balstilimab (AGEN2034) / Agenus, Betta Pharma, Zydus Lifesciences - LARVOL DELTA

Testing the Combination of Anti-Cancer Drugs, Botensilimab (AGEN1181) and Balstilimab (AGEN2034), After Standard Treatment for Colorectal Cancer, Combat Trial (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting | Trial completion date: Sep 2026 ➔ Aug 2029 | Initiation date: Aug 2026 ➔ May 2027 | Trial primary completion date: Sep 2026 ➔ Aug 2029

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor

Neoadjuvant botensilimab plus balstilimab response pattern in locally advanced mismatch repair proficient colorectal cancer. (PubMed, Oncogene) - "Spatial biology analyses (RareCyte Inc.) reveal mechanisms of actions of BOT, a novel innate-adaptive immune activator. These observations have downstream implications for clinical trial designs using neoadjuvant immunotherapy and potentially sparing patients chemotherapy."

Journal • Metastases • Mismatch repair • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Rectal Cancer • Solid Tumor

Results from an expanded phase 1 trial of botensilimab (BOT), a multifunctional anti-CTLA-4, plus balstilimab (BAL; anti-PD-1) for metastatic heavily pretreated microsatellite stable colorectal cancer (MSS CRC) (ESMO-GI 2023) - P1, P2 | "In patients with heavily pretreated metastatic MSS CRC and longer follow-up, the combination of BOT + BAL continues to show durable responses and prolonged overall survival across all subgroups, and a favorable safety profile with no new signals. This study is ongoing, and a randomized global phase 2 trial in MSS CRC patients is actively enrolling (NCT05608044)."

IO biomarker • Late-breaking abstract • Metastases • P1 data • Tumor mutational burden • Colorectal Cancer • Gastrointestinal Cancer • BRAF • KRAS • MSI • NRAS • TMB

Botensilimab, a novel innate/adaptive immune activator, plus balstilimab (anti-PD-1) for metastatic heavily pretreated microsatellite stable colorectal cancer (ESMO-GI 2022) - P1 | "Conclusions BOT + BAL demonstrates unprecedented activity for immunotherapy in heavily pretreated patients with metastatic MSS CRC and manageable safety, consistent with its design. The ORR and DOR, including compelling efficacy in patients without liver metastases, are informing phase 2/3 study designs."

Late-breaking abstract • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Neoadjuvant botensilimab plus balstilimab in resectable mismatch repair proficient and deficient colorectal cancer: NEST-1 clinical trial. (ASCO-GI 2024) - P2 | "BOT/BAL appears to be a safe and active regimen both in pMMR/MSS and dMMR/MSI-H colon as well as rectal cancers. The downstaging observed may spare surgery and/or adjuvant chemotherapy. Given the findings, the study has now expanded to two additional cohorts that are now enrolling to study further the dosing, and timing and/or need for surgery in these patients."

Clinical • Mismatch repair • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MSI

Updated efficacy and safety of botensilimab plus balstilimab in patients with refractory metastatic sarcoma from an expanded phase I study (ESMO 2024) - P1 | "BOT + BAL combination demonstrates durable responses in this diverse poorly immunogenic sarcoma population with longer follow-up and additional pts. Responses in visceral AS are noteworthy, reflecting BOT's differentiated MOA. Trials focusing on AS and other poorly immunogenic sarcomas are planned."

Clinical • Metastases • P1 data • Angiosarcoma • Leiomyosarcoma • Oncology • Sarcoma • Solid Tumor

Neoadjuvant botensilimab (BOT) plus balstilimab (BAL) in resectable mismatch repair proficient (pMMR) and deficient (dMMR) colorectal cancer (CRC): NEST clinical trial update. (ASCO-GI 2025) - P2 | "Neoadjuvant BOT/BAL is safe, with no delays to surgery, and effective. We observed high MPR rates in both MSS and MSI-H CRC with no recurrences to date. The MPR and pCR rate improved with extended time to surgery."

Clinical • Mismatch repair • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Rectal Cancer • Solid Tumor • MSI

Testing the Safety and Feasibility of Immunotherapy Drugs, Botensilimab and Balstilimab, Before Surgery for Clear Cell Renal Cell Carcinoma, NEO RoBOT Trial (clinicaltrials.gov) - P2 | N=16 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting | Trial completion date: Aug 2027 ➔ Dec 2028 | Initiation date: Aug 2026 ➔ May 2027 | Trial primary completion date: Aug 2027 ➔ Dec 2028

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Monitoring botensilimab- and balstilimab-induced T-cell dynamics in refractory mismatch repair proficient metastatic colorectal cancer. (ASCO 2025) - P2 | "In this trial patients were randomized into BOT (75mg or 150mg Q6W, 4x) monotherapy or in combination with BAL (240mg Q2W, for 2 years), versus standard of care (regorafenib or trifluridine/tipiracil). Deep T cell repertoire profiling detected dynamics of circulating T cells with quantitative and qualitative difference related to ICI response. Immune cell tracking from liquid biopsies is a powerful tool to quantify ICI efficacy in real time."

