Experimental T-cell drug invika stalled tumor growth in 16 of 27 patients at optimal dose

The National Institutes of Health on Friday, October 23, 2026, reported early results from the first trial of the experimental drug invikafusp alfa, known as invika, in humans. At the optimal dose, disease did not progress in 16 of 27 treated participants with solid tumors, most of which had not responded well to standard immunotherapy ^[1].

The phase 1/2 study, called START-001, was published in Nature Medicine the same day, according to the NIH release. Researchers at NIH, Mass General Brigham and Memorial Sloan Kettering led the work. Marengo Therapeutics is the treatment sponsor ^[1].

Among those 27 participants, four had targeted tumors shrink by more than 30%, the release said. NIH described the drug as well tolerated at optimal doses ^[1].

What the records show

Invika is a protein built to engage a small subset of T cells: two groups of tumor-infiltrating lymphocytes, according to NIH. The aim of activating only that narrow population, rather than T cells in general, is anti-tumor activity without the severe side effects that less selective approaches can cause ^[1].

The trial enrolled patients with a wide variety of cancers. Most had not responded well to immune checkpoint blockade (ICB) ^[1].

• Phase 1: Participants received varying doses of invika every two weeks so researchers could evaluate safety and find the optimal dose. That dose was defined as the lowest one at which the desired effects peaked ^[1].
• Phase 2: Participants were treated at the optimal dose ^[1].
• Disease control: Across both phases, disease did not progress in 16 (59.3%) of the 27 participants given the optimal dose ^[1].
• Tumor shrinkage: Four (14.8%) had decreases of more than 30% in the size of targeted tumors ^[1].
• Responders: Two of the four had metastatic colorectal cancer with tumors of a type NIH called "notoriously treatment-resistant," and both were receiving invika as seventh-line therapy. Another had stage 4 non-small cell lung cancer whose tumors had failed several prior therapies, ICB among them ^[1].
• Lower or non-optimal doses: In those participants, invika "did not appear to have significant benefit," according to the release ^[1].

On safety, the release said several participants had flu-like side effects. NIH described these as expected and generally manageable with additional medication and supportive care ^[1].

The authors found the drug expanded the target T-cell populations without affecting any other T cells, per NIH. They tied the four cases of tumor reduction to the largest changes in those populations. Immune activity by itself did not always lead to a measurable clinical response, which the authors had expected at this early stage ^[1].

Why it matters for clinicians

NIH said many patients benefit from immunotherapies only briefly or not at all. Tumors often adapt to ICB drugs such as pembrolizumab, which limits long-term benefit. Other strategies to rally T cells usually act indiscriminately and commonly cause severe side effects, according to the release ^[1].

The trial focused on that group of patients whose cancers had stopped responding. "Patients whose tumors are advanced — particularly tumors that don’t respond well to immunotherapy — often have their backs against a wall," said co-corresponding author James Gulley, M.D., Ph.D., clinical director at the Center for Cancer Research (CCR) in NIH's National Cancer Institute (NCI) ^[1].

Co-first author Nicholas Tschernia, M.D., a physician-scientist early investigator in the CCR at NCI, urged caution. "These results are early," he said, adding that the activity appeared in "a group of people with very few options left" ^[1].

Context

Preclinical studies, also done at CCR, indicated that invika hits its intended targets and drives anti-tumor activity in animal models, NIH said ^[1].

Marengo Therapeutics had previously announced that the U.S. Food and Drug Administration granted invika Fast Track designation for antigen-rich, metastatic colorectal cancer. The FDA has since granted the same designation for similar solid tumors of any tissue type after prior therapy that included checkpoint inhibitors, according to the release ^[1].

What the records do not tell us

• The release does not give the total number of participants enrolled at all dose levels, or the optimal dose itself.
• It does not report rates of serious adverse events, treatment discontinuations or deaths.
• It does not say how long disease control or tumor shrinkage lasted, and it reports no survival data.
• It does not list every cancer type enrolled or describe a comparison or control group.
• It does not give dates for the Fast Track designations. Fast Track is not an approval, and the release calls invika experimental.
• This report is based on the NIH release; the full Nature Medicine paper was not part of the records reviewed.
• No comment from Marengo Therapeutics appears in the records.

What to watch

NIH said the trial is ongoing and still seeking participants through NCI. Tschernia said the findings support further study of this type of immunotherapy, particularly in combination with other cancer treatments ^[1].

This is news, not medical advice. EMS clinicians: follow your local protocols and medical direction.