CX-072, a PD-L1 Probody therapeutic, as monotherapy in patients with advanced solid tumors: Preliminary results of PROCLAIM-CX-072.

Abstract

2513 Background: Anti-programmed cell death ligand 1 (PD-L1) immunotherapies have improved survival in many cancers, but immune-related adverse events (irAEs) have been observed, especially in combination therapy. CX-072 is an investigational Probody therapeutic directed against PD-L1, designed to be preferentially activated in the tumor microenvironment and to reduce irAEs. Methods: This is an ongoing phase 1/2a study (PROCLAIM-CX-072; NCT03013491) evaluating CX-072 in patients (pts) with metastatic or unresectable solid tumors with no further standard curative treatment options and with no prior anti-PD1, PD-L1 or anti-CTLA4 treatment. Pts were unselected for PD-L1 expression. We report preliminary results from expansion cohorts in anal squamous cell carcinoma (SCCA), cutaneous squamous cell carcinoma (cSCC), small bowel adenocarcinoma (SBA), triple-negative breast cancer with skin lesions (TNBC), or undifferentiated pleomorphic sarcoma (UPS). Pts were treated with CX-072 monotherapy 10 mg/kg intravenously every 14 days. Results: As of 30 Nov 2018, 51 pts received CX-072 10 mg/kg monotherapy: SCCA (n = 9), cSCC (n = 5), SBA (n = 9), TNBC (n = 9), and UPS (n = 19). Median age was 63 y (range, 32-80), 67% were female, and pts had a median of 3 prior regimens (range, 1-12). Median treatment duration was 1.8 mo (range, 0.3-14.7). A grade 3/4 treatment-related adverse event (AE) was observed in 1 pt (2%; gr 3 generalized rash). No grade 3/4 irAEs were observed. Two pts discontinued treatment due to AEs: nausea (pt with SCCA) and sepsis (pt with SBA), neither treatment-related. Partial responses (confirmed and unconfirmed) were observed in cSCC (n = 1), TNBC (n = 2), and UPS (n = 1) (Table). Conclusions: CX-072 10 mg/kg monotherapy demonstrated anticancer activity in heavily pretreated pts with advanced solid tumors, including responses in cSCC, TNBC with skin lesions, and UPS, with a safety profile that compares favorably to historical controls. Clinical trial information: NCT03013491. [Table: see text]