IO biomarker • Metastases • Mismatch repair • pMMR • Colorectal Cancer • Hepatology • Oncology • Solid Tumor

A single-arm, open-label phase 2 trial of doxorubicin plus zalifrelimab, a CTLA-4 inhibitor, with balstilimab, a PD-1 inhibitor, in patients with advanced/metastatic soft tissue sarcomas. (ASCO 2023) - P2 | "Sponsored by Pharmaceutical/Biotech Company, Agenus Bio, Cancer League of Colorado, University of Colorado Cancer Center. Combination DOX/BAL/ZAL led to meaningful efficacy, including favorable PFS6mo and responses in several STS subtypes unlikely to respond to DOX or ICI monotherapy. Further investigation is required to determine if the stage 1 priming dose of ZAL/BAL prior to DOX improved clinical outcomes. An ongoing cohort is exploring a next-generation CTLA-4 inhibitor, botensilimab in combination with DOX +/- BAL."

Clinical • Metastases • P2 data • Angiosarcoma • Fibrosarcoma • Hematological Disorders • Immune Modulation • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Uterine Cancer

Emerging survival plateaus with botensilimab and balstilimab: Pan tumor data from a large phase Ib trial of advanced solid tumors (ESMO 2025) - P1 | "Notably, imAEs / discontinuations correlated with improved survival. These pan tumor late-stage data complement the emerging pan tumor neoadjuvant data, further leveraging the power of BOT + BAL."

Metastases • P1 data • Pan tumor • Colorectal Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor

Botensilimab (Fc-enhanced anti-cytotoxic lymphocyte-association protein-4 antibody) Plus Balstilimab (anti-PD-1 antibody) in Patients With Relapsed/Refractory Metastatic Sarcomas. (PubMed, J Clin Oncol) - P1 | "The combination of BOT/BAL demonstrated promising efficacy and safety in a large cohort of heavily pretreated sarcoma patients. This encouraging activity warrants further investigation (ClinicalTrials.gov identifier: NCT03860272)."

IO biomarker • Journal • Tumor mutational burden • Angiosarcoma • Gastroenterology • Gastrointestinal Disorder • Immunology • Oncology • Sarcoma • Solid Tumor • PD-L1 • TMB

Advanced Renal Cell Cancer Combination Immunotherapy Clinical Trial (ARCITECT; HCRN GU 22-587) (KCRS 2024) - P2 | "Although some patients treated with nivolumab/ipilimumab (Nivo/Ipi) (IO/IO) experience durable responses leading to treatment free intervals, over two-thirds experience disease progression...Combination botensilimab/ balstilimab (Bot/Bal) (anti-CTLA/anti-PD1) has shown impressive anti-tumor activity in diseases where Nivo/Ipi has shown little to no efficacy...Correlative studies will explore immune and molecular predictors of response and resistance to IO/IO in tumor and blood. Clinical trial information: NCT05928806."

Clinical • Metastases • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor

Extended Follow-Up of Botensilimab Plus Balstilimab in an Expanded Cohort of Microsatellite-Stable Metastatic Colorectal Cancer Without Active Liver Metastases. (PubMed, Clin Cancer Res) - "BOT+BAL demonstrated durable responses, long-term survival, and manageable safety in previously-treated MSS mCRC NLM, including in late-line-exposed patients. These results support further evaluation."

Journal • P1 data • Colorectal Cancer • Oncology • Solid Tumor

Botensilimab plus balstilimab in advanced sarcoma: real-world data from a Spanish expanded access program (ESMO 2026) - No abstract available

Clinical • Metastases • Real-world • Real-world evidence • Oncology • Sarcoma • Solid Tumor

Botensilimab, Balstilimab and Regorafenib for the Treatment of Patients With Microsatellite Stable Metastatic Colorectal Cancer Who Have Progressed on Prior Chemotherapy (clinicaltrials.gov) - P1/2 | N=28 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Aug 2026 ➔ Dec 2026 | Trial primary completion date: May 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor • BRAF • PD-L1

A phase I/II study evaluating the safety and efficacy of ivermectin in combination with balstilimab in patients with metastatic triple negative breast cancer. (ASCO 2025) - P1/2 | "The combination of ivermectin and balstilimab is safe and well tolerated. Encouraging CBR was observed in this heavily pretreated population, which warranted continued investigation. Clinical trial information: NCT05318469"

