3667 - Phase 1, Open-Label Ascending Dose Trial of Anti–CTLA-4 Monoclonal Antibody AGEN1884 in Advanced Solid Malignancies, With Expansion to Patients Refractory to Recent Anti–PD-1/PD-L1 Therapy

Background

AGEN1884 is a novel anti–cytotoxic T-lymphocyte-associated antigen (CTLA)-4 fully human immunoglobulin (IgG)-1 monoclonal antibody. Objective: Assess safety, maximum tolerated dose, and pharmacokinetics (PK)/pharmacodynamics of AGEN1884 in patients (pts) with advanced/refractory malignancies and in pts refractory to recent anti–programmed death 1 (PD-1)/PD-L1 therapy.

Methods

Adult pts with relapsed/refractory lymphoma or solid tumors received AGEN1884 at 0.1, 0.3, 1, 3, or 6 mg/kg (3 + 3 design). 10 more pts each were enrolled in 1 and 3 mg/kg expansion cohorts. 10 pts with disease progression after prior treatment with approved or investigational PD-1/PD-L1 inhibitor as most recent therapy (2–5 weeks [wks] before first study drug) will be enrolled at 1 mg/kg. AGEN1884 was administered intravenously Q3 wks for 4 doses, then Q3, 6, or 12 wks at investigator’s discretion.

Results

33 pts enrolled as of 03Jan2018: 0.1 mg/kg (n = 5; 2 not evaluable [NE] for dose-limiting toxicity [DLT]); 0.3 mg/kg (n = 3); 1 mg/kg (n = 10); 3 mg/kg (n = 12; 2 NE for DLT); 6 mg/kg (n = 3). Median age: 61 y (range 26–88); baseline ECOG scores: 0 (n = 4), 1 (n = 25), unknown (n = 4); median 10 (range 3–26) prior therapies. No DLTs reported as of 31Jan2018. Immune-related adverse events (AEs) reported in 10 (30.3%) pts: 0.1 mg/kg (1, 20.0%), 0.3 mg/kg (1, 33.3%), 1 mg/kg (1, 10%), 3 mg/kg (6, 50%); included hypophysitis, colitis, diarrhea, rash, pruritus. Most were mild-moderate, consistent with other CTLA-4 inhibitors. 6 (18.2%) pts came off study due to disease progression or AEs, none treatment-related. Of 11 pts evaluable for response, 1 had complete response (angiosarcoma, 0.1 mg/kg). Stable disease (SD) in 3 pts: 1 with adenoid cystic carcinoma (0.3 mg/kg, 53 wks of SD) and 2 with breast cancer (3 mg/kg, SD at wks 6 and 12, respectively).

Conclusions

AGEN1884 was well tolerated at 0.1, 0.3, 1, and 3-mg/kg dose levels. Enrollment is ongoing at 6 mg/kg. Updated safety, PK, and results for the anti–PD-1/PD-L1 refractory expansion cohort will be presented. A starting dose of 1 mg/kg is being evaluated in ongoing trials in combination with PD-1 blockade.

Clinical trial identification

NCT02694822.

Legal entity responsible for the study

The licensed antibody AGEN1884 was originally developed under a Collaborative Research and Development Agreement between Ludwig Cancer Research, 4-Antibody AG (now Agenus Switzerland Inc.) and Recepta Biopharma S.A. This antibody is partnered with Recepta Biopharma S.A. for certain South American rights.

Funding

This analysis was funded by Agenus Inc. (Lexington, MA, USA).

Editorial Acknowledgement

Editorial support was provided by The Medicine Group, LLC (New Hope, PA, USA) and funded by Agenus Inc. (Lexington, MA).

Disclosure

B.A. Wilky: Employment: Novartis, Janssen Oncology, Lilly; Travel, accommodations, expenses: Novartis, Lilly, Advenchen Laboratories; Research funding: Novartis, Merck Sharp & Dohmn, Daiichi Sankyo, ArQule, Agenus. R. Wesolowski: Consulting or advisory role: Novartis, Agenus, Pfizer; Research funding: Acerta Pharma. J.J. Hwang: Consulting or advisory role: Genentech/Roche, Amgen, Bayer, Taiho Pharmaceutical, Bristol-Myers Squibb, Boehringer Ingelheim, Ipsen; Speakers bureau: Genentech/Roche, Amgen, Celgene, Ipsen, Bristol-Myers Squibb. G. Yuan, M. Lim, J-M. Cuillerot, J.J. Raizer, E. Drouin, N. Wilson, A.M. Gonzalez, J.M. Goldberg, J.S. Buell, R.B. Stein, H. Youssoufian: Employee: Agenus Inc. or subsidiary there of (current or former employee), Lexington, MA. C.D. Dupont: Employee: Agenus Inc. or subsidiary there of (current or former employee), Lexington, MA; An immediate family member: Employee: Vertex; An immediate family member: Employee: Rochester Eye Associates; Travel, accommodations, expenses: Agenus; Research funding: Agenus; An immediate family member: Vertex, Pfizer, Sanofi. Stock and other ownership: Agenus; An immediate family member: Vertex. O. Shebanova: Employee: Agenus Inc. or subsidiary there of (current or former employee), Lexington, MA; Travel, accommodations, expenses: Agenus; Stock and other ownership: Agenus. E. Dow: Employee: Agenus Inc. or subsidiary there of (current or former employee), Lexington, MA; Employment: Baxalta/Shire; Foundation Medicine stock and other ownership: Baxalta/Shire, Foundation Medicine. W. Ortuzar: Full time contracted consultant: Agenus Bio, Inc. All other authors have declared no conflicts of interest.