Novel cancer immunotherapy drug generates promising clinical trial results
Mass General Brigham Cancer Institute researchers co-led the first-in-human trial of invikafusp, which selectively activates immune cells and delivers a potent immunotherapy molecule.
Cancer immunotherapy medications, which boost the body’s immune response to fight cancer cells, have improved patient survival across several tumor types, but only a minority of patients derive long-term benefits, with cancers often developing resistance to treatment. Early-phase clinical trials co-led by researchers from the Mass General Brigham Cancer Institute demonstrate the potential of a novel immunotherapy drug — invikafusp — that is continuing to be evaluated as a precision immunotherapy for patients with metastatic tumors that are resistant to therapies. The findings are published in Nature Medicine and simultaneously presented at the ESMO Congress 2026.
“There have been many attempts to extend the promise of immunotherapy to more patients. The development of invikafusp was launched in this spirit,” said co–lead author Ryan J. Sullivan, MD, a physician-scientist with the Mass General Brigham Cancer Institute. “When we saw the initial data from laboratory experiments, there was a lot of excitement about the promise of this therapy.”
In addition to lacking long-term potency, current immunotherapy agents can cause indiscriminate stimulation of T cells and other immune response mediators, which can lead to serious side effects. A more selective medication may address these shortcomings. Sullivan and his colleagues evaluated invikafusp, which binds to two receptors on Vβ6/Vβ10 T cells that are known to infiltrate tumors and are associated with anti-tumor activity. Upon cooperatively binding to these two receptors (the T-cell receptor and the interleukin-2 receptor), invikafusp promotes the expansion of these particular T cells without affecting other immune cells.
The START-001 trial was sponsored by Marengo Therapeutics, which is developing invikafusp. As part of the trial, the researchers tested invikafusp in 34 patients who had advanced solid tumors and few remaining treatment options in a dose-escalating phase 1 clinical trial, which showed that the drug was well-tolerated. Subsequently, 18 patients were enrolled in a phase 2 trial. Treatment-related side effects in this trial were mostly mild to moderate. Disease control rates (when tumors shrink or remain stable) were 59.3% at the optimal doses of invikafusp, with meaningful tumor shrinkage in 15% of patients. Invikafusp selectively and potently expanded circulating and intratumoral Vβ6/Vβ10 T cells, peaking at the optimal doses.
“There are certainly more studies to complete to understand which patients should be treated with invikafusp, but the initial findings support the continued study of this promising drug,” said Sullivan.
Read the paper
Invikafusp alfa, a first-in-class bispecific dual T-cell agonist, in immune checkpoint blockade-resistant, antigen-rich solid tumors
Authorship: In addition to Ryan J. Sullivan, co-first authors of the study were Nicholas P. Tschernia of the National Cancer Institute and Claire F. Friedman of Memorial Sloan Kettering Cancer Center. Lillian L. Siu of Princess Margaret Cancer Centre and James L. Gulley of the National Cancer Institute were co-senior authors. A complete list of authors is available in the paper.
Disclosures: Several study authors are employees of Marengo Therapeutics. Sullivan has received institutional research funding from BioNTech SE, Bristol Myers Squibb, Genentech/Roche, Georgiamune, Immunocore, Marengo Therapeutics, Merck, Moderna, Novartis, Pfizer, Relay, SpringWorks Therapeutics and Synthekine, and has served as a consultant or advisory board member for Marengo Therapeutics, Merck, Novartis, Pfizer, PharmaMar and Replimune. Additional author disclosures can be found in the paper.
Funding: This study was funded in part by Marengo Therapeutics and the National Institutes of Health’s Intramural Research Program of the National Cancer Institute’s Center for Cancer Research (ZIA BC 010666). Marengo Therapeutics also supported medical writing assistance provided by Kathleen M. Ohleth and Pamela Harvey of Acumen Medical Communications.
Paper cited: Sullivan RJ, et al. “Invikafusp alfa, a first-in-class bispecific dual T-cell agonist, in immune checkpoint blockade-resistant, antigen-rich solid tumors: results from the phase 1/2 START-001 trial.” Nature Medicine DOI: 10.1038/s41591-026-04711-0
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