52 Participants Needed

OBX-115 for Skin Cancer

(Agni-01 Trial)

Recruiting at 16 trial locations
OT
Overseen ByObsidian Therapeutics
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: Obsidian Therapeutics, Inc.
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment called OBX-115 for adults with advanced solid tumors. It aims to see if the treatment is safe and effective by measuring its ability to shrink tumors, control disease progression, and improve survival.

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.

What data supports the effectiveness of the treatment OBX-115 for skin cancer?

Research shows that IL15, a component of the treatment, can boost the immune system's T-cells and natural killer cells, which are important for fighting cancer. This has been effective in other cancer treatments, suggesting potential benefits for skin cancer as well.12345

What safety data exists for OBX-115 or similar treatments in humans?

CAR T-cell therapies, like OBX-115, have shown significant potential in treating various cancers but can cause serious side effects such as cytokine release syndrome (CRS) and neurological toxicities. These treatments are being improved with safety measures like the inducible Caspase 9 'safety switch' to manage these risks.678910

What makes the OBX-115 treatment for skin cancer unique?

OBX-115 is unique because it uses genetically modified T cells that include IL-15, a powerful immune stimulator, to enhance the persistence and effectiveness of the T cells in fighting cancer, potentially reducing toxicity compared to other treatments.1261112

Eligibility Criteria

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.
See 8 more

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.
See 7 more

Timeline

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

Treatment Details

Interventions

  • OBX-115
Trial OverviewThe 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.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Participants with advanced solid tumorsExperimental Treatment1 Intervention
Participants will receive conditioning therapy prior to administration of OBX-115 regimen.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Obsidian Therapeutics, Inc.

Lead Sponsor

Trials
1
Recruited
50+

Findings from Research

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.
IL15 and T-cell Stemness in T-cell-Based Cancer Immunotherapy.Pilipow, K., Roberto, A., Roederer, M., 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.
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]
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.
Manufacture of gene-modified human T-cells with a memory stem/central memory phenotype.Gomez-Eerland, R., Nuijen, B., Heemskerk, B., et al.[2021]

References

IL15 and T-cell Stemness in T-cell-Based Cancer Immunotherapy. [2021]
Co-expression IL-15 receptor alpha with IL-15 reduces toxicity via limiting IL-15 systemic exposure during CAR-T immunotherapy. [2022]
Manufacture of gene-modified human T-cells with a memory stem/central memory phenotype. [2021]
Update on immunotherapy for melanoma. [2019]
Stability and activity of MCSP-specific chimeric antigen receptors (CARs) depend on the scFv antigen-binding domain and the protein backbone. [2015]
IL-12 secreting tumor-targeted chimeric antigen receptor T cells eradicate ovarian tumors in vivo. [2021]
Induction of Neoantigen-Specific Cytotoxic T Cells and Construction of T-cell Receptor-Engineered T Cells for Ovarian Cancer. [2022]
Cross-study safety analysis of risk factors in CAR T cell clinical trials: An FDA database pilot project. [2022]
Building safety into CAR-T therapy. [2023]
The CAR-HEMATOTOX risk-stratifies patients for severe infections and disease progression after CD19 CAR-T in R/R LBCL. [2022]
11.United Statespubmed.ncbi.nlm.nih.gov
Tumor specific cytolysis by tumor infiltrating lymphocytes in breast cancer. [2019]
12.United Statespubmed.ncbi.nlm.nih.gov
Eradication of Neuroblastoma by T Cells Redirected with an Optimized GD2-Specific Chimeric Antigen Receptor and Interleukin-15. [2020]