743P - A phase Ib dose escalation study of CD137 mAb agonist OC-001 as monotherapy in patients with advanced or metastatic cancer

Background

OC-001 is a CD137 mAb agonist designed to show differential agonistic activity from that of competitor antibodies. OC-001 provided T cell activation that results in antitumor efficacy in humanized mouse tumor models in vivo.

Methods

This ongoing 2-part, open-label, multi-center study. The primary objective of this study is to assess the safety and tolerability of OC-001 administered as a monotherapy in patients with selected locally advanced or metastatic cancer. Secondary objectives are to: 1) Evaluate the PK of OC-001 in monotherapy and in combination therapy with an anti-PD-L1 mAb; 2) Evaluate the safety of OC-001 + anti-PD-L1 mAb; and 3) Evaluate the anti-tumor activity of OC-001 + anti-PD-L1 mAb. Patients receive OC-001 i.v. Q2W (0.5 mg, 4 mg, 30 mg, 150 mg, 300 mg, and 600 mg) in 28-day cycles in a 3+3 dose escalation design.

Results

Fifteen evaluable patients are included in this analysis. Doses up to 150 mg have been evaluated to date and the MTD has not been reached. Importantly, OC-001 has not shown liver toxicity in the doses tested to date. Biomarkers of immune activation or T cell exhaustion are being analyzed to determine the appropriate recommended phase 2 dose (RP2D). One dose-limiting toxicity of worsening general condition has been observed to date at the 4mg dose. The main reported treatment emergent adverse events were nausea, constipation, decreased appetite, abdominal pain, and fatigue. The mean half-life was about 250 hours after Cycle 2. Linear PK profiles are observed for the 0.5 mg, 4 mg, 30 mg, and 150 mg OC-001 dose levels. C_max and AUC exposures appear dose proportional over the dose range of 0.5 mg to 150 mg OC-001. Based on C_min values, steady state appears to be reached between Cycle 2 Day 15 and Cycle 4 Day 1 with C_min accumulation ratios of 2.7 or lower. Five patients had a best response of SD for a duration of ≥ 6 cycles.

Conclusions

OC-001 was tolerated at doses up to 150 mg Q2W. The mAb has predicable PK characteristics. OC-001 is a potential candidate for combination therapy with immune-oncology agents.

Clinical trial identification

NCT04260802.

Editorial acknowledgement

Legal entity responsible for the study

Ocellaris Pharma Inc.

Funding

Ocellaris Pharma Inc.

Disclosure

W.H. Miller: Financial Interests, Personal and Institutional, Advisory Board, Speaker,s bureau: Merck, BMS, Roche, GSK, Novartis, Amgen, Mylan, EMD Serono, Sanofi; Financial Interests, Institutional, Research Grant: Merck, Mimic, Astellas, BMS, Novartis, GSK, Incyte, Pfizer, Sanofi, Ocellaris Pharma, Alkermes, Genentech, Esperas Pharma, Array, Exilixis, Velos Bio. D. Provencher: Financial Interests, Institutional, Principal Investigator: Ocellaris Pharma, Esperas Pharma. Q.S. Chu: Financial Interests, Personal and Institutional, Advisory Board, Clinical Trials and Grants: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Alkermes, Bicycle, GSK, Mirati, Ocellaris Pharma, Revolution Medicine, Treadwell, TP Therapeutics; Financial Interests, Personal and Institutional, Principal Investigator, Advisory Board: Amgen, Astellas, BMS, Boehringer Ingelheim, Eli Lilly, Esperas Pharma, Merck, Novartis, Pfizer; Financial Interests, Personal and Institutional, Principal Investigator: Exactis; Financial Interests, Personal, Advisory Board: AbbVie, Esai, J&J, Jazz, Roche, Takeda. D. Jonker: Financial Interests, Institutional, Principal Investigator: Ocellaris Pharma. A.M. Oza: Financial Interests, Institutional, Principal Investigator: Ocellaris Pharma, Esperas Pharma. R. Jamal: Financial Interests, Institutional, Principal Investigator: BMS, Merck, Iovance. R. Goel: Financial Interests, Institutional, Principal Investigator: Ocellaris Pharma. J.F. Hilton: Financial Interests, Personal, Advisory Board: Merck, Novartis, AstraZeneca, Pfizer, Eli Lilly; Financial Interests, Personal, Invited Speaker: Merck, Novartis; Financial Interests, Personal, DSMC committee - relatlimab program: BMS; Financial Interests, Personal, Research Grant: GSK. J. Spratlin: Financial Interests, Personal and Institutional, Principal Investigator, Advisory Board: AstraZeneca, Taiho, Celgene, Incyte, Amgen, BMS. P. Smith: Financial Interests, Personal, Employee: Eli Lilly. J. Stille: Financial Interests, Personal, Employee: Eli Lilly. C. Fortier: Financial Interests, Personal, Officer: Ocellaris Pharma Inc, Esperas Pharma Inc.. J. Polzer: Financial Interests, Personal, Advisory Role: Ocellaris Pharma, Esperas Pharma. All other authors have declared no conflicts of interest.