OBX-115 for Skin Cancer

(Agni-01 Trial)

Recruiting at 17 trial locations

Overseen By Obsidian Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Obsidian Therapeutics, Inc.

Must not be taking: Systemic steroids

Disqualifiers: Brain metastases, Immunodeficiency, Organ transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

52 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called OBX-115, a modified T cell therapy, for individuals with advanced skin cancer, specifically melanoma, or a type of lung cancer known as non-small cell lung cancer (NSCLC). The goal is to determine if OBX-115 is safe and effective for those whose cancer has worsened despite previous treatments. It suits individuals with melanoma who have tried other treatments or those with NSCLC who haven't responded to standard therapies. Participants should have a measurable tumor for developing the treatment. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy greater than 10 mg/day of prednisone or equivalent, you may not be eligible to participate.

Is there any evidence suggesting that OBX-115 is likely to be safe for humans?

Research shows that OBX-115, a new treatment for advanced solid tumors, appears promising in safety studies. Early research suggests that OBX-115 enhances the function and longevity of certain immune cells, called TILs, which might help control tumors. Importantly, these studies did not use IL-2, a substance that can sometimes cause side effects, potentially making OBX-115 gentler on the body.

While detailed safety data from trials are not yet available, the treatment's progression to Phase 1/2 offers some insights. In this phase, researchers closely monitor how well participants tolerate the treatment. OBX-115 has also received special recognition from the FDA, indicating potential benefits with manageable risks. Overall, while OBX-115 remains under study, early results suggest it is fairly well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for skin cancer, which often include surgery, radiation, or chemotherapy, OBX-115 is unique because it aims to harness the body's own immune system to fight cancer cells. This investigational treatment is exciting because it involves a new mechanism of action that could potentially target and eliminate cancer cells more precisely, reducing damage to healthy cells. Researchers are particularly interested in OBX-115 because it could offer a new avenue for patients with advanced solid tumors where traditional methods have limited effectiveness.

What evidence suggests that OBX-115 might be an effective treatment for skin cancer?

Research has shown that OBX-115, which participants in this trial will receive, is a promising treatment for advanced solid tumors. OBX-115 uses specially designed immune cells called tumor-infiltrating lymphocytes (TILs) to find and attack cancer cells. Unlike other TIL therapies, OBX-115 does not require additional harmful drugs, potentially making it safer. Early results indicate that this therapy uses a protein called IL-15, which helps immune cells grow, to increase its effectiveness. These engineered cells have demonstrated positive results in similar cancers, such as advanced melanoma. Overall, OBX-115's unique method could offer new hope for people with difficult-to-treat cancers. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults with advanced melanoma resistant to immune checkpoint inhibitors can join. They must have had disease progression after specific systemic therapies, at least one resectable lesion for OBX-115 generation, and be in good health otherwise. Participants need proper organ function, an ECOG status of 0 or 1, and agree to use contraception.

Inclusion Criteria

My cancer progressed after treatment with PD-1/PD-L1 inhibitors and, if applicable, BRAF/MEK inhibitors.

I have at least one tumor that can be measured after a biopsy.

I can care for myself and doctors expect me to live more than 6 months.

Exclusion Criteria

You have a weakened immune system, either from birth or from getting sick.

I have had cancer spread to my brain or its coverings.

I need more than 10 mg/day of prednisone or a similar medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Therapy

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

1-2 weeks

Treatment

Participants receive the OBX-115 regimen and are monitored for dose-limiting toxicities

4 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of response and adverse events

2 years

What Are the Treatments Tested in This Trial?

Interventions

• OBX-115

Trial Overview

The trial is testing the safety and effectiveness of a new treatment called OBX-115 on adults with advanced melanoma that hasn't responded to previous treatments including PD-1/PD-L1 blockers and possibly BRAF/MEK inhibitors.

How Is the Trial Designed?

Group I: Participants with advanced solid tumors Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Obsidian Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

50+

Published Research Related to This Trial

CAR-T therapy has shown significant success in treating relapsed/refractory B-cell malignancies, utilizing genetically modified T-cells to target and eliminate cancer cells effectively.

Despite its efficacy, CAR-T therapy is associated with serious toxicities such as cytokine release syndrome and neurotoxicity, necessitating improved safety measures, especially as the therapy is being tested in solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Building safety into CAR-T therapy. Peters, DT., Savoldo, B., Grover, NS.[2023]

IL15 is a powerful cytokine that enhances the immune response by boosting T-cells and natural killer (NK) cells, showing promise for improving cancer treatments through adoptive T-cell transfer.

