Immunocore's Phase 1 Data on Brenetafusp for Ovarian Cancer

Immunocore Holdings plc, a biotechnology company focused on developing innovative immunotherapies, recently presented Phase 1 data on brenetafusp, a bispecific ImmTAC targeting PRAME, in patients with platinum-resistant ovarian cancer at the 2024 European Society for Medical Oncology (ESMO) Congress. The data from this trial show that brenetafusp is clinically active both as a monotherapy and in combination with chemotherapy in patients who have been heavily pre-treated.

Brenetafusp demonstrated encouraging signs of clinical activity, such as disease control, ctDNA molecular response, and an association with T cell fitness. David Berman, Head of Research and Development at Immunocore, noted the significance of these results, especially for patients who have undergone multiple lines of prior treatment. He emphasized the potential for brenetafusp to be effective in treating ovarian cancer, both alone and alongside chemotherapy.

Dr. Claire Friedman from Memorial Sloan Kettering Cancer Center highlighted the challenges in treating recurrent ovarian cancer and expressed optimism that brenetafusp could offer new treatment options for patients with advanced, platinum-resistant ovarian cancer.

In the clinical trial, 37 patients with serous ovarian cancer, who had undergone a median of five prior treatment lines, received brenetafusp monotherapy. The majority of these patients had previously been treated with bevacizumab and PARP inhibitors. The results showed that brenetafusp was well tolerated, with the most common adverse event being a manageable cytokine release syndrome observed in 57% of patients.

Among the 31 evaluable patients for tumor assessment, 58% demonstrated disease control, including two confirmed partial responses. Despite tumor progression in some patients, 64% continued treatment beyond progression for a median of two additional months. The median progression-free survival (PFS) was 3.3 months, and the six-month overall survival (OS) rate was 73%.

Additionally, the trial revealed a correlation between T cell fitness (TCF) gene expression in blood and clinical activity. Patients with a higher TCF signature showed greater disease control, longer PFS, and a higher six-month OS rate. This finding was consistent across different types of tumors, suggesting the broader applicability of the TCF signature as a marker for brenetafusp's clinical activity.

In combination with chemotherapy, brenetafusp was administered to 16 patients with platinum-resistant ovarian cancer. These patients had previously received a median of four treatment lines, including bevacizumab and PARP inhibitors. The combination therapy showed a safety profile consistent with expectations for the individual agents. Of the 13 evaluable patients for tumor assessment, 69% achieved disease control, including three partial responses, which is a significant improvement over historical chemotherapy efficacy data for this patient population.

Furthermore, the molecular response rate in ctDNA for patients receiving the combination therapy was notably high at 82%. This response was associated with longer OS and PFS, aligning with previous findings for brenetafusp in cutaneous melanoma.

Immunocore's proprietary T cell receptor (TCR) technology underpins the development of brenetafusp and other ImmTAC molecules. These bispecific biologics are engineered to target intracellular cancer antigens with high affinity and selectively kill cancerous cells. The ongoing IMC-F106C-101 trial is a first-in-human Phase 1/2 study designed to evaluate the safety, preliminary anti-tumor activity, and pharmacokinetics of brenetafusp across several solid tumor types, including ovarian cancer.

Ovarian cancer remains a challenging disease with high mortality rates due to its advanced stage at diagnosis and resistance to conventional platinum-based chemotherapy. Brenetafusp's promising early data suggest it may address the significant unmet need for more effective treatments in both platinum-sensitive and platinum-resistant ovarian cancer patients.

The development of KIMMTRAK, another product from Immunocore, has already shown success in treating metastatic uveal melanoma, a rare and aggressive eye cancer. This bispecific protein targets the gp100 antigen and activates T cells to kill tumor cells, marking a significant advancement in immunotherapy for this condition.

Overall, Immunocore's innovative approach to TCR-based therapies continues to show potential in improving outcomes for patients with various types of cancer, including those with few other treatment options.