On June 3, 2023 Immunocore Holdings plc (Nasdaq: IMCR), 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, infectious diseases and autoimmune conditions, reported two posters at the 2023 American Society for Clinical Oncology meeting (Press release, Immunocore, JUN 3, 2023, View Source [SID1234632420]):
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A poster including an analysis of circulating tumor DNA (ctDNA) data from the Phase 3 KIMMTRAK (tebentafusp-tebn) trial in HLA-A*02:01 patients with metastatic uveal melanoma (mUM)
A trial-in-progress poster describing the design of the Phase 2/3 trial with tebentafusp as monotherapy and in combination with pembrolizumab in HLA-A*02:01 patients with previously treated advanced melanoma.
"We have shown that KIMMTRAK can deliver significant OS benefit to patients with metastatic uveal melanoma, regardless of best RECIST response. We have now validated ctDNA reduction as an early surrogate for OS in two separate clinical trials," said Koustubh Ranade, Vice President of Translational Medicine at Immunocore. "ctDNA reduction is one of the dual endpoints in our ongoing Phase 2/3 trial with tebentafusp in patients with previously treated advanced or metastatic melanoma."
In this analysis of the Phase 3 data for patients with best response of stable disease treated with KIMMTRAK, ctDNA reduction by week 9 was observed in 94% of patients (34/36) with detectable ctDNA at baseline, and this reduction was associated with longer overall survival (OS). These data were consistent with those presented at AACR (Free AACR Whitepaper) 2023 in showing that ctDNA reduction by week 9 was strongly associated with improved OS, even in patients with best RECIST response of progressive disease – further indicating that RECIST responses underestimate tebentafusp’s clinical benefits, and that early reduction in ctDNA may be a better predictor of long OS than radiographic response.
The Company also presented a trial-in-progress poster for the Phase 2/3 trial that has started randomizing patients with previously treated advanced melanoma, excluding uveal melanoma, who have progressed on an anti-PD1, received prior ipilimumab and, if applicable, received a BRAF kinase inhibitor. Patients will be randomized to one of three arms including tebentafusp, as monotherapy or in combination with an anti-PD1, and a control arm.
Poster details
Title: Early ctDNA reduction may identify patients with stable disease and long OS on tebentafusp
Presenting author: Dan Feng
Session: Melanoma/Skin cancers
Title: A Phase 2/3 trial in progress on tebentafusp as monotherapy and in combination with pembrolizumab in HLA-A*02:01+ patients with previously treated advanced, non-uveal melanoma
Presenting author: Diwakar Davar
Session: Melanoma/Skin cancers (Trial in Progress)
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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 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.
For more information, please see full Summary of Product Characteristics (SmPC) or full U.S. Prescribing Information (including BOXED WARNING for CRS).