Clinical trials have demonstrated that IL15 can significantly increase the activity of NK and CD8(+) memory T cells, suggesting its potential as a key component in T-cell-based immunotherapy for cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL15 and T-cell Stemness in T-cell-Based Cancer Immunotherapy. Pilipow, K., Roberto, A., Roederer, M., et al.[2021]

Incorporating the IL15 cytokine into the CAR construct (GD2.CAR.15) significantly enhances the survival and antitumor activity of T cells against neuroblastoma, showing improved performance compared to the standard GD2.CAR-T cells in both laboratory and animal models.

The engineered GD2.CAR.15-T cells exhibited reduced PD-1 expression and a stem cell-like phenotype, which contributed to their superior effectiveness, while also including a safety switch (iC9) that allows for controlled elimination of these cells if necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eradication of Neuroblastoma by T Cells Redirected with an Optimized GD2-Specific Chimeric Antigen Receptor and Interleukin-15. Chen, Y., Sun, C., Landoni, E., et al.[2020]

The CAR-HEMATOTOX (HT) score effectively identifies patients at high risk for severe infections after CD19 CAR-T therapy, with high-risk patients experiencing a significantly higher rate of severe infections (40% vs 8%) and worse survival outcomes.

Prophylactic antibacterial treatment significantly reduced severe bacterial infections in high-risk patients, highlighting the importance of monitoring and preventive care for those identified as high risk before undergoing CAR-T therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The CAR-HEMATOTOX risk-stratifies patients for severe infections and disease progression after CD19 CAR-T in R/R LBCL. Rejeski, K., Perez, A., Iacoboni, G., et al.[2022]

The study successfully developed a rapid 2-week protocol to create neoantigen-specific TCR-engineered T cells from ovarian cancer patients, demonstrating the feasibility of this approach for advanced cancers.

While the engineered T cells showed effective cytotoxic activity against neoantigens, one case exhibited cross-reactivity with a wild-type peptide, highlighting the need for careful validation to prevent potential immune-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of Neoantigen-Specific Cytotoxic T Cells and Construction of T-cell Receptor-Engineered T Cells for Ovarian Cancer. Matsuda, T., Leisegang, M., Park, JH., et al.[2022]

High doses of interleukin-2 and various experimental immunotherapy strategies can lead to prolonged responses in patients with metastatic melanoma, indicating their potential effectiveness in treatment.

The development of these immunotherapy approaches is based on a deeper understanding of immune system activation, which may enhance the ability to target tumors and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on immunotherapy for melanoma. Ribas, A.[2019]

The study identified a second-generation CAR targeting MCSP that showed higher and more prolonged expression in T cells, leading to improved anti-tumor activity against melanoma cells.

T cells modified with this CAR not only increased survival in mice with melanoma but also effectively lysed tumor cells and released pro-inflammatory cytokines after being transfected from late-stage melanoma patients, suggesting strong potential for clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stability and activity of MCSP-specific chimeric antigen receptors (CARs) depend on the scFv antigen-binding domain and the protein backbone. Krug, C., Birkholz, K., Paulus, A., et al.[2015]

This study shows that tumor infiltrating lymphocytes (TIL) and effusion-associated mononuclear cells (EAMNC) from breast cancer patients can be significantly expanded in vitro using recombinant interleukin-2 (rIL-2), achieving over 300-fold proliferation while retaining their ability to target and kill autologous tumor cells.

The activated CD3+CD8+ T-lymphocytes demonstrated specific cytotoxicity against the patient's own tumor cells, indicating their potential for use in immunotherapy for advanced breast cancer, as they maintain both autologous tumor-specific and MHC-restricted cytotoxic activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor specific cytolysis by tumor infiltrating lymphocytes in breast cancer. Baxevanis, CN., Dedoussis, GV., Papadopoulos, NG., et al.[2019]

The study developed a novel CAR T cell therapy targeting the MUC-16ecto antigen in ovarian cancer, showing that the addition of IL-12 enhances T cell proliferation and IFNγ secretion, leading to improved antitumor efficacy in mouse models.

