Botensilimab + Balstilimab for Colorectal Cancer
(BBOpCo Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Nicholas DeVito, MD
Must not be taking: Corticosteroids, Immunosuppressants, Live vaccines, others
Disqualifiers: Liver metastases, Autoimmune disease, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a single-arm, interventional, pilot clinical trial. Fifteen evaluable patients will have tumor-informed ctDNA testing at baseline and start botensilimab and balstilimab treatment. They will receive botensilimab and balstilimab in 6-week cycles until progression, after which mFOLFOX6 and bevacizumab or panitumumab will be added to the regimen. Subjects will have safety testing at baseline and every two weeks while on study drug. Study treatment with botensilimab and balstilimab, mFOLFOX6, and bevacizumab or panitumumab will be continued until radiographic or clinical progression, toxicity, or patient withdrawal. Subjects will have one safety follow up visit 30 days after the last treatment and will be followed for survival every 12 weeks for up to 2 years.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, if you are using medications that are prohibited in combination with the study drug, you may need to stop those. It's best to discuss your current medications with the trial team to see if any adjustments are needed.
What data supports the idea that Botensilimab + Balstilimab for Colorectal Cancer is an effective treatment?
The available research does not provide specific data on the effectiveness of Botensilimab + Balstilimab for Colorectal Cancer. Instead, it focuses on other treatments and their outcomes for this condition. Without direct evidence from studies on Botensilimab + Balstilimab, we cannot conclude its effectiveness compared to other treatments.
12345What safety data exists for Botensilimab and Balstilimab in humans?
Immune checkpoint inhibitors like Balstilimab (anti-PD-1) and Botensilimab (anti-CTLA-4) can cause side effects such as diarrhea and colitis (inflammation of the colon). These side effects are more common with CTLA-4 inhibitors, and combination therapies may increase the risk of these issues.
678910What makes the drug Botensilimab + Balstilimab unique for colorectal cancer?
The combination of Botensilimab and Balstilimab is unique because it involves two immune checkpoint inhibitors that may work together to enhance the body's immune response against colorectal cancer, offering a novel approach compared to traditional chemotherapy or targeted therapies.
311121314Eligibility Criteria
This trial is for patients with colorectal cancer. Participants must have tumor-informed ctDNA testing at baseline to start treatment. The study excludes certain individuals, but specific exclusion criteria are not provided.Inclusion Criteria
The participant (or legally acceptable representative if applicable) provides written informed consent for the trial
I have not had any drug treatments for colon cancer.
I may have had chemotherapy before or after surgery with the study leader's approval.
+11 more
Exclusion Criteria
I have had a blockage in my intestines in the last 3 months.
A WOCBP who is pregnant or breastfeeding or has a positive pregnancy test within 72 hours prior to receiving study treatment
I haven't had any cancer except for certain treated types in the past 2 years.
+16 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
4 weeks
1 visit (in-person)
Treatment
Participants receive botensilimab and balstilimab in 6-week cycles until progression, with mFOLFOX6 and bevacizumab or panitumumab added upon progression.
Up to 2 years
Visits every 2 weeks (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment, with a safety follow-up visit 30 days after the last treatment and survival follow-up every 12 weeks for up to 2 years.
Up to 2 years
1 visit (in-person) at 30 days, then phone calls every 12 weeks
Participant Groups
The BBOpCo trial tests botensilimab and balstilimab treatments in cycles until the disease progresses. If progression occurs, mFOLFOX6 chemotherapy with bevacizumab or panitumumab is added. Safety is monitored every two weeks during treatment.
1Treatment groups
Experimental Treatment
Group I: TreatmentExperimental Treatment7 Interventions
botensilimab + balstilimab until disease progression, then botensilimab + balstilimab + mFOLFOX6 (leucovorin, fluorouracil, oxaliplatin) + {bevacizumab or panitumumab}
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Duke UniversityDurham, NC
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Who Is Running the Clinical Trial?
Nicholas DeVito, MDLead Sponsor
Gateway for Cancer ResearchCollaborator
Agenus Inc.Industry Sponsor
References
Impact of Subsequent Therapies on Outcome of the FIRE-3/AIO KRK0306 Trial: First-Line Therapy With FOLFIRI Plus Cetuximab or Bevacizumab in Patients With KRAS Wild-Type Tumors in Metastatic Colorectal Cancer. [2022]We investigated choice and efficacy of subsequent treatment, with special focus on second-line therapy, in the FIRE-3 trial (FOLFIRI plus cetuximab [arm A] or bevacizumab [arm B]) for patients with KRAS wild-type metastatic colorectal cancer.
Dual Inhibition of EGFR and VEGF in Heavily Pretreated Patients with Metastatic Colorectal Cancer. [2018]The aim of this study was to evaluate the efficacy and safety of combining irinotecan, bevacizumab, and cetuximab/panitumumab as a 4th-line treatment in patients with metastatic colorectal cancer.
