Immunocore receives positive CHMP opinion for KIMMTRAK® (tebentafusp) for the treatment of unresectable or metastatic uveal melanoma

Rhea-AI Summary

Immunocore announced a positive opinion from the CHMP recommending approval of KIMMTRAK® (tebentafusp) for treating unresectable or metastatic uveal melanoma (mUM) in Europe. If sanctioned by the EMA, KIMMTRAK would be the first approved therapy in this indication. The treatment showed significant overall survival benefits in clinical trials, with a hazard ratio of 0.51. KIMMTRAK has already received FDA approval in the U.S. Offering a new hope for patients, this therapy is part of Immunocore’s innovative T cell receptor treatment platform.

Positive

• KIMMTRAK received a positive CHMP opinion for mUM treatment, moving closer to EMA approval.
• The therapy demonstrated a statistically significant overall survival benefit with a hazard ratio of 0.51.
• KIMMTRAK would be the first approved treatment for mUM in Europe, filling an urgent medical need.

Negative

• None.

PRESS RELEASE

Immunocore receives positive CHMP opinion for KIMMTRAK® (tebentafusp) for the treatment of unresectable or metastatic uveal melanoma

If approved by the European Medicines Agency, KIMMTRAK will be the first and only treatment option approved in Europe to treat patients with unresectable or metastatic uveal melanoma

KIMMTRAK demonstrated statistically and clinically meaningful overall survival (OS) benefit, hazard ratio of 0.51, with median OS of almost 22 months

(OXFORDSHIRE, England & CONSHOHOCKEN, Penn. & ROCKVILLE, Md., US, 25 February 2022) Immunocore Holdings plc (Nasdaq: IMCR) (“Immunocore” or the “Company”), a commercial-stage biotechnology company pioneering the development of a novel class of T cell receptor (TCR) bispecific immunotherapies designed to treat a broad range of diseases, including cancer, autoimmune and infectious diseases today announces that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending the approval of KIMMTRAK® (tebentafusp) for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM).

The CHMP positive opinion is one of the final steps before marketing authorization is granted by the EMA, which has the authority to approve medicines for use throughout the European Union. If approved, KIMMTRAK® would be the first T cell receptor therapy commercially available in Europe. Immunocore’s Marketing Authorisation Application was reviewed under EMA’s accelerated assessment procedure, which is given if the CHMP determines the treatment is of major interest from a public health perspective and represents a therapeutic innovation.

“The CHMP’s recommendation of KIMMTRAK brings us closer to providing a much-needed treatment option to patients in Europe,” said Bahija Jallal, Chief Executive Officer of Immunocore. “This year, hundreds of people across the EU will be diagnosed with metastatic uveal melanoma. Left with minimal-to-no options, these patients have a devastating prognosis. KIMMTRAK is the first therapy to demonstrate a survival benefit in patients with this disease, providing new hope to these individuals and to the doctors treating them.”

The recommendation comes just one month after regulatory approval of KIMMTRAK by the United States Food and Drug Administration (FDA) last month (January 25), making it the first and now only therapy for the treatment of unresectable or metastatic uveal melanoma to be approved by the FDA.
The CHMP recommendation of KIMMTRAK is based on the results of Immunocore’s Phase 3 IMCgp100-202 clinical trial, which were published in the September 23, 2021 issue of the New England Journal of Medicine. The randomized pivotal trial evaluated overall survival (OS) of KIMMTRAK compared to investigator’s choice (either pembrolizumab, ipilimumab, or dacarbazine) in patients with previously untreated mUM. 378 patients were randomized in a 2:1 ratio to either KIMMTRAK or investigator’s choice. Data from the trial, the largest Phase 3 trial undertaken in mUM, showed that KIMMTRAK demonstrated unprecedented median OS benefit as a first-line treatment. The OS Hazard Ratio (HR) in the intent-to-treat population favored KIMMTRAK, HR=0.51 (95% CI: 0.37, 0.71); p< 0.0001, over investigator’s choice (82% pembrolizumab; 13% ipilimumab; 6% dacarbazine). In the clinical trials, across both arms, patients stopped treatment for disease progression, unless the patient was otherwise deriving benefit, or for unacceptable toxicity.¹
Dr. Paul Nathan, uveal melanoma lead for the European Organisation for Research and Treatment of Cancer, said: “Metastatic uveal melanoma has historically been associated with a particularly poor prognosis and, up until now, has been refractory to most treatments. KIMMTRAK represents a significant new form of treatment, offering the chance at a longer life for patients with the disease, and with it, hope.”

