Tebentafusp is being developed as a first-of-its-kind immunotherapy drug that showed promise in clinical studies in helping the immune system fight off melanoma cancers of both the eye and skin
Immunotherapy is a mainstay of cancer treatment, helping the body use its own immune response to attack tumours. Thus far immunotherapy drugs have been used successfully in only some cancer types, such as cutaneous melanoma and lung cancer. These drugs (including checkpoint inhibitors) are less effective in patients whose tumour has fewer immune cells (particularly T cells) and lower mutational burden. This is thought to make it harder for the immune system to ‘see’ and target the tumour.
Metastatic uveal melanoma is one such type of cancer for which this is thought to be a problem, making it one of the deadliest cancers. However, a publication based on a collaboration between the University of Oxford and Immunocore has found that an investigational agent, tebentafusp, designed as a first-in-class bispecific fusion protein, shows the potential to treat both metastatic cutaneous melanoma (mCM, a skin cancer) and metastatic uveal melanoma (mUM, an eye cancer).
The study tested tebentafusp in humans for the first time, with 84 study participants with advanced melanoma receiving the drug. The drug takes a novel approach by redirecting immune T cells to kill tumours that express the gp100 antigen, which is commonly expressed on the cell surface of melanoma cells. They found that tebentafusp was well tolerated by patients, an important aspect of developing new drugs. It was also possible, through analysing patient samples, to show that the drug appeared to be successfully redirecting T cells to the tumour, as seen in tumour samples taken after treatment had started. The increase of immune pathway-related markers such as CXCL10 & CXCL11 appeared to be associated with patient survival, implying that the redirection of T-cells had a part to play in the anti-tumour response.
This suggests that tebentafusp has a potential as a treatment in melanomas of the skin or eye, and paves the way for further trials to confirm the effect on patient survival. Additional Immunocore molecules in development have the potential to treat other cancer indications, which are currently under investigation in a variety of advanced solid tumours.
Prof Mark Middleton, University of Oxford & study co-author said;
“This drug has had an interesting impact on patients with metastatic uveal melanomas, which has historically been very hard to treat. We hope that this approach of using T cells to infiltrate and attack the tumour will open up further opportunities for the treatment of cancers that have previously had limited treatment options”
Dr Koustubh Rande, Head of Translational Medicine at Immunocore commented;
“Identifying patients more likely to derive clinical benefit is a fundamental challenge facing immunotherapies. For this reason, we are pleased that a simple clinical biomarker—rash, which is easily recognisable by patients and physicians and was an on-target and off-tumour event of tebentafusp, may identify patients who are potentially more likely to benefit. These initial results will be evaluated in additional ongoing trials investigating the use of tebentafusp in uveal melanoma.”
About the research
This research was funded by Immunocore.
Prof Mark Middleton is the Head of the Department of Oncology at the University of Oxford. He has overseen the development of internationally leading melanoma and upper GI clinical research groups and establishment of portfolios of early phase radiotherapy and haematooncology trials in Oxford. He is involved in the evaluation of novel immunotherapeutics, including pre-clinical development, trial design, proof of mechanism and proof of concept.
Immunocore, is a pioneering, clinical-stage T cell receptor biotechnology company working to develop and commercialise a new generation of transformative medicines to address unmet needs in cancer, infection and autoimmune diseases. The Company’s most advanced programs are in oncology and it has a rich pipeline of programs in infectious and autoimmune diseases. Immunocore’s lead program, tebentafusp (IMCgp100), has entered pivotal clinical studies as a treatment for patients with metastatic uveal melanoma. Collaboration partners across the Immunocore pipeline include Genentech, GlaxoSmithKline, AstraZeneca, Eli Lilly and Company, and the Bill and Melinda Gates Foundation. Immunocore is headquartered at Milton Park, Oxfordshire, UK, with offices in Conshohocken, Pennsylvania and Rockville, Maryland in the US. For more information, please visit www.immunocore.com.