Early NIH-Led Trial Finds T-Cell Drug Invika Stalls Resistant Tumours

An experimental drug that switches on a narrow group of immune cells stopped cancer from progressing in 16 of 27 patients who received the optimal dose, in an early trial led by researchers at the US National Institutes of Health. The drug, invikafusp alfa, or invika, was tested in people whose solid tumours had mostly stopped responding to standard immunotherapy. In four of the 27, tumours shrank by more than 30%.

The results come from the phase 1/2 START-001 trial and were published in Nature Medicine on 23 October. In a news release the same day, NIH said the study was led by researchers at its National Cancer Institute (NCI), Mass General Brigham and Memorial Sloan Kettering. The researchers themselves describe the findings as early.

How invika works

Many cancer immunotherapies work by releasing the brakes on the immune system. Drugs known as immune checkpoint blockers, such as pembrolizumab, have changed treatment for several cancers. But NIH notes that many patients benefit for only a short time, or not at all, and that other approaches that rally T cells usually do so “indiscriminately”, often causing severe side effects.

Invika is designed to be more selective. The paper describes it as a “first-in-class, bispecific, dual T cell agonistic antibody” that targets two subsets of T cells, known as Vβ6 and Vβ10. By activating only this narrow population, NIH says, the drug aims to drive an attack on tumours while avoiding the harm that broader stimulation can cause. The study found that the drug expanded the target T cells without affecting other T cells.

What the trial found

In phase 1, participants with a wide range of cancers received different doses every two weeks, so the team could check safety and find the best dose. Phase 2 then treated people at that dose.

Of the 27 participants treated at the optimal dose across both phases, NIH says, disease did not progress in 16 (59.3%). Four (14.8%) saw targeted tumours shrink by more than 30%. Two of the four had metastatic colorectal cancer of a type NIH calls “notoriously treatment-resistant” and were on invika as their seventh line of therapy. A third had stage 4 non-small cell lung cancer that had resisted several treatments, including checkpoint blockers. At lower doses, the paper reports no tumour responses, and NIH says invika “did not appear to have significant benefit”.

On safety, several participants had flu-like side effects, which NIH says were “expected and generally manageable”. The paper reports that the most common treatment-related side effect was cytokine release syndrome, an immune overreaction, mainly at the two mildest grades. Two participants had dose-limiting side effects that reversed, and there were no treatment-related deaths.

“Patients whose tumors are advanced — particularly tumors that don’t respond well to immunotherapy — often have their backs against a wall,” said James Gulley, clinical director at NCI’s Center for Cancer Research and a co-corresponding author.

Why “did not progress” is not the same as shrinking

The headline number needs care. Sixteen of 27 means that, according to NIH, the disease did not advance in those patients. It does not mean tumours went away, and only four of the 27 had the kind of shrinkage counted as a response. Neither the release nor the paper’s abstract gives figures on how long that control lasted or on survival, which is what patients and regulators will ultimately judge the drug on.

The trial is also small, and every participant received invika, so there is no comparison group showing how similar patients would have done on other treatment. Phase 1 was built to test safety and choose a dose. The paper describes the anti-tumour results as “preliminary evidence” and says the phase 2 study is continuing. The trial was sponsored by the drug’s developer, Marengo Therapeutics, which the paper says designed and analysed the study, and NIH has a research agreement with the company.

The researchers are careful about this too. “These results are early, and although signs of immune activity don’t always translate into benefit to patients at this stage, it is new and exciting to see activity in patients whose cancers had stopped responding to immunotherapy — a group of people with very few options left,” said co-first author Nicholas Tschernia of NCI. The study linked the four cases of tumour shrinkage to the largest changes in the target T cells, but found that immune activity alone did not always produce a measurable response.

That fits a busy week for cancer immunotherapy. TSN reported on a personalised mRNA treatment that cut melanoma recurrence in a large phase 3 trial, a much later stage of testing than START-001. It also covered an AI tool that spots a DNA-repair defect in ovarian cancer.

The trial is still recruiting

The US Food and Drug Administration has given invika Fast Track designation for antigen-rich metastatic colorectal cancer, and more recently for similar solid tumours of any tissue type after checkpoint inhibitor treatment. Tschernia says the findings give the team reason to keep studying invika, particularly in combination with other cancer treatments. NIH says the trial (NCT05592626) is still seeking participants.

TSN collects medical and scientific advances on its Tech for Good hub and in its weekly Tech for Good roundup.

Related: KRAS Pancreatic Cancer Vaccine Misses Main Goal but Primes T Cells.

Sources

• National Institutes of Health, “A precision T-cell therapy stalls treatment-resistant cancers in clinical trial”, 23 October 2026
• Sullivan, R. J., Tschernia, N. P., Friedman, C. F. et al., “Bispecific dual T cell agonist invikafusp alfa in solid tumors: the phase 1/2 START-001 trial”, Nature Medicine, 23 October 2026
• ClinicalTrials.gov, NCT05592626 (START-001)

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