Early-stage study shows novel immunotherapy may benefit patients with treatment-resistant solid tumours

Phase 1/2 findings published in Nature Medicine demonstrate how selectively activating T cells may offer a new approach to treating advanced cancers that no longer respond to existing therapies.

TORONTO, Oct. 23, 2026 /CNW/ -- A first-in-human clinical trial co-led by researchers at University Health Network's Princess Margaret Cancer Centre has found early signs that a novel immunotherapy may help some patients with advanced cancers that no longer respond to existing treatments.

The results of the international Phase 1/2 START-001 trial are published today in Nature Medicine. The study evaluated invikafusp alfa to establish its safety, biological activity and recommended dose for further study, while also providing early signals of anti-tumour activity in patients with advanced, treatment-resistant solid tumours, many of whom had stopped responding to previous immunotherapies.

Invikafusp alfa is an investigational, first-in-class, selective dual T cell agonist. It is a type of immunotherapy designed to activate two specific subsets of T cells, known as Vβ6 and Vβ10 T cells. These cells make up only about 10 per cent of all T cells but are commonly found within tumours and may play an important role in the immune system's ability to recognize and attack cancer.

Unlike immunotherapies that stimulate the immune system more broadly, invikafusp alfa is designed to selectively activate tumour-fighting T cells while limiting activation of other immune cells -- an approach intended to focus the immune response more precisely on cancer, potentially reducing unwanted side effects. Researchers observed selective expansion of these targeted T cells both in the bloodstream and inside tumours, providing early evidence that the therapy acted as intended.

"This study gives us early clinical evidence that selectively activating tumour-relevant T cells is possible and can produce anti-tumour activity," says Lillian Siu, Medical Oncologist, Senior Scientist at UHN's Princess Margaret Cancer Centre and a co-senior author of the study.

"These are early findings for a new class of immunotherapy, and they need to be confirmed in larger studies. What is encouraging is that we were able to establish a dose for further testing and see responses in a small number of patients with very advanced disease and limited treatment options," added Dr. Siu, who is also a Professor of Medicine at the University of Toronto.

Key findings

The study treated 58 participants at 10 cancer centres in Canada, France, Spain and the United States. The main analysis included 52 participants across 21 different types of advanced solid tumours. More than half had received four or more previous lines of therapy, and most had previously received immune checkpoint inhibitors, a common type of immunotherapy used to treat cancer.

Among the 27 participants treated at the doses selected for further study:

• 14.8 per cent experienced an objective response, meaning their tumours shrank enough to meet established clinical criteria for a response.
• 44.4 per cent experienced some degree of tumour shrinkage, even if the reduction was not large enough to qualify as an objective response.
• Among the 18 participants whose cancers had stopped responding to earlier immunotherapy, 66.7 per cent achieved disease control, meaning their cancer either shrank or remained stable.

Responses were observed in several tumour types, including microsatellite-stable colorectal cancer and non-small cell lung cancer with low PD-L1 expression. These cancers can be difficult to treat with currently available immunotherapies.

Limitations and future research

The Phase 1 portion of START-001 was designed primarily to evaluate safety and identify a dose for further study. The Phase 2 portion is designed primarily to measure early anti-tumour activity.

The findings presented here are based on a relatively small and diverse group of participants with different tumour types and treatment histories. Larger studies and longer follow-up will be needed to better understand which patients may benefit, how long responses may last and how the therapy compares with existing treatments.

The ongoing Phase 2 portion of START-001 continues to evaluate the therapy in additional patients.

Researchers are also exploring other potential applications for invikafusp alfa as part of broader efforts to better detect, monitor and intervene earlier in cancer recurrence. Supported by the Peter Gilgan Centre for Early Cancer Detection Research at UHN's Princess Margaret Cancer Centre, future research may investigate whether immunotherapies such as invikafusp alfa could have benefits earlier in the course of disease. 

The START-001 study was sponsored and funded by Marengo Therapeutics, developer of invikafusp alfa. The study was also supported in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health.

Dr. Lillian Siu serves as a scientific advisor to Marengo Therapeutics and holds equity in the company. UHN conducts clinical research supported by Marengo Therapeutics.

About Princess Margaret Cancer Centre

The Princess Margaret Cancer Centre, part of the University Health Network (UHN) and affiliated with the University of Toronto, is one of the top cancer centres in the world and the largest comprehensive cancer centre in Canada. Recognized globally for its excellence in cancer research, education, and patient care, The Princess Margaret is transforming the future of cancer through world-leading discoveries, clinical innovations, and a commitment to personalized care. Working in collaboration with The Princess Margaret Cancer Foundation and partners worldwide, the centre's scientists, clinicians, and trainees are advancing research, improving outcomes, and bringing hope to people affected by cancer everywhere. For more information, visit www.uhn.ca/PrincessMargaret 

About University Health Network

UHN is Canada's Hospital -- ranked #2 in the world, #1 in Canada. With 10 sites and more than 44,000 TeamUHN members, UHN consists of Toronto General Hospital, Toronto Western Hospital, Princess Margaret Cancer Centre, Toronto Rehabilitation Institute, The Michener Institute of Education and West Park Healthcare Centre. As Canada's top research hospital, the scope of biomedical research and complexity of cases at UHN have made it a national and international source for discovery, education and patient care. UHN has the largest hospital-based research program in Canada, with major research in neurosciences, cardiology, transplantation, oncology, surgical innovation, infectious diseases, genomic medicine and rehabilitation medicine. UHN is a research hospital affiliated with the University of Toronto. For more information, visit: www.uhn.ca  

SOURCE University Health Network

Media Contact: Ana Fernandes, Sr. Manager, External Communications, University Health Network, [email protected]