TIDAL-01 will be evaluated in patients with advanced or metastatic breast carcinoma, colorectal adenocarcinoma, or uveal melanoma.
Turnstone Biologics’ TIDAL-01 (TBio-4101), an investigational selected tumor infiltrating lymphocyte (TIL) therapy intended to treat various types of solid tumors, has received clearance of its investigational new drug (IND) application by the FDA.1
TIDAL-01 consists of autologous tumor-reactive T-cells that have been selected based on potency for expansion with the use of tumor specific antigens. The IND clearance will allow Turnstone Biologics to initiate the planned multicenter, phase 1 STARLING clinical trial (NCT05576077) which will evaluate TIDAL-01 for the treatment of patients with several types of advanced solid tumors with varying mutational burden. This will be the second clinical trial involving TIDAL-01, as Turnstone Biologics’ previously received IND clearance in July of this year for a separate phase 1 clinical trial evaluating TIDAL-01 in patients with cutaneous and non-cutaneous melanoma, which is being carried out in collaboration with Moffitt Cancer Center.2
“Clearance of our IND is a critical milestone for Turnstone in the advancement of our novel TIL therapy pipeline,” Sammy Farah, PhD, president and chief executive officer, Turnstone Biologics, said in a statement regarding the news.1 “TIDAL-01 is a potentially transformative approach to improving the potency of TILs and bringing the clinical benefit of Selected TILs to patients with solid tumor cancers where the unmet medical need is high. We are eager to commence the clinical study for TIDAL-01 and to progress this candidate through the clinic.”
The open-label STARLING trial is expected to enroll approximately 30 patients aged 18 years to 70 years with advanced or metastatic breast carcinoma, colorectal adenocarcinoma, or uveal melanoma which failed or was refractory to standard of care therapy. Participants are required to have at least 1 lesion that can be used for response assessments, at least 1 tumor amenable to tissue harvesting for TIL manufacturing, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate organ function. Patients who have past or current ischemic heart disease or clinically significant atrial/ventricular rhythm abnormality (without cardiac clearance); have brain metastasis; have primary or acquired immunodeficiency disorders; have a history of cell therapy or organ transplant; have a history of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, IL-2, or pembrolizumab, or any of their constituents; are on chronic anti-coagulant therapy; have a left ventricular ejection fraction less than or equal to 45%; have a New York Heart Association classification greater than 1; or have a forced expiratory volume less than or equal to 60% of predicted value and a corrected diffusing capacity for carbon monoxide less than 60% of predicted value will be excluded from the study. Additional inclusion and exclusion criteria exist.
Participants will receive non-myeloablative chemotherapy prior to TIL infusion and will be administered IL-2 along with TIDAL-01. After TIDAL-01 infusion and the resolution of IL-2 toxicities patients will receive pembrolizumab every 3 weeks for up to 2 years. The study’s primary end point is the incidence of treatment-emergent adverse events. Secondary end points include the overall response rate for all patients and for each indication, the estimated disease control rate, and the estimated duration of response. The study is expected to begin before the end of the year and has an estimated completion date of June 30, 2024.
“To achieve success against solid tumors, we are applying a differentiated approach with TILs to overcome what we believe to be the greatest barrier to more effective cell therapies: the low amount of T-cells that recognize and attack the tumor,” Stewart Abbot, PhD, chief scientific officer, Turnstone Biologics, added to the statment.1 “In identifying, selecting and expanding these tumor-reactive T-cells, we aim to drive more potent solid tumor killing and improved clinical outcomes in multiple different cancer indications.”