In the randomised Phase 3 trial of KIMMTRAK (tebentafusp), treatment-related adverse reactions were manageable and consistent with the proposed mechanism of action. Among the patients treated with KIMMTRAK, the most common Grade 3 or higher adverse events were rash (18%), pyrexia (4%), and pruritus (5%). In the 245 patients treated with KIMMTRAK, Grade 3 cytokine release syndrome (CRS) occurred in <1% of patients and were generally well-managed. There were no Grade 4 CRS events observed in the Phase 3 clinical trial.

The United Kingdom’s Medicines and Healthcare Regulatory Agency (MHRA), Health Canada, and the Australian Government Department of Health Therapeutic Goods Administration (TGA) have each accepted the submission of the Company’s Marketing Authorisation Application. In April of 2021, Immunocore launched a global early access program to make KIMMTRAK readily available to mUM patients. The Company is focused on continuing to treat these patients with KIMMTRAK as regulatory approval is sought in the EU and the individual EU Member States. There are currently over 200 patients in the early access program.

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About Uveal Melanoma
Uveal melanoma is a rare and aggressive form of melanoma, which affects the eye. Although it is the most common primary intraocular malignancy in adults, the diagnosis is rare, and up to 50% of people with uveal melanoma will eventually develop metastatic disease. Unresectable or metastatic uveal melanoma typically has a poor prognosis and had no approved treatment until KIMMTRAK.

About KIMMTRAK®
KIMMTRAK is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. KIMMTRAK specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma. This is the first molecule developed using Immunocore’s ImmTAC technology platform designed to redirect and activate T cells to recognize and kill tumor cells. KIMMTRAK has been granted Breakthrough Therapy Designation, Fast Track designation and orphan drug designation by the FDA in the United States, Accelerated Assessment by the EMA, and Promising Innovative Medicine (PIM) designation under the UK Early Access to Medicines Scheme for metastatic uveal melanoma.

About Phase 3 IMCgp100-202 Trial
The IMCgp100-202 (NCT03070392) is a randomized pivotal trial that evaluated overall survival (OS) of KIMMTRAK (tebentafusp-tebn) compared to investigator’s choice (either pembrolizumab, ipilimumab, or dacarbazine) in HLA-A*02:01-positive adult patients with previously untreated mUM. KIMMTRAK demonstrated an unprecedented OS benefit with a Hazard Ratio (HR) in the intent-to-treat population favoring KIMMTRAK, HR=0.51 (95% CI: 0.37, 0.71); p< 0.0001, over investigator’s choice (82% pembrolizumab; 13% ipilimumab; 6% dacarbazine).

IMPORTANT U.S. SAFETY INFORMATION Regarding FDA Approval

Cytokine Release Syndrome (CRS), which may be serious or life-threatening, occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours following first three infusions and then as clinically indicated. Manifestations of CRS may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache. CRS occurred in 89% of patients who received KIMMTRAK with 0.8% being grade 3 or 4. Ensure immediate access to medications and resuscitative equipment to manage CRS. Ensure patients are euvolemic prior to initiating the infusions. Closely monitor patients for signs or symptoms of CRS following infusions of KIMMTRAK. Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy. Withhold or discontinue KIMMTRAK depending on persistence and severity of CRS.

Skin Reactions

Skin reactions, including rash, pruritus, and cutaneous edema occurred in 91% of patients treated with KIMMTRAK. Monitor patients for skin reactions. If skin reactions occur, treat with antihistamine and topical or systemic steroids based on persistence and severity of symptoms. Withhold or permanently discontinue KIMMTRAK depending on the severity of skin reactions.

Elevated Liver Enzymes

Elevations in liver enzymes occurred in 65% of patients treated with KIMMTRAK. Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total blood bilirubin prior to the start of and during treatment with KIMMTRAK. Withhold KIMMTRAK according to severity.

Embryo-Fetal Toxicity

KIMMTRAK may cause fetal harm. Advise pregnant patients of potential risk to the fetus and patients of reproductive potential to use effective contraception during treatment with KIMMTRAK and 1 week after the last dose.

The most common adverse reactions (≥30%) in patients who received KIMMTRAK were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. The most common (≥50%) laboratory abnormalities were decreased lymphocyte count, increased creatinine, increased glucose, increased AST, increased ALT, decreased hemoglobin, and decreased phosphate.

