STCube begins patient dosing in combo trial for immunotherapy-resistant colorectal cancer

STCube has kicked off patient dosing in a phase 1b/2 trial of its experimental immunotherapy nelmastobart, marking the first clinical use of BTN1A1 as a biomarker in microsatellite stable (MSS) colorectal cancer -- a notoriously immunotherapy-resistant subtype.

The Korean biotech said Friday that two patients in the first cohort received nelmastobart at 800 mg in combination with trifluridine-tipiracil at 35 mg/m² and bevacizumab at 5 mg/kg.

The triplet regimen blends checkpoint inhibition, chemotherapy, and anti-angiogenesis in an effort to overcome resistance in the third-line metastatic setting.

“The majority of MSS colorectal cancer patients have few immunotherapy options,” CEO Jung Hyun-jin said in a Friday statement. “With nelmastobart, we’re targeting a new mechanism that may convert immunologically ‘cold’ tumors into responsive ones.”

The trial enrolls patients who are refractory or intolerant to standard oxaliplatin- and irinotecan-based chemotherapies. 

TAS-102 plus bevacizumab is an approved standard in this setting. But real-world data from Samsung Medical Center suggest the combo offers only modest benefits, with a median progression-free survival (PFS) of 3.3 months and objective response rate (ORR) of 8.4 percent. That’s compared to 2.5 months and 5.4 percent for TAS-102 alone.

STCube is hoping to improve on that, using BTN1A1 -- an emerging immune checkpoint protein in the B7 family -- as a stratification tool. The first part of the trial will assess safety, pharmacokinetics, dose-limiting toxicities and early efficacy in 6 to 18 patients.

A phase 2 expansion is planned for 52 patients with high BTN1A1 expression. 

Previous data offer some early encouragement. In a phase 1b investigator-initiated study, nelmastobart combined with capecitabine showed a 16.7 percent ORR and 100 percent disease control rate in MSS tumors, a population historically unresponsive to checkpoint inhibitors.

BTN1A1 expression is seen in roughly 40 percent of colorectal cancers, STCube said, and could become a foundation for precision immunotherapy if clinical efficacy holds up.

The company emphasized that the trial’s manufacturing and biomarker protocols were aligned with international standards to support global licensing talks already underway.

The trial is being conducted at five major Korean hospitals, including Asan Medical Center, Seoul National University Hospital, and Severance Hospital.

It will also explore nelmastobart in additional solid tumor types including head and neck squamous cell carcinoma (HNSCC), nasopharyngeal carcinoma (NPC), and chordoma, a rare bone cancer of the spin -- all known for low immunotherapy response rates.