Botensilimab + Balstilimab vs Best Supportive Care as Therapy in Chemo-refractory, Unresectable, Colorectal Adenocarcinoma: The BATTMAN Trial

Plain English Summary

Botensilimab + Balstilimab vs Best Supportive Care as Therapy in Chemo-refractory, Unresectable, Colorectal Adenocarcinoma is a Phase 3 clinical trial sponsored by Canadian Cancer Trials Group studying Colorectal Cancer. This trial tests if a combination of two immunotherapy drugs, botensilimab and balstilimab, can help patients with advanced colorectal cancer live longer compared to standard supportive care. It is for patients with colorectal cancer that has spread and cannot be removed by surgery, and who have not responded to previous treatments. Participation involves receiving either the new drug combination or best supportive care, with regular check-ups and tests. The main alternative for eligible patients is best supportive care, which focuses on managing symptoms and improving quality of life. The trial aims to enroll 834 participants.

Official Summary

This study is being done to answer the main question of: Do patients with colorectal cancer that cannot be removed by surgery, that is treated with two new immunotherapy drugs, botensilimab and balstilimab, live longer? Other important questions include: Is their quality of life better? Do their tumours slow in growth or possibly shrink in size? Are there markers in their tumour or blood that can predict whether they achieve any of these benefits? In addition, the study is done to confirm the safety of these immunotherapy drugs and to determine how long it takes for the body to metabolize them.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with colorectal cancer that has spread and cannot be surgically removed, and whose cancer has not responded to prior therapies. Must be 18 years or older with a good general health status (ECOG 0 or 1) and a life expectancy of at least 12 weeks. Cannot have active brain or leptomeningeal metastases, a history of organ transplant, or active autoimmune diseases. Must not have received certain prior cancer treatments or immunotherapies within specific timeframes before joining. This trial is studying Colorectal Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how long patients live overall, aiming to see if the new immunotherapy drugs can extend survival compared to standard care. The specific primary outcome measures are: Overall Survival (34 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a critical need for new treatments in patients with advanced colorectal cancer that has become resistant to standard therapies, potentially offering a new option for a difficult-t As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Colorectal Cancer, where improved treatment options are needed.

Investor Insight

This Phase 3 trial for a novel immunotherapy combination in a significant cancer indication suggests a strong belief by the sponsor in the drug's potential, targeting a large patient population with u Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 834 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if your cancer is considered 'chemo-refractory' and 'unresectable', and if you meet the specific eligibility criteria for this trial. Participation involves receiving either the investigational drugs or best supportive care, with regular visits for assessments, scans, and blood tests. You will be asked to complete quality of life questionnaires in English or French. This trial is currently recruiting participants. The trial is being conducted at 12 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 834 participants

Interventions

• OTHER: Best Supportive Care — Measures designed to provide palliation of symptoms and improve quality of life as much as possible
• DRUG: Balstilimab — 450mg IV every 3 weeks
• DRUG: Botensilimab — 75mg IV every 6 weeks x 4 doses

Primary Outcomes

• Overall Survival (34 months)

Secondary Outcomes

• Progression Free Survival (PFS) based on RECIST 1.1 criteria (34 months)
• Overall Response Rate (ORR) based on RECIST 1.1 criteria (34 months)
• Clinical Benefit Rate (CBR) at 6 months based on RECIST 1.1 criteria (34 months)
• Health Related Quality of Life (HRQoL) utilizing EORTC QLQ-C30 (34 months)
• Health Related Quality of Life (HRQoL) utilizing EORTC QLQ-CR29 (34 months)

Full Eligibility Criteria

Inclusion Criteria:

* Must have histologically confirmed colorectal adenocarcinoma that is not deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H).
* Received and failed all prior available therapies, such that the standard of care for the patient would be best supportive care (BSC).
* Must have an Eastern Cooperative Oncology Group (ECOG) performance status 0, or 1.
* Must have presence of measurable or evaluable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST 1.1).
* A life expectancy of ≥ 12 weeks at the time of study entry.
* Must be ≥ 18 years of age.
* Participants must consent to provision of, and investigator must agree to submit, a representative archival formalin fixed paraffin block of tumour tissue for correlative analyses when tumour tissue is available.
* Participants must have adequate organ and marrow function measured within 14 days prior to randomization.
* Participant is able (i.e. sufficiently fluent) and willing to complete the quality of life and health utility questionnaires in either English or French.
* Participant consent must be appropriately obtained in accordance with applicable local and national regulatory requirements.
* Participants must be accessible for treatment and follow-up. Investigators must assure themselves the participants enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
* In accordance with CCTG policy, protocol treatment is to begin within 2 working days of participant enrolment.
* Participants of childbearing potential or partners of participants of childbearing potential must have agreed to use a highly effective contraceptive method

Exclusion Criteria:

* Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen may be eligible for this trial, however, consultation with CCTG in advance of enrolment is required.
* A history of primary immunodeficiency, solid organ transplant or allogeneic bone marrow transplant.
* Current or prior use of immunosuppressive medication within 7 days before the first dose of study drugs, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease that has required systemic treatment within 2 years of the start of study drug.
* Active or uncontrolled intercurrent illness.
* Active brain metastases or leptomeningeal metastases.
* Receipt of live attenuated vaccination administered within 30 days prior to randomization.
* Lactating women who choose to breast feed.
* Any active disease condition which would render the protocol treatment dangerous or impair the ability of the participant to receive protocol therapy.
* Any condition that does not permit compliance with the protocol.
* Receipt of anti-cancer chemotherapy or biologic therapy within the lesser of i) 21 days, or ii) the usual cycle length of the regimen prior to the first planned dose of study drug.
* Receipt of radiotherapy or investigational agents within four weeks of first planned dose of study drug.
* Any unresolved toxicity (≥ CTCAE grade 2) from previous anti-cancer therapy.
* Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
* History of partial or complete bowel obstruction within the last 3 months prior to study enrolment, signs/symptoms of bowel obstruction or known radiologic evidence of impending obstruction.
* Refractory ascites defined as requiring 2 or more therapeutic paracenteses within the last 4 weeks or ≥ 4 times within the last 3 months or ≥ 1 time within the last 2 weeks or requiring diuretics within 2 weeks prior to study enrolment.
* Active or ongoing diarrhea of CTCAE grade 2 or higher.
* Tumour is mismatch repair deficient (dMMR) or microsatellite instability- high (MSI-H) per a standard local testing method.
* Prior exposure to anti-PD-1/PD-L1/CTLA-4 therapy.

Trial Locations

• BCCA - Prince George, Prince George, British Columbia, Canada
• BCCA - Vancouver, Vancouver, British Columbia, Canada
• Kingston Health Sciences Centre, Kingston, Ontario, Canada
• Lakeridge Health Oshawa, Oshawa, Ontario, Canada
• Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
• Niagara Health System, St. Catharines, Ontario, Canada
• North York General Hospital, Toronto, Ontario, Canada
• Sinai Health System, Toronto, Ontario, Canada
• University Health Network, Toronto, Ontario, Canada
• Centre Integre de Sante et de Services Sociaux, Greenfield Park, Quebec, Canada
• ...and 2 more locations

Frequently Asked Questions

Related Conditions

• Colorectal Cancer
• Adenocarcinoma
• Gastrointestinal Cancers
• Oncology
• Immunotherapy
• Metastatic Cancer
• Cancer Treatment Resistance
• Solid Tumors
• Advanced Cancer
• Chemotherapy-Refractory Cancer

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