Coherus Oncology reported interim results from its TREGCHECK clinical program testing tagmokitug, an investigational antibody, with the immune-oncology drug toripalimab, sometimes alongside chemotherapy. The most notable early activity was in first-line esophageal cancer, where the three-drug combination produced a high response rate in a small group of evaluable patients. The company plans to expand both first- and second-line esophageal cancer cohorts and continue tracking responses, survival measures and biomarkers.
Key clinical results
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First-line esophageal squamous cell carcinoma (ESCC): In the Phase 1b study, patients received tagmokitug with toripalimab, 5-fluorouracil and cisplatin. At the October 14 data cutoff, 8 patients were evaluable for efficacy: 6 had confirmed responses, for a 75% confirmed overall response rate. One patient had a confirmed complete response. The confirmed response rate was 100% among PD-L1-positive patients, though the company did not provide the number of patients in that subgroup in the reported results.
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Additional responses after the cutoff: After the October 14 cutoff, a previously unconfirmed partial response was confirmed and a newly evaluable patient had a confirmed partial response. That brought the response rate to 8 of 9 evaluable patients, or 89%. These later results were not part of the original cutoff dataset.
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Second-line ESCC: Patients whose cancer had returned or spread after first-line chemotherapy were randomized to receive one of two tagmokitug doses with toripalimab. At the cutoff, 17 patients had been assessed for safety, but only 8 were evaluable for efficacy—2 in the 300-mg group and 6 in the 700-mg group. In the 700-mg group, 1 of 6 patients had a confirmed response and 2 of 6 had clinical benefit, including durable stable disease. Median progression-free survival was 5.5 months in that group. The company cited about 3.4 months as a U.S. standard-of-care chemotherapy benchmark; the small, early-stage dataset does not establish a comparative treatment benefit.
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Other tumor types: The program also reported interim activity in several settings:
- In second-line head and neck cancer, 23 HPV-positive patients across the two dose groups had a 13% confirmed response rate and a 26.1% clinical benefit rate. Among the 11 HPV-positive patients who also scored positive on the company’s tumor immune regulatory index biomarker, the clinical benefit rate was 45%. The biomarker is being evaluated as a possible way to identify patients more likely to benefit.
- In upper gastrointestinal cancers, including gastric, gastroesophageal junction and esophageal adenocarcinoma, 4 of 17 evaluable patients in the 700-mg group had confirmed partial responses. Two responses were in esophageal adenocarcinoma. Coherus said activity was seen in both patients previously treated with PD-1 drugs and those who had not received them; follow-up is continuing.
- In heavily pretreated microsatellite-stable colorectal cancer, 1 of 17 evaluable patients had a confirmed response and 2 had clinical benefit. The company also reported molecular responses measured through circulating tumor DNA.
Safety and next steps
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Across 33 patients who received tagmokitug alone, no dose-limiting toxicities were reported through doses of 1,200 mg every three weeks. In more than 120 patients treated with tagmokitug plus toripalimab, Coherus reported no new safety signals beyond those associated with PD-1 immunotherapy. No treatment-related deaths were reported.
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Among 120 patients who received the combination, immune-related adverse events occurred in 40%; 20% had Grade 3–5 immune-related events. The most commonly reported treatment-related side effects were infusion reactions (25%), fatigue (19.2%) and rash (15.8%). In the 10-patient first-line ESCC group receiving chemotherapy as well, the company reported no new safety signals or Grade 5 treatment-emergent events.
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Coherus plans to expand enrollment in both first- and second-line ESCC and continue evaluating response durability, progression-free survival and biomarker results. It is also planning a study of tagmokitug with a T-cell engager in metastatic castration-resistant prostate cancer.
What the results mean
The first-line ESCC response figures are encouraging but come from a very small, ongoing early-phase study; only eight patients were included in the initial efficacy analysis. The later 89% figure is based on nine evaluable patients and includes data confirmed after the cutoff. Tagmokitug and toripalimab remain investigational for these uses, and the results do not establish safety or effectiveness or show that the regimen is superior to approved treatment.