Please see full Prescribing Information, including BOXED WARNING for CRS.

About ImmTAC® Molecules
Immunocore’s proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilising monoclonal TCRs Against Cancer) molecules that are designed to redirect the immune system to recognise and kill cancerous cells. ImmTAC molecules are soluble TCRs engineered to recognise 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 tumours, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumours, regardless of mutational burden or immune infiltration, including immune “cold” low mutation rate tumours. 

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 five clinical stage programs in oncology and infectious disease, advanced pre-clinical programs in autoimmune disease and multiple earlier pre-clinical programs. Immunocore’s most advanced oncology TCR therapeutic, KIMMTRAK (tebentafusp-tebn), has been approved by the U.S. FDA for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM) having demonstrated an overall survival benefit in a randomized Phase 3 clinical trial in metastatic uveal melanoma, a cancer that has historically proven to be insensitive to other immunotherapies.

References
¹Nathan P., et al. Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2021; 385:1196-1206.

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. 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 European Commission’s final decision on Immunocore’s Marketing Authorisation Application and approval of KIMMTRAK in the European Union; marketing and therapeutic potential of KIMMTRAK for metastatic uveal melanoma (mUM); the expected clinical benefits of KIMMTRAK including extended overall survival benefit; expectations regarding the ability to reach patients in a timely manner including receiving future regulatory approval in respective European countries, the United Kingdom, Australia and Canada; the value proposition of KIMMTRAK in mUM and benefit as an orphan indication including expectations regarding the potential market size opportunity; Immunocore’s sales and marketing plans in the United States and the European Union; and future development plans of tebentafusp, including the timing or likelihood of expansion into additional markets or geographies. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual 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 the ongoing COVID-19 pandemic and the Omicron variant on the Company’s business, strategy clinical trials and financial position; Immunocore’s ability to maintain regulatory approval of KIMMTRAK; its ability to execute its commercialization strategy for KIMMTRAK; its ability to develop, manufacture and commercialize its other product candidates including plans for future development of tebentafusp and other product candidates, including the timing or likelihood of expansion into additional markets or geographies; commercial supply of KIMMTRAK or any future approved products, and launching, marketing and selling of KIMMTRAK or any future approved products; Immunocore’s ability and plans in continuing to establish and expand a commercial infrastructure and to successfully launch, market and sell KIMMTRAK; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials or future regulatory approval; Immunocore’s ability to obtain, maintain and enforce intellectual property protection for KIMMTRAK or any product candidates it is developing; unexpected safety or efficacy data observed during preclinical studies or clinical trials; clinical trial site activation or enrollment rates that are lower than expected; changes in expected or existing competition; Immunocore’s ability to obtain, maintain and enforce intellectual property protection for KIMMTRAK or any product candidates it is 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 20-F for the year ended December 31, 2020 filed with the Securities and Exchange Commission on March 25, 2021, 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: 

Immunocore
Debra Nielsen, Head of Communications
T: +1 (610) 368-8602
E: debra.nielsen@immunocore.com
Follow on Twitter: @Immunocore

Consilium Strategic Communications (corporate and financial)
Mary-Jane Elliott/ Chris Welsh/Jessica Hodgson
T: +44 (0)203 709 5700
E: Immunocore@consilium-comms.com

Investor Relations  
Clayton Robertson, Head of Investor Relations
T: +1 215-384-4781
E: ir@immunocore.com

FAQ

What is the significance of the CHMP's positive opinion for IMCR?

The CHMP's positive opinion for Immunocore (IMCR) regarding KIMMTRAK signifies a major step toward approval for a new treatment option in Europe, the first for metastatic uveal melanoma.

How does KIMMTRAK improve overall survival for uveal melanoma patients?

KIMMTRAK has shown a statistically significant overall survival benefit in clinical trials, with a hazard ratio of 0.51, indicating improved outcomes for patients with unresectable or metastatic uveal melanoma.

When is KIMMTRAK expected to be available in Europe?

KIMMTRAK's availability in Europe will depend on the final decision from the EMA following the CHMP's positive opinion, which represents a critical step in the regulatory process.

What was the FDA's role regarding KIMMTRAK?

The FDA approved KIMMTRAK on January 25, 2022, making it the first therapy for unresectable or metastatic uveal melanoma in the United States.

What does the EMA's accelerated assessment mean for KIMMTRAK?

The EMA's accelerated assessment indicates that KIMMTRAK is considered to offer significant public health benefits, expediting its review process for potential approval.