Clinical • Combination therapy • IO biomarker • Metastases • P1/2 data • Anemia • Breast Cancer • Cervical Cancer • Endocrine Disorders • Oncology • Solid Tumor • Triple Negative Breast Cancer

A PHASE IA/IB STUDY OF BOTENSILIMAB, A NOVEL INNATE/ADAPTIVE IMMUNE ACTIVATOR, PLUS BALSTILIMAB FOR THE TREATMENT OF PATIENTS WITH SARCOMA (CTOS 2022) - No abstract available

Clinical • P1 data • Oncology • Sarcoma • Solid Tumor

Advanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587). (ASCO-GU 2024) - P2 | "Although some patients treated with nivolumab/ipilimumab (Nivo/Ipi) (IO/IO) experience durable responses leading to treatment free intervals, over two-thirds experience disease progression...Combination botensilimab/balstilimab (Bot/Bal) (anti-CTLA/anti-PD1) has shown impressive anti-tumor activity in diseases where Nivo/Ipi has shown little to no efficacy...Correlative studies will explore immune and molecular predictors of response and resistance to IO/IO in tumor and blood. Clinical trial information: NCT05928806."

Clinical • Metastases • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Pre-operative Targeted Treatments in Molecularly Selected Resectable Colorectal Cancer (UNICORN) (clinicaltrials.gov) - P2 | N=197 | Recruiting | Sponsor: Gruppo Oncologico del Nord-Ovest | Trial primary completion date: May 2026 ➔ May 2027

Trial primary completion date • Colorectal Cancer • Oncology • Solid Tumor • BRAF

Botensilimab plus balstilimab in microsatellite stable metastatic colorectal cancer: Assessing efficacy in non-liver metastatic sites. (ASCO 2024) - P1, P2 | "In summary, for MSS CRC, BOT and BAL is differentiated from previous I-O combinations by producing deep and durable responses even in difficult-to-treat metastatic sites. In NLM patients, responses were observed in 18–33% of sites of disease including the peritoneum, soft tissue, pleura, and the brain. These compelling results support further investigation in the fully enrolled, randomized, global phase 2 trial in MSS CRC (NCT05608044) and a planned global phase 3 trial."

Clinical • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial. (PubMed, Nat Med) - P1 | "The combination of BOT plus BAL demonstrated a manageable safety profile with no new immune-mediated safety signals and encouraging clinical activity with durable responses. ClinicalTrials.gov identifier: NCT03860272 ."

Journal • Metastases • P1 data • Colorectal Cancer • Fatigue • Gastrointestinal Cancer • Oncology • Solid Tumor • CTLA4

Botensilimab plus balstilimab in an expanded cohort of 123 patients with metastatic microsatellite-stable colorectal cancer and no active liver metastases (ESMO-GI 2025) - P1 | "This is the first presentation of a fully enrolled expanded cohort of pts with MSS mCRC NLM from the phase 1b trial. As of Mar 13, 2025, 123 pts with NLM were enrolled / treated with BOT every 6 wks (62 pts – 1 mg/kg, 61 pts – 2 mg/kg) plus BAL every 2 wks (3 mg/kg). Median age, 56 yrs (range 25–82); median prior lines, 3 (range 1–10); 58% ≥1 metastatic site, 16% treated liver metastases; 16% prior I-O, 30% prior regorafenib, trifluridine/tipiracil ± bevacizumab or fruquitinib; and 67% RAS mutant. BOT / BAL, a novel I-O only combination, demonstrates unprecedented clinical benefit with deep, durable responses, and for the first time, meaningful treatment free survival in refractory MSS mCRC NLM, with a manageable safety profile."

Clinical • IO biomarker • Metastases • Colorectal Cancer • Oncology • Solid Tumor

NEXT GENERATION IMMUNE CHECKPOINT INHIBITION WITH BOTENSILIMAB PLUS BALSTILIMAB IN RECURRENT OVARIAN CANCER: RESULTS BY PLATINUM SENSITIVITY STATUS AND 3-YEAR OVERALL SURVIVAL (IGCS 2026) - P1 | "As of 13 December 2025, 44 patients (n=35 efficacy -evaluable) received BOT+BAL (reverse Kaplan –Meier, 21.3 months [95% CI, 9.2 –33.4]). Median prior lines was 4 (range, 1 –17; 77% had ≥3). No new safety signals occurred."

Checkpoint inhibition • Clinical • Oncology • Ovarian Cancer • Solid Tumor

Botensilimab, a novel innate/adaptive immune activator, plus balstilimab (anti-PD-1) in patients with recurrent platinum refractory/resistant ovarian cancer (SGO 2023) - No abstract available

Clinical • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor