Immunocore Holdings PLC (NASDAQ: IMCR) has presented phase 1 data on Brenetafusp, an IMTAC bispecific targeting PRAME, in patients with platinum-resistant ovarian cancer at the 2024 European Society for Medical Oncology (ESMO) Congress.
In the phase 1 monotherapy data, 37 heavily pre-treated (median 5 prior lines) serous ovarian cancer patients were treated with Brenetafusp. 81% had received prior bevacizumab, and 59% had received prior PARP inhibitors. Brenetafusp was well tolerated, with reversible and manageable cytokine release syndrome observed in 57% of patients. Of the 31 patients evaluable for tumor assessment, 58% demonstrated disease control, including two confirmed partial responses, with a median progression-free survival (PFS) of 3.3 months and an overall survival (OS) of 73% at 6 months. Additionally, 31% of patients had a molecular response (≥0.5 log reduction by week 9) in circulating tumor DNA (ctDNA), and patients with a baseline blood T cell fitness (TCF) gene expression signature above median showed greater activity, including disease control (80% vs. 38%) and PFS (3.7 months vs. 2.2 months).
In the phase 1 chemotherapy combination data, 16 patients with platinum-resistant ovarian cancer were treated with Brenetafusp and either gemcitabine, nab-paclitaxel, or pegylated doxorubicin chemotherapy. All 13 patients evaluated for tumor assessment achieved disease control, including three partial responses, and the molecular response rate was 82%.
The company also presented translational data showing that the T cell fitness gene expression signature in blood is an important parameter associated with clinical activity for both Kimmtrak (tebentafusp-tebn) and Brenetafusp in metastatic uveal melanoma. Patients with a TCF signature above median had higher clinical activity, including longer OS (28 months vs. 11 months) and PFS (5 months vs. 2 months).
Immunocore's proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called IMTAC (immune mobilizing monoclonal TCRs against cancer) molecules, designed to redirect the immune system to recognize and kill cancerous cells. Brenetafusp, a bispecific protein built on Immunocore’s IMTAC technology, targets the PRAME antigen.
The phase 1 trial, known as IMC-F106C-101, is a first-in-human, dose escalation trial in patients with multiple solid tumor cancers, including ovarian cancer. The trial is adaptive and includes the option for phase 2 expansion, allowing for approximately 100 patients to be treated per tumor type in the phase 1 and 2 expansion arms.
Ovarian cancer is diagnosed at an advanced stage in most patients, and there is a significant unmet need for new therapies that improve clinical outcomes in both platinum-sensitive and platinum-resistant ovarian cancer patients. Uveal melanoma, on the other hand, is a rare and aggressive form of melanoma affecting the eye, with up to 50% of patients developing metastatic disease.
Kimmtrak, a novel bispecific protein targeting gp100, has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in the United States, European Union, Canada, Australia, and the United Kingdom.
The most common adverse reactions in patients who received Kimmtrak were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. Today the company's shares have moved 1.6% to a price of $33.55. Check out the company's full 8-K submission here.