Single-Agent Panitumumab in Frail Elderly Patients With Advanced RAS and BRAF Wild-Type Colorectal Cancer: Challenging Drug Label to Light Up New Hope. [2022]No prospective trials have specifically addressed the efficacy and safety of panitumumab in elderly patients with metastatic colorectal cancer (CRC). We aimed at assessing the efficacy and safety of single agent panitumumab in "frail" elderly patients diagnosed with metastatic RAS and BRAF wild-type CRC.
Metastatic Colorectal Cancer Outcomes by Age Among ARCAD First- and Second-Line Clinical Trials. [2022]We evaluated the time to progression (TTP) and survival outcomes of second-line therapy for metastatic colorectal cancer among adults aged 70 years and older compared with younger adults following progression on first-line clinical trials.
A phase II trial of gefitinib in combination with capecitabine and oxaliplatin as first-line chemotherapy in patients with advanced colorectal cancer. [2018]This study was designed as a multicentre phase II trial to assess the efficacy and safety of gefitinib in association with capecitabine and oxaliplatin in patients with untreated metastatic colorectal cancer.
Management of Gastro-Intestinal Toxicity of the Pi3 Kinase Inhibitor: Optimizing Future Dosing Strategies. [2023]The phosphatidylinositol 3-kinase (PI3K) pathway plays a key role in cancer progression and in host immunity. Idelalisib was the first of this class to be approved with the second-generation Pi3 kinase inhibitors copanlisib, duvelisib and umbralisib, subsequently being approved in the United States. Real-world data are lacking, however, in relation to the incidence and toxicity of Pi3 kinase inhibitor-induced colitis. We here review, in the first instance, the general landscape of the Pi3K inhibitors in the context of hematological malignancies, with a focus on the adverse gastrointestinal side effects reported by various clinical trials. We further review the available worldwide pharmacovigilance data in relation to these drugs. Finally, we describe our own real-world experience with idelalisib-induced colitis management in our center and in a national setting.
Impact of age on the toxicity of immune checkpoint inhibition. [2023]Indications for immune checkpoint inhibitor therapy are increasing. As the population ages, many patients receiving such drugs will be older adults. Such patients are under-represented in clinical trials, and therefore the safety of immune checkpoint inhibitors in this population has not been adequately assessed. A retrospective multicenter analysis of toxicities was performed in patients with advanced or metastatic solid cancers receiving anti-programmed cell death protein 1 (anti-PD-1) and/or anti-CTLA4 antibodies across three age cohorts (
The Risk of Diarrhea and Colitis in Patients With Advanced Melanoma Undergoing Immune Checkpoint Inhibitor Therapy: A Systematic Review and Meta-Analysis. [2019]Checkpoint inhibitors are a first-line therapy for advanced melanoma, though their use is limited by diarrhea and colitis. The aim of our study was to determine the risk of these toxicities associated with immunotherapy in advanced melanoma. Electronic databases were searched through June 2017 for prospective studies reporting the risk of diarrhea and colitis in advanced melanoma treated with anti-programmed death-1 (PD-1) or anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors. Standardized definitions assessed the grade of diarrhea and colitis. Pooled incidence and weighted relative risk estimates with 95% confidence intervals (CI) were estimated using random effects model. Eighteen studies were included: 6 studies (1537 patients) with PD-1 inhibitors and 15 studies (3116 patients) with CTLA-4 inhibitors. The incidence of all-grade diarrhea was 13.7% (95% CI, 10.1%-17.2%) for anti-PD-1 and 35.4% (95% CI, 30.4%-40.5%) for anti-CTLA-4. The incidence of all-grade colitis was 1.6% (95% CI, 0.7%-2.4%) for anti-PD-1, and 8.8% (95% CI, 6.1%-11.5%) for anti-CTLA-4. When PD-1 inhibitors were compared directly with CTLA-4 inhibitors, the relative risk of all-grade diarrhea was 0.58 (95% CI, 0.43-0.77), and the relative risk of all-grade colitis was 0.16 (95% CI, 0.05-0.51). The rate of therapy discontinuation was numerically higher for anti-CTLA-4 therapy compared with anti-PD-1 therapy. Finally, 2 studies compared combination immunotherapy with anti-CTLA-4 therapy alone. The relative risk of developing all-grade diarrhea and colitis with combination therapy was 1.31 (95% CI, 1.09-1.57) and 1.21 (95% CI, 0.73-1.99), respectively. Diarrhea and colitis are frequent toxicities associated with checkpoint inhibitors, and seem to be most common with CTLA-4 inhibitors.
