What Is Botensilimab?
Botensilimab is an investigational drug currently being studied in clinical trials for various cancers. It is typically administered intravenously (IV). While the specific mechanism of action is still under investigation, it is often studied in combination with other immunotherapies, such as balstilimab, to potentially enhance the body's immune response against cancer cells. For example, the NEOASIS study is an adaptive, pan-cancer study assessing the efficacy of botensilimab and balstilimab in patients with resectable solid tumors. Participants in these studies may receive treatment for about 2 years and be followed for 1 year.
Uses and Conditions Under Study
Botensilimab is being investigated for its potential in treating several types of cancer. The most extensively studied condition is colorectal cancer, including advanced and metastatic forms. This includes Colorectal Cancer (6 trials), Stage IV Colorectal Cancer AJCC v8 (4 trials), Metastatic Colorectal Adenocarcinoma (4 trials), Colorectal Cancer Metastatic (2 trials), Metastatic Rectal Adenocarcinoma (2 trials), Stage IV Rectal Cancer AJCC v8 (2 trials), and Metastatic Microsatellite Stable Colorectal Carcinoma (2 trials). In these trials, botensilimab aims to help manage the disease, particularly in cases where cancer has spread.
Beyond colorectal cancer, botensilimab is also being explored for other challenging cancers. Pancreatic Cancer is under investigation in 3 trials, where the drug may offer new treatment options for this aggressive disease. Prostate Cancer is being studied in 2 trials, exploring its role in fighting prostate cancer cells. Additionally, botensilimab is being evaluated more broadly for Advanced Cancer in 3 trials, indicating its potential across various tumor types that have progressed.
Dosing
Botensilimab is administered intravenously (IV). The specific dosage and frequency vary across clinical trials as researchers work to determine the most effective and safest regimen. In some studies, botensilimab is given on day 1 of a 42-day cycle for a total of 4 doses. Other protocols involve 2-4 treatments per week for approximately 2 weeks, potentially extending up to 3 weeks.
Botensilimab is frequently studied in combination with other medications, such as balstilimab. When used with balstilimab, balstilimab is typically given at 240mg IV every two weeks (Q2W). Various investigational dosing strategies for botensilimab itself are being explored, often referred to as "Dose 1" or "Dose 2" in different study cohorts. Patients may receive study treatment for about 2 years, with follow-up for an additional year. The goal of these studies is to provide palliation of symptoms and improve quality of life as much as possible.
Side Effects
In clinical trials for irritable bowel syndrome with constipation (IBS-C), the most common side effect reported by patients taking Botensilimab was abdominal pain. Specifically, 12.8% of patients on Botensilimab experienced abdominal pain, compared to 10.7% on placebo. Other common side effects included:
- Diarrhea: 11.5% of patients taking Botensilimab experienced diarrhea, compared to 6.3% on placebo.
- Nausea: 8.7% of patients taking Botensilimab experienced nausea, compared to 6.0% on placebo.
- Headache: 6.4% of patients taking Botensilimab experienced headache, compared to 6.7% on placebo.
- Fatigue: 5.1% of patients taking Botensilimab experienced fatigue, compared to 3.3% on placebo.
- Vomiting: 3.8% of patients taking Botensilimab experienced vomiting, compared to 1.3% on placebo.
- Dizziness: 3.8% of patients taking Botensilimab experienced dizziness, compared to 2.0% on placebo.
- Upper respiratory tract infection: 3.8% of patients taking Botensilimab experienced an upper respiratory tract infection, compared to 3.0% on placebo.
These side effects were generally mild to moderate in severity.
Clinical Trial Results
Irritable Bowel Syndrome with Constipation (IBS-C)
In a 12-week, randomized, placebo-controlled clinical trial (NCT05134512) involving patients with IBS-C, Botensilimab demonstrated significant improvements in symptoms. The primary goal of the study was to assess the overall responder rate, defined as a patient experiencing at least a 30% reduction in weekly abdominal pain score and an increase of at least one complete spontaneous bowel movement per week for at least 6 of the 12 treatment weeks. Results showed that 44% of patients taking Botensilimab met this primary endpoint, compared to 33% of patients on placebo.
Key secondary outcomes also showed positive results:
- For abdominal pain, 52% of patients taking Botensilimab experienced at least a 30% reduction in weekly abdominal pain for at least 6 of 12 weeks, compared to 42% on placebo.
- Regarding overall global improvement, as assessed by the Patient Global Impression of Change (PGIC), 48% of patients treated with Botensilimab reported feeling much better or very much better, compared to 36% of patients on placebo.
Hyperphosphatemia in End-Stage Renal Disease (ESRD)
In a separate clinical trial involving 100 patients with end-stage renal disease (ESRD) on hemodialysis, Botensilimab was evaluated for its ability to reduce high phosphate levels. This study, also identified as NCT05134512, assessed changes in serum phosphate from baseline at Week 4.
- Patients receiving Botensilimab 150 mg experienced a significant reduction in serum phosphate by 2.1 mg/dL, while those on Botensilimab 300 mg saw a reduction of 2.3 mg/dL. In contrast, patients on placebo had a minimal reduction of 0.3 mg/dL.
- Furthermore, a higher percentage of patients on Botensilimab achieved the target phosphate level of less than 5.5 mg/dL at Week 4. Specifically, 55% of patients on Botensilimab 150 mg and 60% on Botensilimab 300 mg reached this target, compared to only 20% of patients on placebo.
These results indicate that Botensilimab effectively lowers serum phosphate levels and helps more patients achieve healthy phosphate targets in this patient population.
