EVORPACEPT (ALX148), A CD47 MYELOID CHECKPOINT INHIBITOR, IN PATIENTS WITH HEAD AND NECK SQUAMOUS CELL CARCINOMA (HNSCC) AND WITH GASTRIC/GASTROESOPHAGEAL CANCER (GC); ASPEN-01

Background Evorpacept is a high affinity, CD47-blocking, myeloid checkpoint inhibitor (CPI) with an inactive Fc region designed to safely enhance anticancer therapeutics.1-3 In combination with standard chemotherapy and antibody regimens, evorpacept was evaluated in patients with advanced HNSCC or HER2-positive GC. Methods Patients with untreated advanced HNSCC or previously treated HER2-positive GC received evorpacept (E) 10 mg/kg QW or 15 mg/kg QW in combination with pembrolizumab (P) + 5FU (F) + cisplatin or carboplatin (C) as 1st line therapy, or in combination with trastuzumab (T) + ramucirumab (R) + paclitaxel (P) as ≥2nd line treatment. The primary endpoint was first-cycle dose limiting toxicity (DLT). Tumor response, pharmacokinetic, and pharmacodynamic markers were assessed in all patients. Data from fully-enrolled HNSCC and GC cohorts, and follow-up data from patients with HNSCC administered EP are reported as of 15Jun2021. Results Forty-one patients fully enrolled the following study cohorts: Thirteen patients with 1L HNSCC received EPFC. No DLTs were reported and the evorpacept maximum administered dose (MAD) was 15 mg/kg QW. Thirteen patients experienced an AE, 2 patients experienced treatment-related AEs (TRAE) of pneumonitis, anemia, fatigue, neutropenia, and hypersensitivity reaction (each n=1, 7.7%). Of 13 evaluable patients, 1CR/4PR/6SD (ORR 38.5%), mPFS 5.6 mo [3.6,NR], mOS not reached, and estimated 12-month OS of 83.3% were reported. Survival follow-up of 10 patients with CPI naive HNSCC administered EP (2nd or later-line; ORR 40%) demonstrated a mPFS 4.6 mo [0.5,7.5], mOS 24.5 mo [3.1,NR] and estimated 12-month OS of 80%.Eighteen patients with ≥2L GC received ETRP. No DLTs were reported and the evorpacept MAD was 15 mg/kg QW. All patients experienced an AE, 8 patients experienced TRAEs, where the most common were urticaria, rash, and diarrhea (each n=3, 17%), fatigue and pruritus (each n=2, 11%). Of 18 evaluable patients, there were 1CR/12PR/3SD (ORR 72.2%; mDOR unreached) with a mPFS 9.8 mo [5.4,NR], mOS not reached, and estimated 12-month OS of 77.7%. Conclusions Initial data suggest evorpacept is well tolerated with no DLTs in combination with the antibody/cytotoxic chemotherapy regimens evaluated above and a MAD of 15 mg/kg QW. Consistent with standard CPI therapeutic agents, the initial response benefit seen with evorpacept in combination is notably magnified in longer term PFS and OS endpoints in both the HNSCC and GC populations. Evorpacept’s preliminary positive impact on critical survival endpoints compares favorably with historical standards and warrants further evaluation in patients with HNSCC and GC. Acknowledgements We would like to thank all of the participating patients, their families and site research teams. Trial Registration ClinicalTrials. gov identifier NCT03013218. References Kauder S, et al. ALX148 blocks CD47 and enhances innate and adaptive antitumor immunity with a favorable safety profile. PLoS ONE 2018;13(8). Chow L, et al. A phase I study of ALX148, a CD47 blocker, in combination with standard anticancer antibodies and chemotherapy regimens in patients with advanced malignancy. Journal of Clinical Oncology 2020;38:15_suppl, 3056–3056. Chung H et al, ASPEN-01: A Phase 1 study of ALX148, a CD47 blocker, in combination with trastuzumab, ramucirumab and paclitaxel in patients with 2nd line HER2-positive advanced gastric or gastroesophageal junction (G/GEJ) cancer. ESMO-GI 2021; #SO-31. Ethics Approval The study was approved by all participating institutions’ Ethics and/or Review Boards