FDA Approval Summary: Pembrolizumab for the First-line Treatment of Patients with MSI-H/dMMR Advanced Unresectable or Metastatic Colorectal Carcinoma. [2022]The FDA approved pembrolizumab on June 29, 2020, for the treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) colorectal cancer with no prior systemic treatment for advanced disease. The approval was based on data from Study Keynote-177, which randomly allocated patients to receive either pembrolizumab or standard of care (SOC) with chemotherapy. Overall survival (OS) and independently assessed progression-free survival (PFS) were the primary endpoints. At the time of the final PFS analysis and second prespecified interim OS analysis, the estimated median PFS was 16.5 months (95% CI: 5.4-32.4) versus 8.2 months (95% CI: 6.1-10.2) in the pembrolizumab and SOC arms, respectively [HR: 0.60 (95% CI: 0.45-0.80); two-sided P = 0.0004]. FDA assessed unblinded OS data during the review of the application and identified no safety concerns that would preclude approval of this supplement. Adverse reactions occurring in >30% of patients receiving pembrolizumab were diarrhea, fatigue/asthenia, and nausea. Adverse reactions occurring in >30% of patients receiving SOC were diarrhea, nausea, fatigue/asthenia, neutropenia, decreased appetite, peripheral neuropathy (high-level term), vomiting, abdominal pain, constipation, and stomatitis. Duration of treatment in the pembrolizumab arm was almost double (median 11.1 months, range 0-30.6 months) than the duration of treatment in patients receiving SOC (median, 5.7 months). Approval of pembrolizumab is likely to change the treatment paradigm for first-line treatment with MSI-H advanced colorectal cancer given the study results and different safety profile.
Association of immune-checkpoint inhibitors and the risk of immune-related colitis among elderly patients with advanced melanoma: real-world evidence from the SEER-Medicare database. [2022]The use of anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) therapy (ipilimumab) and anti-programmed cell-death 1 (anti-PD1) agents (nivolumab and pembrolizumab) in advanced melanoma have been associated with immune-related adverse events (irAEs) including colitis. We aimed to estimate the incidence and the risk of colitis in elderly patients with advanced melanoma treated with anti-CTLA4 and anti-PD1 in the real-world setting.
Phase II trial of T138067, a novel microtubule inhibitor, in patients with metastatic, refractory colorectal carcinoma. [2018]This study was conducted before the approval of oxaliplatin, cetuximab, and bevacizumab and was designed to evaluate a novel microtubule targeting agent, T138067, in patients with metastatic colorectal cancer (CRC) previously treated with irinotecan and 5-fluorouracil.
Biweekly cetuximab in combination with FOLFOX-4 in the first-line treatment of wild-type KRAS metastatic colorectal cancer: final results of a phase II, open-label, clinical trial (OPTIMIX-ACROSS Study). [2023]This phase II study aims to evaluate the efficacy and safety of biweekly cetuximab in combination with oxaliplatin, leucovorin, and fluorouracil (FOLFOX-4) as first-line treatment of metastatic wild-type KRAS colorectal cancer.
A Phase Ib Dose-Escalation Study of Encorafenib and Cetuximab with or without Alpelisib in Metastatic BRAF-Mutant Colorectal Cancer. [2022]Preclinical evidence suggests that concomitant BRAF and EGFR inhibition leads to sustained suppression of MAPK signaling and suppressed tumor growth in BRAFV600E colorectal cancer models. Patients with refractory BRAFV600-mutant metastatic CRC (mCRC) were treated with a selective RAF kinase inhibitor (encorafenib) plus a monoclonal antibody targeting EGFR (cetuximab), with (n = 28) or without (n = 26) a PI3Kα inhibitor (alpelisib). The primary objective was to determine the maximum tolerated dose (MTD) or a recommended phase II dose. Dose-limiting toxicities were reported in 3 patients receiving dual treatment and 2 patients receiving triple treatment. The MTD was not reached for either group and the phase II doses were selected as 200 mg encorafenib (both groups) and 300 mg alpelisib. Combinations of cetuximab and encorafenib showed promising clinical activity and tolerability in patients with BRAF-mutant mCRC; confirmed overall response rates of 19% and 18% were observed and median progression-free survival was 3.7 and 4.2 months for the dual- and triple-therapy groups, respectively.Significance: Herein, we demonstrate that dual- (encorafenib plus cetuximab) and triple- (encorafenib plus cetuximab and alpelisib) combination treatments are tolerable and provide promising clinical activity in the difficult-to-treat patient population with BRAF-mutant mCRC. Cancer Discov; 7(6); 610-9. ©2017 AACR.See related commentary by Sundar et al., p. 558This article is highlighted in the In This Issue feature, p. 539.
Adagrasib Data Create Buzz at ESMO. [2022]In phase I/II KRYSTAL-1 trial, the KRASG12C inhibitor adagrasib demonstrated encouraging clinical activity against metastatic colorectal cancer, both as a monotherapy and when combined with the EGFR inhibitor cetuximab. In patients who received adagrasib alone, the disease control rate was 87% and progression-free survival was 5.6 months. Among patients who received the drug combination, the disease control rate was 100%; data on progression-free survival were immature. The findings, along with data on the KRASG12C inhibitor sotorasib, were presented at the 2021 European Society for Medical Oncology Congress.