On June 18, 2024 Immunocore Holdings plc (Nasdaq: IMCR) ("Immunocore" or the "Company"), a commercial-stage biotechnology company pioneering and delivering transformative immunomodulating medicines to radically improve outcomes for patients with cancer, infectious diseases and autoimmune diseases, reported randomization of the first patient in the PRISM-MEL-301 trial, assessing the efficacy and safety of brenetafusp (IMC-F106C; PRAME-A02), in combination with nivolumab, in first-line advanced or metastatic cutaneous melanoma (Press release, Immunocore, JUN 18, 2024, View Source [SID1234644424]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are very proud to have started the registrational program for brenetafusp, our PRAME candidate, supported by the recent promising brenetafusp monotherapy data in late-line cutaneous melanoma" said Mohammed Dar, Senior Vice President, Clinical Development, and Chief Medical Officer, Immunocore. "The PRISM-MEL-301 trial – the first Phase 3 trial for any PRAME-targeted therapy – will test whether combining brenetafusp with nivolumab may be a more effective treatment option than current standards of care for newly diagnosed metastatic or advanced cutaneous melanoma patients."

The Phase 3 trial (NCT06112314) will randomize HLA-A*02:01 positive patients with first-line, advanced or metastatic cutaneous melanoma to brenetafusp + nivolumab versus a control arm of either nivolumab or nivolumab + relatlimab, depending on country. Bristol Myers Squibb will provide nivolumab.

Professor Georgina Long, Co-Medical Director of Melanoma Institute Australia, said: "The PRISM-MEL-301 Phase 3 trial is a great example of outside-the-box scientific thinking, leveraging the immune system in a new way in the hope of beating cancer. My hope is that we can get closer to our goal of zero deaths from melanoma by conducting clinical trials with innovative drug therapies such as this."

The Company has shared the cutaneous melanoma Phase 1 data during an oral presentation at the 2024 American Society of Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on 31 May. The data showed that brenetafusp was well tolerated as monotherapy and in combination with anti-PD1, and demonstrated promising monotherapy clinical activity, including disease control rate (partial response and stable disease), progression free survival, and circulating tumor DNA molecular response.

Brenetafusp is the first PRAME x CD3 ImmTAC bispecific protein targeting an HLA-A*02:01 PRAME (PReferentially expressed Antigen in Melanoma) antigen. The Company is continuing to enroll patients into a Phase 1/2 trial in monotherapy and combination arms across multiple tumor types, including three expansion arms for patients with advanced ovarian, non-small cell lung, and endometrial cancers.

About ImmTAC molecules for cancer

Immunocore’s proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules that are designed to redirect the immune system to recognize and kill cancerous cells. ImmTAC molecules are soluble TCRs engineered to recognize intracellular cancer antigens with ultra-high affinity and selectively kill these cancer cells via an anti-CD3 immune-activating effector function. Based on the demonstrated mechanism of T cell infiltration into human tumors, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumors, regardless of mutational burden or immune infiltration, including immune "cold" low mutation rate tumors.

About PRISM-MEL-301 – Phase 3 trial with brenetafusp (IMC-F106C, PRAME-A02) in 1L advanced cutaneous melanoma

The Phase 3 registrational trial will randomize HLA-A*02:01-positive patients with previously untreated advanced melanoma to brenetafusp + nivolumab versus nivolumab or nivolumab + relatlimab, depending on the country where the patient is enrolled. The trial will initially randomize to three arms: two brenetafusp dose regimens (40 mcg and 160 mcg) and control arm and will discontinue one of the brenetafusp dose regimens after an initial review of the first 60 patients randomized to the two experimental arms (90 patients randomized total). The primary endpoint of the trial is progression free survival (PFS) by blinded independent central review (BICR), with secondary endpoints of overall survival (OS) and overall response rate (ORR).

About the IMC-F106C-101 Phase 1/2 trial

IMC-F106C-101 is a first-in-human, Phase 1/2 dose escalation trial in patients with multiple solid tumor cancers including non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), endometrial, ovarian, cutaneous melanoma, and breast cancers. The Phase 1 dose escalation trial was designed to determine the maximum tolerated dose (MTD), as well as to evaluate the safety, preliminary anti-tumor activity and pharmacokinetics of IMC-F106C (brenetafusp), a bispecific protein built on Immunocore’s ImmTAC technology, and the Company’s first molecule to target the PRAME antigen. The Company has initiated patient enrollment into four expansion arms in cutaneous melanoma, ovarian, NSCLC, and endometrial carcinomas. The IMC-F106C-101 trial is adaptive and includes the option for Phase 2 expansion, allowing for approximately 100 patients treated per tumor type in the Phase 1 and 2 expansion arms. Ph1 monotherapy continues in additional solid tumors as well as multiple combinations with standards-of-care, including checkpoint inhibitors, chemotherapy, targeted therapies, and tebentafusp.

About Cutaneous Melanoma

Cutaneous melanoma (CM) is the most common form of melanoma. It is the most aggressive skin carcinoma and is associated with the vast majority of skin cancer-related mortality. The majority of patients with CM are diagnosed before metastasis but survival remains poor for the large proportion of patients with metastatic disease. Despite recent progress in advanced melanoma therapy, there is still an unmet need for new therapies that improve first-line response rates and duration of response as well as for patients who are refractory to first-line treatments.