Phase 1 safety and efficacy of IMC-F106C, a PRAME × CD3 ImmTAC bispecific, in post-checkpoint cutaneous melanoma (CM).

person Omid Hamid The Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, CA info_outline Omid Hamid, Anja Williams, Juanita Suzanne Lopez, Daniel Olson, Takami Sato, Heather May Shaw, Claire Frances Friedman, Fiona Thistlethwaite, Mark R. Middleton, Celeste Lebbe, Vincent T Ma, Benjamin Izar, Peter Kar Han Lau, Oliver Edgar Bechter, Peter Kirk, Yuan Yuan, Shannon Marshall, Diwakar Davar

Authors person Omid Hamid The Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, CA info_outline Omid Hamid, Anja Williams, Juanita Suzanne Lopez, Daniel Olson, Takami Sato, Heather May Shaw, Claire Frances Friedman, Fiona Thistlethwaite, Mark R. Middleton, Celeste Lebbe, Vincent T Ma, Benjamin Izar, Peter Kar Han Lau, Oliver Edgar Bechter, Peter Kirk, Yuan Yuan, Shannon Marshall, Diwakar Davar Organizations The Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, CA, HCA Healthcare global Sarah Cannon Research Institute, London, United Kingdom, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom, University of Chicago, Comprehensive Cancer Center, Chicago, IL, Jefferson Medical College, Philadelphia, PA, University College London Hospital, London, United Kingdom, Memorial Sloan Kettering Cancer Center, New York, NY, The Christie NHS Foundation Trust, Manchester, United Kingdom, Medical Sciences Division, University of Oxford, Headington, Oxford, United Kingdom, Université Paris Citée, Dermatolo-Oncology AP-HP Hôpital Saint-Louis, INSERM U976, Paris, France, University of Wisconsin Carbone Cancer Center, Madison, WI, Columbia University Medical Center, New York, NY, Linear Clinical Research Ltd, Perth, Western Australia, Australia, UZ Gasthuisberg - Katholieke University Leuven, Leuven, Belgium, Immunocore, Abingdon, United Kingdom, Immunocore, Rockville, MD, Immunocore, LLC, Rockville, MD, UPMC Hillman Cancer Center, Pittsburgh, PA Abstract Disclosures Research Funding Immunocore Background: IMC-F106C is a novel ImmTAC bispecific protein (PRAME × CD3). Dose escalation results showed robust T cell activation, T cell infiltration into tumor, and clinical activity in various solid tumors (NCT04262466; Hamid 2022). We present updated CM data from monotherapy (mono) and anti-PD1 combination (combo) cohorts. Methods: HLA-A*02:01+ unresectable/metastatic (m) CM patients (pts) previously treated with immune checkpoint inhibitors (ICI) were eligible. Primary objectives were safety and selection of recommended dose; additional objectives were efficacy and ctDNA response (Natera, Guardant). Stable disease (SD) with any tumor reduction confirmed with ≥ 1 subsequent scan was analyzed based on association with overall survival (OS) for tebentafusp. Molecular response was defined ≥ 0.5 log [68%] ctDNA reduction by week 9. PRAME was tested by immunohistochemistry (IHC; PRAME+ defined as H-score ≥1). Efficacy is presented by PRAME− and PRAME+ (documented + and unknown) groups. IMC-F106C dosed IV with 2 step-up doses and weekly target dose (20-320 mcg mono, 160 mcg combo). Pembrolizumab (pembro) dosed at IV 400 mg Q6W. Data cutoff: Dec 2023. Median follow-up of mono was 11 months. Results: 46 mCM pts (40 mono, 6 combo) received IMC-F106C ≥ 20 mcg. All mono pts received prior ICI (100% anti-PD1, 88% anti-CTLA4); 25% had prior BRAF/MEK inhibitors. 35/40 mono pts were grouped by IHC as positive (25 PRAME+, 10 unknown) vs. 5 PRAME−. Adverse events (AEs) were consistent with prior experience. Most common AE was Grade 1/2 CRS (50%); mostly in first 3 weeks. No drug related AEs led to treatment discontinuation or death. Safety for pembro combo to date was consistent with the individual agents. 31/40 mono pts had a RECIST evaluable tumor assessment. The clinical benefit rate (CBR) of PR + SD was 61% (19/31). 35% (11/31) had any tumor reduction that was confirmed on ≥ 1 subsequent scan, including 4 PR (ORR 13%) and 7 SD (26 of 31 pts were PRAME+; the CBR in these was 65% and included all 11 (42%) with confirmed tumor reduction. In 5 PRAME−, there was no tumor reduction. Both median progression free survival (PFS) and 6-month OS rates were higher in PRAME + vs –: 4.5 vs 2.1 months and 94% vs 40%, respectively. 12/40 mono pts received therapy for > 6 months and 14/40 mono pts remain on therapy. 41% of ctDNA-evaluable, PRAME+ mono pts had a molecular response (9/22); this was associated with longer PFS and OS. Correlative biomarkers will be shared. Conclusions: IMC-F106C was well tolerated with promising clinical activity in ICI-pretreated, mCM patients without clinical options. Clinical activity, measured by any confirmed tumor reduction and ctDNA molecular response, is enriched in PRAME+ patients at ~40% and associated with longer PFS and OS. IMC-F106C can be combined with anti-PD1. A Ph 3 trial of IMC-F106C with nivolumab in 1st line mCM has been initiated (PRISM-MEL301; NCT06112314). Clinical trial information: NCT04262466.

Clinical