To ensure safety in potential clinical applications, the CAR T cells include an elimination gene that allows for their removal in case of unexpected side effects, making this approach both innovative and cautious.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-12 secreting tumor-targeted chimeric antigen receptor T cells eradicate ovarian tumors in vivo. Koneru, M., Purdon, TJ., Spriggs, D., et al.[2021]

CAR-T cells engineered to overexpress IL-15 showed improved viability and anti-tumor effects, but also led to serious liver injuries and lower survival rates in mouse models, indicating potential toxicity issues.

Combining IL-15 with IL-15 receptor alpha (IL-15Ra) in CAR-T cells reduced cytokine release and improved mouse survival while still effectively inhibiting tumor growth, suggesting a way to enhance the safety and efficacy of CAR-T therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Co-expression IL-15 receptor alpha with IL-15 reduces toxicity via limiting IL-15 systemic exposure during CAR-T immunotherapy. Zhang, Y., Zhuang, Q., Wang, F., et al.[2022]

In a study involving 1,926 subjects from 17 clinical trials, patients with acute lymphocytic leukemia (ALL) were found to have a higher risk of severe cytokine release syndrome (sCRS) and severe neurological toxicities (sNTX) compared to those with non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM).

The use of CAR T cells produced with gammaretrovirus vectors containing CD28 sequences was linked to increased rates of sNTX, while administering cytokine-directed therapies and corticosteroids at lower toxicity grades was associated with reduced rates of sCRS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cross-study safety analysis of risk factors in CAR T cell clinical trials: An FDA database pilot project. Foster, M., Negash, Y., Eberhardt, L., et al.[2022]

A new GMP protocol has been developed to produce T-cell receptor (TCR) gene-modified T-cells with an early memory phenotype, which may enhance their effectiveness in recognizing and attacking cancer cells.

These T-cells, generated using a combination of anti-CD3/CD28 stimulation and expansion with IL-7 and IL-15, are now being tested in a phase I/IIa clinical trial for advanced melanoma, marking a novel approach in T-cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Manufacture of gene-modified human T-cells with a memory stem/central memory phenotype. Gomez-Eerland, R., Nuijen, B., Heemskerk, B., et al.[2021]

Citations

1.

obsidiantx.com

obsidiantx.com/our-lead-clinical-program/

OBX-115 | Investigational IL2-free TIL therapy with mbIL15 ...

... advanced melanoma and non-small cell lung cancer (Agni-01). Agni-01: Multi-Center Advanced Solid Tumors Clinical Trial: NCT06060613. US study sites are ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06060613

Safety and Efficacy of OBX-115 in Advanced Solid Tumors

Participant has a histologically confirmed diagnosis of advanced/metastatic melanoma ore relapsed refractory metastatic non-small cell lung cancer (NSCLC).

3.

mskcc.org

mskcc.org/cancer-care/clinical-trials/24-057

A Phase 1/2 Study of OBX-115 Cell Therapy and ...

... Efficacy of Membrane Bound IL-15 Expressing Tumor-Infiltrating Lymphocytes (OBX-115) In Participants with Advanced Solid Tumors. Purpose. The purpose of this ...

4.

obsidiantx.com

obsidiantx.com/news-releases/obsidian-therapeutics-to-present-clinical-data-from-obx-115-its-engineered-til-cell-therapy-for-patients-with-advanced-melanoma-in-oral-presentation-at-the-2025-asco-annual-meeting/

News

Title: OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy with regulatable membrane-bound IL15 (mbIL15) in patients (pts) with immune ...

5.

meetings.asco.org

meetings.asco.org/abstracts-presentations/246566

OBX-115 engineered tumor-infiltrating lymphocytes (TIL) ...

Obsidian Therapeutics, Inc. Background: Non-engineered TIL cell therapy is approved for ICI-resistant advanced melanoma, but requires co-administration of toxic ...

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S1525001625003107

IL-2-independent expansion, persistence, and antitumor ...

Our findings support the clinical evaluation of this first IL-2-free TIL product (OBX-115) in ongoing phase 1/2 trials in patients with advanced ...

7.

targetedonc.com

targetedonc.com/view/fda-grants-rmat-designation-to-novel-til-therapy-obx-115-in-melanoma

FDA Grants RMAT Designation to Novel TIL Therapy OBX- ...

OBX-115, a novel TIL therapy, has been granted FDA RMAT designation in unresectable or metastatic melanoma resistant to ICI therapy.