A New Immunotherapy Approach
Early trial shows that new drug has anti-tumour activity in patients with advanced cancer.
Despite the impact immunotherapy has had on cancer treatment, there is a need for new immunotherapies that have longer lasting effects with fewer side effects. The investigational drug, invikafusp alfa, uses a new and unique mechanism of action to treat cancer, targeting specific subsets of T cells to improve specificity.
A study published in Nature Medicine from UHN’s Princess Margaret Cancer Centre and collaborators found that a first-of-its-kind, investigational immunotherapy drug, invikafusp alfa (invika), showed early signs of anti-tumour activity in people with various types of advanced and treatment-resistant forms of cancer.
Cancer immunotherapy, which helps the immune system recognize and attack cancer cells, has transformed cancer treatment by improving outcomes for many types of cancer. One type of therapy, called immune checkpoint blockade (ICB), blocks checkpoint proteins that normally act as “brakes” on the immune system and prevent immune responses from becoming too strong. Some cancers exploit these checkpoint proteins to switch off cancer-fighting immune cells known as T cells. Blocking the checkpoints can help T cells remain active and attack the cancer.
Despite immense research in this area, only some patients achieve long-term benefits from ICB and there is a high likelihood of developing drug resistance. In addition, these treatments can trigger non-specific components of the immune system, which can lead to serious side effects.
There is a need for new immunotherapies that can generate strong and durable responses. As a result, a new generation of immunotherapies is being designed to be more selective. One such medication is invika, developed to both selectively bind to and activate Vβ6/Vβ10 T cell subsets—T cells that carry specific receptors on their surface. This specificity aims to enhance the tumour-specific immune response and improve safety.
In an early-phase clinical trial, the first trial of this drug in patients, participants with advanced solid tumours that had resistance to other therapies, including ICB, were treated with invika. The trial was designed to evaluate the safety of invika and identify a dose for further study (the recommended phase 2 dose), as well as measure preliminary anti-tumour activity. The study included 58 participants at hospitals around the world, including UHN’s Princess Margaret Cancer Centre.
Results showed that the drug was well-tolerated with an acceptable safety profile. Among the 27 participants treated at the recommended phase 2 dose, 14.8 % showed a response where tumours shrank enough to meet established clinical criteria. There was also some degree of tumour shrinkage in 44% of patients, even when the reduction was not large enough to meet the official criteria. These responses were observed in many tumour types such as cervical cancer, pancreatic cancer, melanoma, and more.
In 18 participants who had cancers that had stopped responding to earlier immunotherapy, and received invika at the recommended phase 2 dose, 66.7% achieved disease control, meaning their cancer either shrank or remained stable. Researchers also observed expansion of targeted T cells both in the bloodstream and inside tumours, providing early evidence that the therapy acted as intended.
Overall, these findings provide preliminary evidence of anti-tumour activity and support further study of invika in people with advanced cancers. Larger trials are needed to determine how well the drug works, which patients are most likely to benefit and how its risks compare with its potential benefits.
Dr. Ryan Sullivan from Mass General Research Institute and Harvard Medical School; Nicholas Tschernia, from the National Cancer Institute; and Claire Friedman from Memorial Sloan Kettering Cancer Center, at the time of this research, are co-first authors of the study.
Dr. Ke Liu from Marengo Therapeutics and Dr. James Gulley from the National Cancer Institute are co-corresponding authors of the study.
Dr. Lillian Siu, Senior Scientist and Medical Oncologist at UHN’s Princess Margaret Cancer Centre and Professor in the Department of Medicine at the University of Toronto, is the Co-Corresponding author of the study.
The START-001 phase 1/2 trial was supported by Marengo Therapeutics. This work was supported in part by the Center for Cancer Research, NCI, NIH and The Princess Margaret Cancer Foundation.
Dr. Lillian Siu is a consultant/advisory board member for Merck, Roche, Voronoi, GSK, Bayer, Pfizer, Arvinas, Daiichi Sankyo, Amgen, Pangea, Tubulis, LTZ Therapeutics, Marengo, AstraZeneca, Incyte, Gilead, Bristol-Myers Squibb, Systinn, Systimmune, EMD Serono, and MBrace. She reports other competing interests that can be found in the manuscript.
For a full list of competing interests, see the manuscript.
Sullivan RJ, Tschernia NP, Friedman CF, Herrera M, Sonpavde GP, He K, Italiano A, Marabelle A, Roulleaux-Dugage M, Danlos FX, Cabanas EG, Hernando-Calvo A, Pedregal M, Parikh A, Iyer G, Zakari A, Wherry EJ, Schlom J, Donahue RN, McCue S, Cross S, Srinivasan K, Benincosa L, Katragadda M, Shun Z, Chin K, Su Z, Liu K, Siu LL, Gulley JL. Bispecific dual T cell agonist invikafusp alfa in solid tumors: the phase 1/2 START-001 trial. Nat Med. 2026 Oct 23. doi: 10.1038/s41591-026-04711-0. Epub ahead of print.