Investigational Drug
Balstilimab
TrialFetch AI Analysis
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Overview
Balstilimab (AGEN2034; BAL) is an investigational, fully human IgG4 monoclonal antibody targeting programmed cell death protein 1 (PD-1). It has been studied as monotherapy and in combinations—particularly with the CTLA-4 inhibitors zalifrelimab and botensilimab—in cervical, colorectal and other solid tumors. It is not FDA-approved; a biologics license application for recurrent/metastatic cervical cancer was voluntarily withdrawn in 2021 after the FDA recommended against pursuing accelerated approval following full approval of pembrolizumab in the same setting. (investor.agenusbio.com)
Mechanism of action
Balstilimab binds PD-1 and blocks its interaction with PD-L1 and PD-L2, preventing inhibitory PD-1 signaling and potentially restoring cytotoxic T-cell activity against tumors. (cancer.gov)
Efficacy
Cervical cancer monotherapy: In a single-arm phase I/II study, 140 efficacy-evaluable patients with previously treated recurrent or metastatic cervical cancer received balstilimab 3 mg/kg every two weeks. The confirmed objective response rate (ORR) was 15.0% (95% CI, 10.0–21.8%), including 3.6% complete responses and 11.4% partial responses. The disease-control rate was 49.3%, and median response duration was 15.4 months. ORR was 20.0% in PD-L1-positive and 7.9% in PD-L1-negative disease. (pmc.ncbi.nlm.nih.gov)
Randomized cervical-cancer study: In the phase II RaPiDS trial, investigator-assessed ORR was 24% with balstilimab–zalifrelimab and 15% with balstilimab–placebo; blinded independent review found ORRs of 24% and 26%, respectively. Because the study was non-comparative and the investigator and independent assessments differed, it did not establish that adding zalifrelimab improved efficacy. (annalsofoncology.org)
Colorectal cancer combination: In a peer-reviewed phase I study of 101 response-evaluable patients with heavily pretreated, microsatellite-stable metastatic colorectal cancer, botensilimab plus balstilimab produced a 17% ORR (95% CI, 10–26%) and 61% disease-control rate. Median response duration was not reached and median progression-free survival was 3.5 months. These results apply to the combination and do not isolate balstilimab’s contribution. (pubmed.ncbi.nlm.nih.gov)
Safety
With cervical-cancer monotherapy, 71.4% of patients experienced treatment-related adverse events; commonly reported events included asthenia and diarrhea. The most frequent grade ≥3 treatment-related events were immune-mediated enterocolitis (3.1%) and diarrhea (1.9%). (pmc.ncbi.nlm.nih.gov)
In RaPiDS, treatment-related adverse events occurred in 71% of patients receiving balstilimab–zalifrelimab and 64% receiving balstilimab–placebo; grade 3 events occurred in 23% and 15%, respectively. No treatment-related deaths were reported. (annalsofoncology.org)
With botensilimab–balstilimab in metastatic colorectal cancer, 89% experienced treatment-related adverse events, most commonly fatigue (35%), diarrhea (32%) and fever (24%). Twelve percent discontinued because of treatment-related toxicity, and no grade 5 treatment-related events occurred. (pubmed.ncbi.nlm.nih.gov)
Further reading
- Balstilimab monotherapy in recurrent/metastatic cervical cancer — Gynecologic Oncology
- Balstilimab plus zalifrelimab in advanced cervical cancer — Journal of Clinical Oncology
- Botensilimab plus balstilimab in microsatellite-stable metastatic colorectal cancer — Nature Medicine
- NCI Drug Dictionary: balstilimab
Last updated: Sep 2026
Active trials using Balstilimab
Found 7 active trials using this drug:
TrialFetch AI summary: Adults with chemorefractory MSS/pMMR metastatic colorectal cancer, 1–5 liver lesions suitable for SBRT, and at least one measurable unirradiated extrahepatic lesion receive liver-directed SBRT plus botensilimab (an Fc-engineered anti-CTLA-4 antibody) and balstilimab (an anti-PD-1 antibody).
ClinicalTrials.gov ID: NCT07128355
TrialFetch AI summary: Adults with microsatellite-stable metastatic pancreatic ductal adenocarcinoma that has progressed after at least one systemic therapy receive SBRT followed by botensilimab, an investigational Fc-engineered anti-CTLA-4 antibody, plus balstilimab, an investigational anti-PD-1 antibody. Eligible patients must have ECOG 0–1 and a previously unirradiated, biopsy-accessible lesion.
ClinicalTrials.gov ID: NCT06843551
TrialFetch AI summary: Adults with measurable, microsatellite-stable, KRAS-mutant metastatic colorectal cancer who have progressed on, cannot tolerate, or cannot receive fluoropyrimidine, oxaliplatin, and irinotecan receive botensilimab (an Fc-engineered anti-CTLA-4 antibody) plus balstilimab (an anti-PD-1 antibody), high-dose IV vitamin C, and a fasting-mimicking diet. Prior anti-PD-1 or anti-CTLA-4 therapy and current diabetes are exclusions.
ClinicalTrials.gov ID: NCT06336902
TrialFetch AI summary: Patients with locally advanced or metastatic castration-resistant prostate cancer, pancreatic cancer, or HPV-negative head and neck squamous cell carcinoma who have no beneficial standard treatment option receive evofosfamide plus zalifrelimab and balstilimab. Evofosfamide releases a DNA-crosslinking agent in hypoxic tumor tissue; zalifrelimab blocks CTLA-4 and balstilimab blocks PD-1.
ClinicalTrials.gov ID: NCT06782555
TrialFetch AI summary: Adults with unresectable or metastatic mismatch repair–proficient colorectal cancer or pancreatic ductal adenocarcinoma (PDAC) and a vaccine-covered KRAS mutation receive a mutant KRAS long-peptide vaccine with poly-ICLC, plus balstilimab (anti-PD-1) and botensilimab (Fc-engineered anti-CTLA-4). Cohorts include patients after 4–6 months of first-line chemotherapy and a PDAC cohort allowing up to three prior regimens, including a KRAS inhibitor.
ClinicalTrials.gov ID: NCT06411691
TrialFetch AI summary: Adults with unresectable or metastatic esophageal, gastric, or gastroesophageal junction adenocarcinoma after one prior metastatic treatment line, or recurrence during or within six months of perioperative therapy, receive ramucirumab plus paclitaxel with investigational agenT-797 (CD1d-directed invariant natural killer T cells), botensilimab (Fc-enhanced anti-CTLA-4), and balstilimab (anti-PD-1).
ClinicalTrials.gov ID: NCT06251973
TrialFetch AI summary: Adults with newly diagnosed IDH-wild-type, MGMT-promoter-unmethylated glioblastoma who have completed radiotherapy, with or without temozolomide, receive implanted SonoCloud-9 ultrasound-mediated blood–brain barrier opening with liposomal doxorubicin and two investigational checkpoint antibodies: balstilimab (anti-PD-1) and botensilimab (Fc-engineered anti-CTLA-4).
ClinicalTrials.gov ID: NCT05864534
