A precision T-cell therapy stalls treatment-resistant cancers in clinical trial.
Researchers at NIH, Mass General Brigham and Memorial Sloan Kettering report that the experimental drug invika halted disease progression in most treatment-resistant solid tumor patients at its optimal dose in an early trial.
A phase 1/2 clinical trial of the experimental drug invikafusp alfa, known as invika, produced early signs that it can manage cancers that have resisted other treatments, including standard immunotherapy. The study was led by researchers at the National Institutes of Health, Mass General Brigham and Memorial Sloan Kettering, and was published in Nature Medicine on October 23, 2026. This was the first trial of the drug in humans.
Invika is a protein designed to engage only a small subset of T cells, specifically two groups of tumor-infiltrating lymphocytes. According to the release, other strategies to rally T cells usually do so indiscriminately, commonly causing severe side effects. Earlier preclinical work at the National Cancer Institute's Center for Cancer Research indicated that the drug stimulated anti-tumor activity in animal models.
The trial enrolled patients with a wide variety of cancers, most of which had not responded well to immune checkpoint blockade therapies. In phase 1, participants received different doses every two weeks so the team could assess safety and find the optimal dose. Several participants had flu-like side effects, which the researchers described as expected and generally manageable with additional medication and supportive care. Phase 2 then treated participants at the optimal dose.
Across both phases, 27 participants received the optimal dose. Their disease did not progress in 16 of them (59.3%). Four participants (14.8%) had tumor shrinkage of more than 30% in targeted tumors. Two of those four had metastatic colorectal cancer of a notoriously treatment-resistant type and were taking invika as a seventh-line therapy. Another had stage 4 non-small cell lung cancer that had resisted multiple therapies. At non-optimal doses, invika did not appear to offer significant benefit.
The authors found that the drug increased the target T-cell populations without affecting other T cells, and the four cases of tumor reduction matched the largest shifts in those populations. Immune activity alone did not always produce a measurable clinical response, as the authors expected at this stage. Co-first author Nicholas Tschernia said, “These results are early.” He added that the findings justify further study, particularly combinations with other cancer treatments. Co-corresponding author James Gulley described the approach as “a more precise means of stimulating anti-tumor immunity.”
The sponsor, Marengo Therapeutics, previously announced an FDA Fast Track designation for invika in antigen-rich metastatic colorectal cancer. The FDA has since granted the same designation for similar solid tumors after prior therapy, including checkpoint inhibitors. The trial is still enrolling participants.
At a Glance
- Of 27 participants treated at the optimal dose, disease did not progress in 16 (59.3%).
- Four participants (14.8%) had tumor shrinkage greater than 30%, including two with metastatic colorectal cancer on seventh-line therapy.
- Phase 1 gave varying doses of invika every two weeks to find the optimal dose before phase 2.
- The results appeared in Nature Medicine on October 23, 2026, from the phase 1/2 START-001 trial.
- The FDA granted Fast Track designation for invika in antigen-rich metastatic colorectal cancer and similar solid tumors.
Sources
This brief was written by Brightside Report from the reporting linked above. Spot an error? Request a correction.