AGEN1884 (anti-CTLA-4)

AGEN1884: An anti-CTLA4 antibody, designed to inhibit CTLA-4 and restore anti-tumor immunity

CTLA-4 (cytotoxic T-lymphocyte antigen-4), is a negative regulator of immune activation that is considered a foundational target within the immuno-oncology market. In 2018, the Nobel Prize in Medicine was awarded for the establishment of CTLA-4 as a cancer immunotherapy target. Agenus has applied these scientific findings to create a therapy designed to treat cancer, AGEN1884.

AGEN1884 is a fully humanized monoclonal antibody that activates the immune system to destroy cancer cells by blocking the interaction between CTLA-4 and its binding partners CD80 and CD86.

AGEN1884 is clinically active in patients with advanced or refractory cancer. In fact, we have seen a complete and durable response in a patient with refractory angiosarcoma. This patient was profiled in the news.

Agenus’ CTLA-4 is in clinical trials as a monotherapy and a combination with our PD-1, AGEN2034 in an ongoing Phase 1/2, open-label, multi-arm trial to investigate the safety, tolerability, pharmacokinetics, biological and clinical activity of this regimen in patients with metastatic or locally advanced solid tumors including refractory cervical cancer. As of April 2020, our anti-CTLA-4 antibody in combination with our anti-PD-1 antibody has achieved 14 positive clinical responses in 55 patients with second-line cervical cancer (~26% ORR with ~12-month follow-up).

Agenus controls worldwide rights to AGEN1884, except for certain South American rights, which are controlled by Recepta Biopharma, and Greater China rights, which are exclusively licensed to Betta Pharmaceuticals.

Latest Clinical Trials

Enrolling in second-line cervical cancer


Phase 1/2, open-label study of AGEN1884 in combination with AGEN2034 in subjects with locally advanced, recurrent and/or metastatic solid tumors including cervical cancer

Enrolling in cancers that have progressed after PD-1/PD-L1 inhibitor as the most recent therapy


Phase 1/2, multicenter study to evaluate the safety, PK, and PD of an anti-CTLA-4 human monoclonal antibody (AGEN1884) in subjects with advanced or refractory cancer and in subjects who have progressed during treatment with a PD-1/PD-L1 inhibitor as their most recent therapy

Latest Publications and Abstracts

Society for Immunotherapy of Cancer (SITC)

November 9-14, 2020

Pseudoprogression (PSP) Patterns: Analysis from 2 Independent Phase-2 Studies with Immunotherapy for Recurrent Cervical Cancer. O'Malley, et al.

Society for Immunotherapy of Cancer (SITC)

November 9-14, 2020

Single-agent Zalifrelimab (anti-CTLA-4) Shows Clinical Benefit in Rare Tumors – Case Reports from a Phase 2 Study (NCT02694822). Perez, et al.

European Society for Medical Oncology (ESMO) Virtual

September 19-21, 2020

Balstilimab (anti-PD-1) Alone and in Combination with Zalifrelimab (anti-CTLA-4) for Recurrent/Metastatic (R/M) Cervical Cancer (CC) Preliminary Results of Two Independent Ph2 Trials . O'Malley, et al.

Journal for ImmunoTherapy of Cancer

August 8, 2019

Angiosarcoma Patients Treated with Immune Checkpoint Inhibitors: A Case Series of Seven Patients from a Single Institution. Florou, et al.


April 4, 2018

Toxicological and Pharmacological Assessment of AGEN1884, a Novel Human IgG1 anti-CTLA-4 Antibody. Gombos, et al.

European Society for Medical Oncology (ESMO)

October 19-23, 2018

Phase 1/2 Study of CTLA-4 Inhibitor AGEN1884 + PD-1 Inhibitor AGEN2034 in Patients With Advanced/Refractory Solid Tumors, With Expansion Into Second-Line Cervical Cancer and Solid Tumors. Coward, et al.

American Society of Clinical Oncology (ASCO)

June 1-5, 2018

Phase One Open-Label, Ascending Dose Trial of AGEN1884, an Anti-CTLA-4 Monoclonal Antibody, in Advanced Solid Malignancies: Dose Selection for Combination with PD-1 Blockade. Wilky, et al.

American Association for Cancer Research (AACR)

April 14-18, 2018

Evaluation of Peripheral T Cell Subset Proliferation as a Pharmacodynamic Assay to Guide the Development of Anti-CTLA-4 and PD-1 Antibody Combinations in Patients With Solid Tumors. de Souza, et al.

Society for Immunotherapy of Cancer (SITC)

November 9-12, 2017

Characterization of the anti-CTLA-4 Antibody AGEN1884, Including Toxicology and Pharmacology Assessments in Non-human Primates. Gombos, et al.

American Society of Clinical Oncology (ASCO)

June 2-6, 2017

Phase 1, Open-Label, Multiple-Ascending-Dose Trial of AGEN1884, an Anti–CTLA-4 Monoclonal Antibody, in Advanced Solid Malignancies. Wilky, et al.

American Association for Cancer Research (AACR)

April 1-5, 2017

AGEN1884, an IgG1 anti-CTLA-4 Antibody, Combines Effectively with PD-1 Blockade in Primary Human T Cell Assays and in a Non-human Primate Pharmacodynamic (PD) Model. Drouin, et al.

American Association for Cancer Research (AACR)

April 16-20, 2016

AGEN1884 and AGEN2041: Two Functionally Distinct anti-CTLA-4 Antagonist Antibodies. Drouin, et al.