Cancer Research UK to support Aleta in bringing CAR-T cell therapy through clinical trials

Cancer Research UK is collaborating with the immune-oncology company Aleta to advance the company’s CAR-T therapy towards clinical trials.

Cancer Research UK will fund, sponsor and conduct the first-in-human Phase 1/2a clinical trial of Aleta’s CAR-T cell engager candidate, ALETA-001.

ALETA-001 is part of Aleta’s pipeline of therapies targeting blood cancers and solid tumours. It is being developed to treat people with B-cell lymphoma and leukaemia whose disease has progressed after receiving CD19 CAR-T cell therapy. If brought to market, ALETA-001 could offer another therapy for patients with limited treatment options.

CAR-T cell therapy sees T cells taken from a patient to be reprogrammed in a lab so they can recognise cancer cells and kill them. T cells taken from patients are engineered to carry a specific CD19 receptor on their surface, enabling them to target cancer cells and kill them through binding the CD19 antigen present on B cell leukaemia and lymphoma cells.

It’s thought that over half of patients treated with CD19 CAR-T cell therapy relapse due to a reduction or loss of CD19 expression. ALETA-001 works through binding to CD20 proteins present on the surface of cancer cells. This enables the therapy to reactivate CD19 CAR-T cells by ‘recoating’ the cancer cell with the target CD19 proteins and restoring the CAR-T cells ability to recognise and kill the cancer cell.

Paul Rennert, president, co-founder and chief scientific officer, Aleta Biotherapeutics, said: “We are deeply honoured to be partnering with Cancer Research UK to rapidly advance our lead drug candidate, ALETA-001, into the clinic. There is an urgent need to develop new therapies that can help people with B-cell cancers, such as lymphoma and leukaemia, whose cancer has progressed after treatment with CD19 CAR-T cell therapy. Our collaboration with Cancer Research UK is a strong endorsement of the potential of our scientific platform to address the critical issues of CAR-T cell persistence, tumour antigen loss leading to patient relapse, and tumour antigen heterogeneity. We look forward to working with Cancer Research UK’s exceptional network of experienced clinical trial investigators and researchers to conduct the trial.”

In this new trial, patients with B-cell lymphoma/leukaemia who have received CD19 CAR-T cell therapy but did not achieve a complete response or who relapsed from a complete response will be enrolled. After the recommended Phase 2 dose of ALETA-001 has been determined, Aleta will initiate a multi-center, single arm, pivotal Phase 2 trial in the United States focused on diffuse large B-cell lymphoma (DLBCL) patients. This clinical trial will be designed to support potential accelerated approval of ALETA-001.

Nigel Blackburn, Cancer Research UK’s director of Drug Development, said: “CAR-T cell therapy has been transformative in treating patients with hard-to-treat blood cancers, but many will see their cancer return and treatment options begin to run out. ALETA-001 uses a simple yet elegant method to redirect a patient’s circulating CD19 CAR-T cells against cancer cells expressing CD20, and we hope this could be a new treatment avenue for blood cancer.  This is a landmark collaboration for Cancer Research UK as it’s the first-in-human trial for a new drug that reboots CAR-T cell therapy, and we look forward to progress its early clinical development with Aleta.”