Program Evaluating TIDAL-01 in Solid Tumors Has Been Discontinued

The decision impacts the phase 1 STARLING trial and additional phase 1 trials sponsored by the Moffitt Cancer Center evaluating TIDAL-01 in solid tumors.

The program evaluating selected tumor infiltrating lymphocyte (TIL) therapy, TIDAL-01, in solid tumors has been halted for further development, and all clinical trials evaluating TIDAL-01 have been discontinued, according to a news release from the drug’s developer, Turnstone Biologics.¹

The decision impacts the phase 1 STARLING trial (NCT05576077) and additional sponsored phase 1 trials with the Moffitt Cancer Center, which all evaluated TIDAL-01 in solid tumors. ² Turnstone’s management and board of directors have launched a process to evaluate strategic alternatives.

“Manufacturing for our selected TIL therapy requires continued investment in process improvements,” Sammy Farah, MBA, PhD, president and chief executive officer of Turnstone Biologics, said in the news release on the program halt.¹ “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 and to conclude all clinical studies evaluating the program in solid tumors.”

Phase 1 STARLING Trial

The phase 1 STARLING trial assigned patients with advanced solid tumors to receive TIDAL-01 following ex vivo expansion of tumor reactive TIL population after preparation with non-myeloablative lymphodepletion chemotherapy and low-dose radiation.³ Additionally, pembrolizumab (Keytruda) was given following TIL infusion and continued every 3 to 6 weeks for a maximum of 2 years.

The primary end point of the study was the safety and tolerability of TIDAL-01. Secondary end points included objective response rate (ORR), disease control rate (DCR), and duration of response (DOR).

As of the data cutoff date of July 15, 2024, in 4 evaluable patients with microsatellite stable (MSS) metastatic colorectal cancer (CRC), the ORR was 25%, and the DCR was 50%. A deep and durable ongoing complete response (CR) was observed in 1 patient. Additionally, the regimen elicited a clinical benefit rate (CBR) of 50%, with 1 patient experiencing progression-free survival (PFS) over 1 year following CR, and another patient with stable disease experiencing PFS after 6 months.

Furthermore, TIDAL-01 was found to be well tolerated, and safety data were consistent with known adverse effects (AEs) associated with lymphodepletion, as well as IL-2 and pembrolizumab, as of data cutoff. The target dose of at least 1 x 10⁹ total T cells was exceeded in all manufactured CRC products.

Moffitt Cancer Center–Sponsored Study

An investigator-sponsored phase 1 study (NCT05628883) conducted at Moffitt Cancer Center aimed to assess the feasibility, efficacy, and safety of TIDAL-01 in patients with unresectable or metastatic melanoma.⁴ Patients were assigned to receive TIDAL-01 in combination with cyclophosphamide, fludarabine, and IL-2.

The study’s primary end point was the percentage of patients who successfully received TIDAL-01 following tumor resection. Secondary end points included ORR, overall survival, progression-free survival, and durable response rate.

Patients 18 to 75 years old with histologically confirmed, unresectable or metastatic melanoma and progression on or intolerance of standard-of-care therapy were eligible for enrollment on the trial. Additional eligibility criteria included having an ECOG performance status of 0 or 1 and adequate organ and marrow function. Those with prior cell therapy or a primary immunodeficiency disorder were ineligible for enrollment.

“I would like to convey our deepest gratitude to the patients, investigators, and collaborators for their participation in our clinical development efforts,” Farah concluded in the news release.¹ “I also wish to sincerely thank the Turnstone team members who worked tirelessly on this program, and our shareholders for their commitment to [Turnstone].”

References

1. Turnstone Biologics announces plans to explore strategic alternatives. News release. Turnstone Biologics. February 4, 2025. Accessed February 5, 2025. https://tinyurl.com/5etrmavs
2. Turnstone Biologics Corp. reports positive initial data from phase 1 trial of TIDAL-01 in metastatic colorectal cancer. Turnstone Biologics. August 15, 2024. Accessed February 5, 2025. https://tinyurl.com/yyfsj2fb
3. A study of TBio-4101 (TIL) and pembrolizumab in patients with advanced solid tumors (STARLING). ClinicalTrials.gov. Updated January 8, 2025. Accessed February 5, 2025. https://tinyurl.com/3hxk9fm7
4. Proof of concept of TBio-4101, lymphodepleting chemo, IL-2 for relapsed/​refractory melanoma. ClinicalTrials.gov. Updated January 22, 2025. Accessed February 5, 2025. https://tinyurl.com/3fh8zfdt