4258 - Phase 1/2 Study of CTLA-4 Inhibitor AGEN1884 + PD-1 Inhibitor AGEN2034 in Patients With Advanced/Refractory Solid Tumors, With Expansion Into 2L Cervical Cancer and Solid Tumors

Background

Cytotoxic T-lymphocyte-associated antigen (CTLA)-4 and programmed death 1 (PD-1) pathways have important, distinct roles in T-cell modulation; blockade of both has been synergistic in vitro and in the clinic. This study will assess safety and tolerability of AGEN1884 (anti–CTLA-4 human immunoglobulin [IgG]-1 monoclonal antibody [mAb]) in combination with AGEN2034 (anti–PD-1 human IgG4 mAb) in patients (pts) with advanced/refractory solid tumors, with expansion into select solid tumors.

Methods

A dose-escalation phase and expansion focusing on adult female pts with recurrent/metastatic cervical cancer that has relapsed after platinum-containing doublet treatment. Phase 1 (Ph1) pts (n = 20) will be enrolled to 2 dose regimens of AGEN1884 + AGEN2034 (starting: 1 mg/kg AGEN1884 Q6w + 1 mg/kg AGEN2034 Q2w; escalating: 1 mg/kg AGEN1884 Q6w + 3 mg/kg AGEN2034 Q2w). Escalation phase primary endpoints: safety, determination of recommended Ph2 dose (RP2D); Ph2 (n = 40) also includes best overall response assessment by Independent Endpoint Review Committee per RECIST 1.1. Secondary endpoints: AGEN1884 and AGEN2034 pharmacokinetic (PK)/pharmacodynamic (PD) profiles, objective response rate, duration of response, progression-free and overall survival.

Results

0 pts were enrolled 01Dec2017–10Apr2018 in 3 Australia centers: 7 pts at starting dose, 3 pts at escalating dose. No dose-limiting toxicity has been observed; most common toxicities observed were expected for therapeutic class. 8 pts experienced toxicity, mostly grade 1 or 2. Most common toxicities: diarrhea/nausea/vomiting, n = 6; rash/pruritus, n = 2; transaminases elevated, n = 1; fever/flu-like, n = 3; fatigue, n = 2. There was 1 serious adverse event and grade 3 toxicity unrelated to study drug. No discontinuation due to study drug, no deaths observed. Median dose administered was 1 for AGEN1884, 3 for AGEN2034. Dose level 2 was determined for RP2D. Updated safety, efficacy, and PK/PD of AGEN1884 + AGEN2034 will be presented.

Conclusions

AGEN1884 (1 mg/kg Q6w) + AGEN2034 (3 mg/kg Q2w) is well tolerated and being evaluated in Ph2 combination in 2L cervical cancer and other solid tumors.

Clinical trial identification

ACTRN12618000003279.

Legal entity responsible for the study

The licensed antibodies AGEN1884 and AGEN2034 were 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. These antibodies are partnered with Recepta Biopharma S.A. for certain South American rights.

Funding

Agenus Inc. (Lexington, MA, USA).

Editorial Acknowledgement

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

Disclosure

J. Coward: Amgen: ESMO conference 2018 sponsorship MSD: Tumour agnostic advisory board Dec 2017. C.D. Dupont: Agenus Inc. or subsidiary there of (current or former employee), Lexington, MA Vertex-An Immediate Family Member Rochester Eye Associates- An Immediate Family Member; Travel, accommodations, expenses: Agenus Research Funding: Agenus; Vertex-family member Pfizer Sanofi Stock and other ownership: Agenus Vertex-family member. A.M. Gonzalez, M. Lim, D. Savitsky, M. Carini, S. Hu, H. Youssoufian: Agenus Inc. or subsidiary there of (current or former employee), Lexington, MA. O. Shebanova: Agenus Inc. or subsidiary there of (current or former employee), Lexington, MA Travel, Accommodations, Expenses Agenus Stock and other ownership: Agenus. E. Dow: 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 for Agenus Bio, Inc. J.S. Buell: Agenus Inc. or subsidiary there of (current or former employee), Lexington, MA Travel, Accommodations, Expenses: Agenus. R.B. Stein: Agenus Inc. or subsidiary there of (current or former employee), Lexington, MA Stock and other ownership: Agenus. All other authors have declared no conflicts of interest.