2946 - Preliminary results of PROCLAIM-CX-072: The first-in-human, dose-finding trial of PD-L1 Probody therapeutic CX-072 as monotherapy in patients (pts) with advanced solid tumors

Background

Antibodies (Abs) against programmed cell death ligand-1 (PD-L1) have improved survival in many types of cancer when used as monotherapy. However, anti–PD-L1 agents can be associated with high-grade immune-related adverse events (irAEs), particularly when used in combination with other anticancer agents. CX-072 is an anti–PD-L1 Probody™ therapeutic (Pb-Tx) designed to be preferentially activated by proteases in the tumor microenvironment and not in healthy tissue. Preclinically, Pb-Tx exhibited anticancer activity of the parent Ab with reduced toxicities in models of autoimmunity.

Methods

In parts A and A2 of the ongoing phase 1/2 Probody Clinical Assessment In Man (PROCLAIM)-CX-072 study (NCT03013491), CX-072 monotherapy is evaluated in a dose-escalation cohort of pts with advanced, heavily pretreated solid tumors. Part A2 required PD-L1-positive tumors and paired biopsies. Eligible pts were PD-1, PD-L1, and CTLA-4 inhibitor naive, with immunotherapy (IMT) unavailable as a standard of care. CX-072 is given every 14 days in cohorts of intravenous doses ranging from 0.03-30 mg/kg.

Results

As of April 20, 2018, part A/A2 had enrolled 37 pts. Pts had a median (range) of 3 (1-13) prior anticancer treatments. 14 (37.8%) pts are still on treatment at time of data cut. Median (range) time on treatment was 2.1 months (1-10). One DLT was observed (grade 3 febrile neutropenia; 3 mg/kg); MTD was not reached. Grade 3-4 treatment-related events were observed in 4 (10.8%) pts. irAEs with reversible grade 3 events occurred in 3 patients: thrombocytopenia, aminotransferase increases, and dyspnea. Two subjects discontinued CX-072 due to AEs. Across all dose levels, best response based on investigators’ assessment in 23 evaluable pts included 2 partial response (thymoma, 3 mg/kg; TNBC, 10 mg/kg), 10 stable disease, and 11 progressive disease.

Conclusions

Preliminary data suggest that CX-072 demonstrates the characteristics of an antibody prodrug with antitumor activity and an acceptable safety profile in heavily pretreated pts with IMT-naive solid tumors. These data warrant further exploration of CX-072 as monotherapy and in combination with other anti-cancer agents.

Clinical trial identification

NCT03013491.

Legal entity responsible for the study

CytomX Therapeutics, Inc.

Funding

CytomX Therapeutics, Inc.

Editorial Acknowledgement

Editorial support was provided by Andrew Occiano (ApotheCom, San Francisco, CA).

Disclosure

P.A. Ott: Research grant: BMS, Merck, Celldex, MedImmune, CytomX, ArmoBiosciences, Neon Therapeutics; Consulting: BMS, Merck, Celldex, CytomX, Roche/Genentech, Pfizer, Novartis, Neon Therapeutics; Nonremunerative positions of influence: NCCN melanoma guidelines board member. D.C. Cho: Consulting: BMS, Pfizer, Exelixis, Genentech, Prometheus. K.A. Autio: Research funding: CytomX, Pfizer, Lilly, GSK, Merck, ARMO Biosciences. N. Uboha: Consulting: EMD Serono, Lilly, FlatIron, GLG. A.I. Spira: Research grant: AbbVie; Consulting: AbbVie. R. Humphrey, M. Will: Employee: CytomX. A. Naing: Research funding: NCI, EMD Serono, MedImmune, Healios Onc. Nutrition, Atterocor, Amplimmune, ARMO Biosciences, Karyopharm Therapeutics, Incyte, Novartis, Regeneron, Baxter (spouse). F. Thistlethwaite: Research grant: Novartis; Consulting: Pfizer, BMS, Octimet, Achilles Therapeutics, Evelo Biosciences; Honorarium: Novartis; Speakers' bureau: BMS. E.G.E. de Vries: Research grant (institution): Amgen, Genentech, Roche, Chugai, Synthon, CytomX, Nordic Nanovector, Regeneron, G1 Therapeutics, AstraZeneca, Radius Health; Consulting (institution): Pfizer, Sanofi. All other authors have declared no conflicts of interest.