Immunocore announces randomization of first patient in the global, registrational Phase 3 clinical trial testing brenetafusp for the treatment of first-line advanced or metastatic cutaneous melanoma

The Phase 3 PRISM-MEL-301 trial will study the efficacy and safety of brenetafusp (IMC-F106C; PRAME-A02) in combination with nivolumab versus nivolumab or nivolumab + relatlimab in first-line advanced or metastatic cutaneous melanoma

First registrational Phase 3 trial investigating PRAME-targeted therapy

(OXFORDSHIRE, England & CONSHOHOCKEN, Penn. & ROCKVILLE, Md., US, 18 June 2024) Immunocore Holdings plc 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, today announces 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.

"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) 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.

About Immunocore

Immunocore is a commercial-stage biotechnology company pioneering the development of a novel class of TCR bispecific immunotherapies called ImmTAX – Immune mobilizing monoclonal TCRs Against X disease – designed to treat a broad range of diseases, including cancer, autoimmune, and infectious disease. Leveraging its proprietary, flexible, off-the-shelf ImmTAX platform, Immunocore is developing a deep pipeline in multiple therapeutic areas, including nine active clinical and pre-clinical programs in oncology, infectious diseases, and autoimmune diseases. The Company's most advanced oncology TCR therapeutic, KIMMTRAK 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.

Forward Looking Statements

This press release contains "forward-looking statements" within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "believe," "expect," "plan," "anticipate," "estimate," and similar expressions (as well as other words or expressions referencing future events or circumstances) are intended to identify forward-looking statements. All statements, other than statements of historical facts, included in this press release are forward-looking statements. These statements include, but are not limited to, statements regarding the expected clinical benefits of brenetafusp and the Company's expectations regarding the design, progress, randomization and scope of the Phase 3 PRISM-MEL301 trial with brenetafusp plus nivolumab versus standard nivolumab in 1L advanced cutaneous melanoma and the IMC-F106C-101 Phase 1/2 dose escalation trial with brenetafusp in patients with multiple solid tumor cancers including non-small cell lung cancer, small-cell lung cancer, endometrial, ovarian, cutaneous melanoma, and breast cancers. Any forward-looking statements are based on management's current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual events or results to differ materially and adversely from those set forth in or implied by such forward-looking statements, many of which are beyond the Company's control. These risks and uncertainties include, but are not limited to, the impact of worsening macroeconomic conditions on the Company's business, financial position, strategy and anticipated milestones, including Immunocore's ability to conduct ongoing and planned clinical trials; Immunocore's ability to obtain a clinical supply of current or future product candidates or commercial supply of KIMMTRAK or any future approved products, including as a result of health epidemics or pandemics, war in Ukraine, the conflict between Hamas and Israel, the broader risk of a regional conflict in the Middle East, or global geopolitical tension; Immunocore's ability to obtain and maintain regulatory approval of its product candidates, including KIMMTRAK; Immunocore's ability and plans in continuing to establish and expand a commercial infrastructure and to successfully launch, market and sell KIMMTRAK and any future approved products; Immunocore's ability to successfully expand the approved indications for KIMMTRAK or obtain marketing approval for KIMMTRAK in additional geographies in the future; the delay of any current or planned clinical trials, whether due to patient enrollment delays or otherwise; Immunocore's ability to successfully demonstrate the safety and efficacy of its product candidates and gain approval of its product candidates on a timely basis, if at all; competition with respect to market opportunities; unexpected safety or efficacy data observed during preclinical studies or clinical trials; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials or future regulatory approval; Immunocore's need for and ability to obtain additional funding, on favorable terms or at all, including as a result of worsening macroeconomic conditions, including inflation, interest rates and unfavorable general market conditions, and the impacts thereon of the war in Ukraine, the conflict between Hamas and Israel, and global geopolitical tension; Immunocore's ability to obtain, maintain and enforce intellectual property protection for KIMMTRAK or any of its product candidates it or its collaborators are developing; and the success of Immunocore's current and future collaborations, partnerships or licensing arrangements. These and other risks and uncertainties are described in greater detail in the section titled "Risk Factors" in Immunocore's filings with the Securities and Exchange Commission, including Immunocore's most recent Annual Report on Form 10-K for the year ended December 31, 2023 filed with the Securities and Exchange Commission on February 28, 2024, as well as discussions of potential risks, uncertainties, and other important factors in the Company's subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and the Company undertakes no duty to update this information, except as required by law.

Contact Information

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