        • Contact:
      • Los Angeles, California, United States, 90033
        • Recruiting
        • USC Norris Comprehensive Cancer Center (Melanoma/NSCLC)
        • Principal Investigator:
          • Gino In, MD
        • Contact:
      • Stanford, California, United States, 94305
        • Recruiting
        • Stanford Cancer Institute (Melanoma/NSCLC)
        • Principal Investigator:
          • Allison Betof, MD
        • Contact:
    • Florida
      • Orlando, Florida, United States, 32806
        • Recruiting
        • Orlando Health Cancer Institute (Melanoma/NSCLC)
        • Contact:
        • Principal Investigator:
          • Tirrell T. Johnson, MD
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • James Graham Brown Cancer Center (Melanoma/NSCLC)
        • Contact:
        • Principal Investigator:
          • Jason Chesney, MD, PhD
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering (Melanoma/NSCLC)
        • Principal Investigator:
          • Alexander Shoushtari, MD
        • Contact:
          • NSCLC
          • Phone Number: 6464979163
        • Contact:
          • Melanoma
          • Phone Number: 6464979067
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The Ohio State University
        • Principal Investigator:
          • Timothy Burns, MD
        • Contact:
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Recruiting
        • Allegheny Research Institute (Melanoma/NSCLC)
        • Contact:
        • Principal Investigator:
          • Thomas Curley, MD
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • M.D. Anderson Cancer Center (Melanoma/NSCLC)
        • Contact:
        • Principal Investigator:
          • Rodabe Amaria, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 or relapsed refractory metastatic non-small cell lung cancer (NSCLC).

  3. Cohort and indication specific criteria as follows:

    1. Phase 1 and Phase 2 Cohort 1 (enrollment complete):

      • Participants with unresectable or metastatic melanoma must have 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.
      • Participants with melanoma must not exceed 2 prior lines of systemic therapy. Neoadjuvant/Adjuvant treatment will not be considered a prior line of systemic therapy unless the participant progressed during or within the 12 weeks after the last dose of the adjuvant PD-1/PD-L1 blocking antibody.

    2. Phase 1 and Phase 2 Cohort 2 (recruiting):

      • 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).
      • Participant must not have been exposed to any second line cytotoxic chemotherapy if they have already received cytotoxic chemotherapy in the first line setting.

    3. Phase 2 Cohort 3 (recruiting):

      • Participants with unresectable or metastatic melanoma must have 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.
      • Participants with melanoma must not exceed 2 prior lines of systemic therapy. Neoadjuvant/Adjuvant treatment will not be considered a prior line of systemic therapy unless the participant progressed during or within the 12 weeks after the last dose of the adjuvant PD-1/PD-L1 blocking antibody.
      • Participants with targetable BRAF mutations are not required to have received prior BRAF inhibitors. Participants must not have disease progression on a BRAF/MEK inhibitor that was given as the most recent line of therapy.

    4. Phase 2 Cohort 4 (recruiting):

      • Participants with frontline unresectable or metastatic melanoma.
      • Participants may have received up to 2 doses of system therapy containing a programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) blocking antibody-based treatment of unresectable metastatic melanoma (but must not have known clinical progression.) Neoadjuvant/Adjuvant treatment will not be considered a prior line of systemic therapy; however, participants whose disease progressed within 12 weeks after the last dose of the PD-1/PD-L1 blocking antibody given as adjuvant treatment (primary ICI resistant) are not eligible.
  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 greater than 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 or its other genetic equivalents (e.g. GNA11 and GNAQ).
  2. Participant has a history of brain metastases or leptomeningeal disease. Participants may be considered for enrollment if they have 4 or fewer brain metastatic lesions that are that have been treated, if clinically indicated. Asymptomatic brain metastases that are equivocal or too small to warrant treatment may not be counted towards the above set limits upon discussion and agreement from the Medical Monitor.
  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 engineered TIL cell therapy is allowed.
  9. Participant requires systemic steroid therapy of greater than10 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Participants with advanced solid tumors
Participants will receive conditioning therapy prior to administration of 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 short courses of acetazolamide.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
28 Days
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 Blinded Independent Central Review (BICR) 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 Cohort 3)
2 years
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 Cohort 1, 2, and 4)
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
2 years
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)
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Obsidian Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 25, 2023

Primary Completion (Estimated)

June 30, 2029

Study Completion (Estimated)

June 30, 2029

Study Registration Dates

First Submitted

September 22, 2023

First Submitted That Met QC Criteria

September 28, 2023

First Posted (Actual)

September 29, 2023

Study Record Updates

Last Update Posted (Actual)

May 1, 2026

Last Update Submitted That Met QC Criteria

April 27, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OBX115-23-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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