Turnstone Biologics Announces Positive Phase 1 Data for TIDAL-01 in Metastatic Colorectal Cancer

Turnstone Biologics Corp. (Turnstone), a clinical-stage biotechnology company, has announced encouraging initial results from its Phase 1 STARLING trial of TIDAL-01 in patients with metastatic microsatellite stable colorectal cancer (MSS mCRC). The study aims to explore the safety, tolerability, and clinical efficacy of TIDAL-01, a novel Selected Tumor-Infiltrating Lymphocyte (Selected TIL) therapy designed to treat solid tumors.

The STARLING trial is ongoing and involves multiple sites. It is a non-randomized, open-label, single-dose study. As of July 15, 2024, the trial has enrolled patients with colorectal cancer, head and neck squamous cell carcinoma, and uveal melanoma. Initial data from the trial has shown promising results in the MSS mCRC patient group.

Key Findings:
1. Clinical Responses: Among the initial four evaluable MSS mCRC patients, Turnstone reported a 25% overall response rate (ORR) and a 50% disease control rate (DCR). Notably, one patient achieved a deep and durable complete response (CR).

2. Durability of Response: Half of the patients experienced sustained clinical benefits. The patient with an ongoing complete response achieved progression-free survival extending beyond one year, while another patient with stable disease saw a progression-free survival of six months.

3. Translational Profile: TIDAL-01 therapy was able to generate high titer, polyclonal, multi-epitope tumor neoantigen-reactive T cells. These cells expanded within the patient, persisted in the bloodstream, and were correlated with increased CD8 T cell tumor infiltration.

4. Tolerability Profile: The treatment was generally well-tolerated. The observed adverse events were consistent with those associated with the lymphodepletion regimen and the administration of IL-2 and pembrolizumab.

5. Manufacturing Success: The manufacturing success rate for TIDAL-01 in colorectal cancer patients with sufficient starting material was 80%. This rate is consistent with other early-stage cell therapy processes. The target dose of at least 1x10⁹ total T cells was exceeded in all manufactured CRC products.

Turnstone's President and CEO, Sammy Farah, expressed optimism about these initial findings, highlighting the potential of TIDAL-01 to significantly improve treatment outcomes for patients with metastatic CRC and other solid tumors. According to Farah, the 25% ORR and 50% DCR observed with TIDAL-01 are promising compared to the standard of care for this patient population, which typically reports a 1-6% ORR and median progression-free survival (mPFS) of 2.0-5.6 months.

Interim Chief Medical Officer Mike Burgess added that CRC is one of the leading causes of cancer-related deaths in the United States. He emphasized the significance of TIDAL-01 as a potential therapeutic option for metastatic CRC patients. Burgess also noted that the patient who experienced a complete response remains in remission more than a year post-treatment. Turnstone will continue to evaluate the benefits of TIDAL-01 in CRC and other tumor types, such as uveal melanoma and head and neck cancer, through the STARLING study.

TIDAL-01, Turnstone’s lead Selected TIL therapy candidate, employs an unbiased identification and functional screening process to isolate and selectively expand the most comprehensive set of tumor-reactive TILs from the patient’s tumor. The production process aims to deliver a significantly higher proportion of functional and potent tumor-reactive T cells compared to bulk TIL. The Phase 1 studies, including the STARLING trials and those conducted in collaboration with Moffitt Cancer Center, are assessing the safety, biology, initial efficacy, and manufacturing feasibility of TIDAL-01 in patients with solid tumors where standard bulk TIL therapies have shown limited success.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the U.S. and ranks second in cancer-related mortality. In 2024, approximately 153,000 new CRC cases and 53,000 deaths are expected in the United States. About 85% of CRC cases are characterized as microsatellite stable (MSS), which are typically less responsive to immunotherapies compared to microsatellite instability-high (MSI-H) tumors. Current treatment options for advanced MSS mCRC, including chemotherapy and targeted therapies, have limited success, with low ORR and short median progression-free survival.

Turnstone Biologics aims to address these challenges through its innovative Selected TIL therapy, with ongoing research and development efforts focused on improving treatment outcomes for patients with high unmet needs in oncology.