Turnstone Biologics announced the discontinuation of its TIDAL-01 development program, a selected tumor infiltrating lymphocyte (TIL) therapy for solid tumors, despite showing promising early clinical results. The company cited manufacturing challenges and financial constraints as key factors in this strategic decision.
Early Clinical Promise Cut Short
The phase 1 STARLING trial (NCT05576077) demonstrated encouraging results before its termination. Among four evaluable patients with microsatellite stable (MSS) metastatic colorectal cancer, the therapy achieved a 25% objective response rate and a 50% disease control rate. Notably, one patient experienced a deep and durable complete response, maintaining progression-free survival for over one year.
The treatment regimen combined TIDAL-01 with pembrolizumab following lymphodepletion chemotherapy and low-dose radiation. Safety data aligned with expected adverse effects associated with lymphodepletion, IL-2, and pembrolizumab administration. All manufactured colorectal cancer products successfully exceeded the target dose of 1 x 109 total T cells.
Manufacturing Challenges and Financial Realities
"Manufacturing for our selected TIL therapy requires continued investment in process improvements," explained Sammy Farah, MBA, PhD, president and CEO of Turnstone Biologics. "Due to these capital-intensive requirements and after careful review of future funding needs and the current financial markets, [Turnstone] has decided to discontinue development of TIDAL-01."
Broader Impact on Clinical Development
The discontinuation affects multiple clinical trials, including a Moffitt Cancer Center-sponsored phase 1 study (NCT05628883) investigating TIDAL-01 in unresectable or metastatic melanoma patients. This study aimed to evaluate the therapy in combination with cyclophosphamide, fludarabine, and IL-2 in patients who had progressed on or were intolerant to standard-of-care treatments.
Strategic Implications
Turnstone's management and board of directors have initiated a process to evaluate strategic alternatives following this development. The decision represents a significant setback in the field of TIL therapy development, particularly for patients with limited treatment options in solid tumors.
"I would like to convey our deepest gratitude to the patients, investigators, and collaborators for their participation in our clinical development efforts," Farah stated, acknowledging the impact of this decision on the oncology community.
