Immunocore presents KIMMTRAK clinical data demonstrating that patients with stable disease and confirmed tumor reduction have similar clinical outcomes to patients with partial response
Data were presented at ASCO 2024, where Immunocore also presented Phase 1 data from its PRAME trial with brenetafusp (IMC-F106C) in advanced cutaneous melanoma
(OXFORDSHIRE, England & CONSHOHOCKEN, PA & ROCKVILLE, MD, US, June 1, 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, today presented three posters about KIMMTRAK (tebentafusp-tebn) for the treatment of patients with unresectable or metastatic uveal melanoma (mUM) at the 2024 ASCO (American Society for Clinical Oncology) Annual Meeting. These data showed that treatment benefit for patients with stable disease and any confirmed tumor reduction was similar to patients with partial response.
"In both Phase 2 and Phase 3 KIMMTRAK trials, patients with stable disease and durable tumor reduction, regardless of depth, had similar benefit as patients with RECIST partial response," said Mohammed Dar, Senior Vice President, Clinical Development, and Chief Medical Officer, Immunocore. "The data presented at ASCO builds upon the mounting evidence confirming that disease control is the best early radiographic measure of clinical benefit across our ImmTAC platform."
"KIMMTRAK is now the standard of care, in launched countries, for HLA-A*02:01-positive patients with metastatic or unresectable uveal melanoma," said Ralph Torbay, Immunocore's Chief Commercial Officer. "Physicians can now leverage these data, presented at ASCO today, to positively inform their conversations with patients who have stable disease and minor reductions in tumor size."
Of the 127 patients treated with KIMMTRAK in the Phase 2 trial (IMCgp100-102), 25% (32/127) had any tumor reduction that was confirmed in at least one subsequent scan, including 6 partial responses (PR), an overall response rate of 5%, and 20% (26/127) stable disease (SD). The clinical outcomes in the 26 patients with SD were similar to the 6 PR patients, including durable duration of tumor reduction or response, ctDNA molecular response, and overall survival. In the Phase 3 trial (IMCgp100-202), KIMMTRAK-treated patients with SD who had any confirmed tumor reduction had durability of tumor reduction of 11 months, which was the same as the durability of response for patients with RECIST PR or CR.
Full poster details:
Stable disease with confirmed tumor reduction has a similar clinical outcome as RECIST partial response for tebentafusp in metastatic uveal melanoma
Presenting author: Alexandra Ikeguchi
Association between clinical and disease characteristics and detectable or undetectable baseline ctDNA in patients with metastatic uveal melanoma
Presenting author: Paul Nathan
Baseline and serial ctDNA dynamics predicts outcomes in patients treated with first-line tebentafusp including those who were and were not treated beyond progression
Presenting author: Ryan Sullivan
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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.
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 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.
About Phase 2 IMCgp100-102 Trial
IMCgp100-102 (NCT02570308) was an open-label, multi-center, single-arm trial of the safety and efficacy of tebentafusp in patients with previously treated mUM. The trial included 127 HLA-A*02:01+ 2L+ mUM patients, treated with tebentafusp at the recommended Phase 2 dose of 68mcg following intra-patient dose escalation of 20 mcg (week 1) and 30 mcg (week 2). The primary endpoint was objective response rate by blinded independent central review, with secondary objectives being overall survival (OS) and safety in 127 patients who had enrolled after progressing on one or more prior therapies.
About Phase 3 IMCgp100-202 Trial
IMCgp100-202 (NCT03070392) is a randomized pivotal trial that evaluated overall survival (OS) of KIMMTRAK 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 SAFETY INFORMATION
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.