433 A phase 2 study of evorpacept (ALX148) in combination with pembrolizumab and chemotherapy in patients with advanced head and neck squamous cell carcinoma (HNSCC); ASPEN-04

• Published in: Journal for immunotherapy of cancer 2021-11, Vol.9 (Suppl 2), p.A463-A463
• Main Authors: Cirauqui, Beatriz, Cohen, Ezra, Keam, Bhumsuk, Machiels, Jean-Pascal, Oosting, Sjoukje, Welliver, Tim, Guan, Shanhong, Jin, Feng, Forgie, Alison, Fanning, Philip, Ruffner, Katherine, Pons, Jaume, Randolph, Sophia, Harrington, Kevin
• Format: Article
• Language: English
• Subjects: Cancer; Chemotherapy; Cytotoxicity; Head & neck cancer; Immunotherapy; Metastasis; Monoclonal antibodies; Regular and Young Investigator Award Abstracts; Squamous cell carcinoma; Targeted cancer therapy
• ISSN: 2051-1426
• DOI: 10.1136/jitc-2021-SITC2021.433

BackgroundAnticancer immunity relies on the release of tumor antigens and subsequent activation of the innate and adaptive immune systems. After cytotoxic chemotherapy induces neoantigen release, myeloid checkpoint inhibitors can help potentiate innate immune cell activity including antigen presentation. CD47 is a marker of self that interacts with SIRPα on myeloid immune cells and is upregulated by tumors to evade immune responses. Evorpacept is a high affinity CD47-blocking fusion protein with an inactive Fc region designed to safely enhance standard anticancer therapeutics. Pembrolizumab, a T cell checkpoint inhibitor that activates cytotoxic lymphocytes, is a standard option for patients with previously untreated recurrent/metastatic (R/M) HNSCC, both as a monotherapy and in combination with 5FU + platinum. Through increased activation of the immune system, a combination of evorpacept + pembrolizumab + 5FU/platinum might have more anti-tumor activity in R/M HNSCC than current standard therapeutic approaches. This combination approach could be particularly beneficial to R/M HNSCC patients with low PD-L1 expression, where anti-PD-(L)1 therapy historically has diminished efficacy. The combination of evorpacept + pembrolizumab + 5FU/platinum has undergone preliminary testing in the ongoing Phase 1 ASPEN-01 study,1 demonstrating initial clinical response and tolerability. In previously untreated, PD-L1-unselected R/M HNSCC patients treated with evorpacept + pembrolizumab + 5FU/platinum, patients experienced objective responses, including complete response. The ASPEN-04 study will assess the efficacy and safety of evorpacept in combination with pembrolizumab and chemotherapy in previously untreated patients with PD-L1-unselected R/M HNSCC.MethodsASPEN-04 (figure 1) is an ongoing non-comparative, open-label, randomized Phase 2 global study of evorpacept + pembrolizumab + chemotherapy (5FU + either carboplatin or cisplatin) or pembrolizumab + chemotherapy in patients with PD-L1-unselected metastatic or unresectable recurrent HNSCC who have not yet been treated for their advanced disease. After an initial safety lead-in cohort, ~106 patients will be randomized to receive evorpacept + pembrolizumab + chemotherapy or pembrolizumab + chemotherapy. Minimization factors used to randomize patients include geography, PD-L1 combined positive score, and HPV (p16) status. Patients in the evorpacept treatment arm will receive evorpacept 45 mg/kg IV Q3W. All patients will