NEW YORK – Tizona Therapeutics on Thursday said it has begun testing a combination regimen involving its human leukocyte antigen (HLA)-G-targeted antibody TTX-080 in biomarker-selected colorectal cancer patients within an ongoing Phase Ib trial.
The multi-arm trial, started in 2020, is testing the activity of TTX-080 as a monotherapy, as well as in combination with Eli Lilly's EGFR inhibitor Erbitux (cetuximab), Merck's checkpoint inhibitor Keytruda (pembrolizumab), and chemotherapy in patients with various advanced solid tumors. In two recently added randomized arms, Tizona said it is comparing the activity of TTX-080 plus Erbitux and FOLFIRI versus Erbitux and FOLFIRI alone in metastatic colorectal cancer patients who have previously received 5-FU and oxaliplatin in the frontline or adjuvant setting but relapsed within six months.
To participate in the new trial arms, patients with metastatic colorectal cancers must have tumors that are microsatellite stable, Ras wild-type, BRAF wild-type, and HER2 negative. Investigators will track overall response rate as the primary endpoint in the trial and safety, duration of response, median progression-free survival, and median overall survival as secondary endpoints.
HLA-G is expressed during pregnancy and plays a role in allowing the mother's immune system to tolerate the fetus. In cancer, expression of HLA-G enables tumor cells to evade the immune system. TTX-080 is designed to block the interaction of HLA-G with its ligands ILT2 and ILT4, blocking suppression of the immune response.
In an early analysis from the trial presented at the American Society of Clinical Oncology's annual meeting in June, among 14 patients with wild-type Ras, wild-type BRAF, HER2-negative metastatic colorectal cancer who received TTX-080 and Erbitux, four patients responded, another four patients had a partial response, and six patients had stable disease. Patients in this group had received a median of two prior lines of treatment, including chemotherapy but not an EGFR inhibitor.
A positive readout from this Phase Ib trial could lead to a big payout for the South San Francisco, California-based company. Gilead Sciences acquired a 49.9 percent equity interest in Tizona in 2020 and has the option to acquire the remaining equity interest in the firm for up to an additional $1.25 billion. Gilead may acquire the remaining shares of Tizona following completion of the study, or earlier at its discretion.