공시 • Apr 20
Immunocore Holdings Plc Announces Five-Year Overall Survival Results For KIMMTRAK In Metastatic Uveal Melanoma
Immunocore Holdings plc announced that KIMMTRAK® (tebentafusp-tebn) five-year overall survival (OS) was presented in an oral session at the American Association for Cancer Research (AACR) 2026 meeting. This is the longest, prospective Phase 3 randomized trial in patients with unresectable or metastatic uveal melanoma (mUM) – a disease with a very poor prognosis and a historical survival rate of <5% at 5 years. KIMMTRAK doubled the likelihood of being alive at five years, with an OS for KIMMTRAK of 16% versus 8% in the control arm (hazard ratio [HR] of 0.67 [95% CI: 0.54-0.85]). These results also represent the longest follow-up reported for any T cell engager in a solid tumor. In the trial, 378 patients were randomized to tebentafusp (252) or investigator’s choice (126; 82% pembrolizumab). The median OS was 21.6 months on KIMMTRAK, versus 16.9 months on investigator’s choice (IC). The Kaplan–Meier survival curves separated early and remained separated over time, confirming the durability of the benefit with extended follow-up. The data confirmed that the OS benefit was primarily driven by tebentafusp rather than subsequent therapies. Among patients treated with KIMMTRAK who were alive at five years, nearly half (44%) received only KIMMTRAK, while among patients in the control arm alive at the same time point, 86% subsequently received tebentafusp. The OS benefit with KIMMTRAK was observed regardless of known poor prognostic factors at baseline (high tumor burden [=10cm]; elevated lactate dehydrogenase [LDH]) or tumor location (hepatic only; hepatic and extra-hepatic). OS benefit was also observed in patients with a best response of progressive disease, including those with >20% tumor growth as best change on treatment. More patients continued treatment beyond progression in the KIMMTRAK arm than in the control arm (57% vs 25%) – with the trial allowing this option in both arms. Patients on KIMMTRAK achieved nearly a 7-fold higher rate of tumor reduction with treatment beyond initial progression compared to IC patients (27% vs 4%). Patients who continued tebentafusp treatment beyond tumor progression experienced longer post-progression survival compared to those who stopped treatment, even after accounting for variations in patient characteristics. In tebentafusp-treated patients, longer OS was associated with undetectable ctDNA at baseline or ctDNA reductions =50% by week 9. Among 21 ctDNA-evaluable patients who survived = 5 years, 71% had undetectable baseline ctDNA and 29% had ctDNA clearance by week 9. Deep reductions in ctDNA were seen across all RECIST categories. Early ctDNA molecular response continues to be a more sensitive marker of tebentafusp activity than radiographic measurements. The data were presented in an oral session during the AACR 2026 meeting: Title: Five-year survival with tebentafusp in previously untreated metastatic uveal melanoma in a Phase 3 trial (CT029) Session: Advanced Cellular and Immune-Based Therapeutics. 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. 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. 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, 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. 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. 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.