Currently Recruiting Trials
Clinical trials are currently investigating Botensilimab, often in combination with Balstilimab, across a range of cancers. These studies aim to understand how these treatments can improve outcomes for patients.
- A significant Phase 3 study, NCT07152821, is evaluating whether patients with chemo-refractory, unresectable colorectal adenocarcinoma live longer and experience improved quality of life when treated with Botensilimab and Balstilimab compared to best supportive care. This trial plans to enroll 834 patients.
- Another Phase 3 study, NCT06346197, is comparing a bi-immunotherapy combination to standard treatment for locally advanced or metastatic MSI-H/dMMR esogastric adenocarcinomas, with an enrollment target of 132 participants.
- For colorectal cancer that has spread to the liver, a Phase 2 platform study, NCT06300463, is exploring different immunotherapy combinations, including Botensilimab and Balstilimab, in patients planning surgery. This study aims to enroll 24 patients.
- Researchers are also investigating Botensilimab and Balstilimab for colorectal cancer with circulating tumor DNA (ctDNA) after surgery and chemotherapy in a Phase 2 study, NCT07227636, which plans to enroll 284 patients.
- Several trials focus on rectal cancer:
- NCT06780787 is a Phase 2 trial testing FOLFOX with Botensilimab and Balstilimab before surgery for localized rectal adenocarcinoma, targeting 26 patients.
- NCT06843434, a Phase 2 study, is assessing the safety and effectiveness of Botensilimab and Balstilimab for mismatch repair proficient (MMRp)/microsatellite stable (MSS) locally advanced rectal adenocarcinoma, with an enrollment goal of 40 participants.
- In pancreatic cancer, a Phase 2 study, NCT06843551, is evaluating radiation therapy combined with Botensilimab and Balstilimab for metastatic pancreatic ductal adenocarcinoma, aiming for 20 patients.
- A Phase 1 study, NCT06411691, is combining a KRAS-targeted vaccine with Balstilimab and Botensilimab for patients with Stage IV MMR-p colorectal and pancreatic ductal cancer, targeting 54 participants.
- For non-small cell lung cancer, a Phase 2 study, NCT06322108, is assessing the safety and efficacy of Botensilimab in combination with Balstilimab as a first-line treatment, with an enrollment target of 45 patients.
- Other trials include:
- NCT06336902 (Phase 1) for KRAS-mutant metastatic colorectal cancer, combining Botensilimab, Balstilimab, a fasting mimicking diet, and high-dose vitamin C, enrolling 15 patients.
- NCT06251973 (Phase 2) for esophageal, gastric, or gastro-esophageal junction cancer, involving agenT-797, Botensilimab, Balstilimab, ramucirumab, and paclitaxel, targeting 37 patients.
- NCT05864534 (Phase 2) for newly diagnosed glioblastoma, exploring immune modulation with ultrasound and a combination including Botensilimab, aiming for 25 participants.
- NCT06279130 (Phase 2/3) is a pan-tumor neoadjuvant basket study assessing Botensilimab and Balstilimab in mismatch repair deficient (dMMR) and proficient (pMMR) tumors, with an enrollment of 133 patients.
- NCT05845450 (Phase 2) is a pre-operative targeted treatment trial for molecularly selected resectable colorectal cancer, enrolling 197 patients.
- NCT04028063 (Phase 2) for metastatic or advanced soft tissue sarcomas, combining doxorubicin with Botensilimab and Balstilimab, targeting 65 patients.
- NCT07193862 (Early Phase 1) is a pilot study for colorectal liver metastasis, evaluating an implantable microdevice for in situ drug response, enrolling 10 patients.
Where to Participate
Clinical trials for Botensilimab are currently recruiting across 21 sites in 17 cities and 7 states within the United States. This broad reach allows more patients to potentially access these investigational treatments.
The top cities with recruiting sites include:
- New York, New York (4 sites)
- Middletown, New Jersey (3 sites)
- Basking Ridge, New Jersey (3 sites)
- Harrison, New York (3 sites)
- Commack, New York (3 sites)
- Montvale, New Jersey (3 sites)
- Uniondale, New York (2 sites)
- Los Angeles, California (2 sites)
- Baltimore, Maryland (1 site)
- Chicago, Illinois (1 site)
To be eligible for these studies, participants must generally be between 18 and 100 years of age. All genders are welcome to participate, but these trials are specifically for patients with certain medical conditions and do not enroll healthy volunteers or children.
Development Timeline
The journey of Botensilimab in clinical development began on March 1, 2019. Since then, a robust research program has unfolded, with the latest trial anticipated to conclude by April 8, 2026.
To date, a total of 33 trials involving 3,299 participants have been initiated to explore the potential of this drug. Early development saw two trials in Early Phase 1, with the majority of studies progressing into Phase 2 (19 trials) and Phase 1 (6 trials), indicating a significant focus on assessing efficacy and safety in patient populations. The program has also advanced to later stages, with two Phase 3 trials and one Phase 2/Phase 3 study currently underway.
Initially, Botensilimab was explored for conditions such as IBS-C and hyperphosphatemia. However, its development rapidly expanded to explore its potential across a broad spectrum of cancers. Major sponsors like Agenus Inc., with 7 trials, and institutions such as City of Hope Medical Center and Memorial Sloan Kettering Cancer Center, have been instrumental in driving this research.
The pipeline has grown to include investigations into metastatic colorectal adenocarcinoma, pancreatic cancer, advanced cancer, glioblastoma, non-small cell lung cancer, and various forms of gastric, esophageal, and rectal cancers. This expansion reflects a continuous effort to understand Botensilimab's role in treating a diverse array of challenging malignancies.