Phase II Study of Adjuvant Botensilimab in Combination With Balstilimab in Patients With Colorectal Cancer and Persistent Circulating Tumor DNA Following Surgery and Chemotherapy
概览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 284
- 试验地点
- 7
- 主要终点
- Rate of ctDNA clearance (Cohort 1a)
概览
简要总结
The researchers are doing this study to find out whether the combination of botensilimab and balstilimab (BOT/BAL), followed by balstilimab alone, is an effective treatment for people with microsatellite stable (MSS) colorectal cancer or colorectal liver metastases (CRLM) who have measurable residual disease (MRD) after standard treatment with surgery and chemotherapy or total neoadjuvant therapy (TNT).
详细描述
This is a 2-part, 2-cohort each. Part-1 will be a non-randomized study of 54 subjects to assess ctDNA clearance, including 2 cohorts. Cohort 1a includes 27 patients with stage III non-MSI-H/pMMR colorectal cancer following surgery and adjuvant chemotherapy or total neoadjuvant therapy (TNT), with persistent MRD. Cohort 1b includes 27 patients with non-MSI-H/pMMR CRLM following surgery and peri-operative chemotherapy, with persistent MRD.
Part-2 will be a randomized, placebo-controlled, double-blind study of 230 patients with non- MSI-H/pMMR CRC with MRD, to assess RFS. Cohort 2a includes 113 patients with stage III non-MSI-H/pMMR colorectal cancer following surgery and adjuvant chemotherapy or TNT with persistent MRD, randomized 2:1 to treatment versus placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject or legally authorized representative, is willing and able to provide written informed consent.
- •Histologically- or cytologically- confirmed colorectal cancer.
- •≥ 18 years of age on day of signing informed consent.
- •Consent for use of archival tissue and blood draws for research purposes.
- •Performance status of ECOG 0 or
- •Known non-MSI-H/pMMR by IHC, PCR or NGS testing. MSKCC confirmation of non-MSI-H/pMMR status is not mandatory prior to enrollment and treatment on the study. For patients with outside testing, if sufficient tissue is available testing may be repeated at MSKCC and will not impact initial eligibility.
- •Consent to undergo MSK IMPACT or NGS, if not previously done
- •Disease specific criteria:
- •Cohorts 1a and 2a: Undergone a complete surgical resection (R0) for stage III colon or rectal cancer, followed by adjuvant chemotherapy with FOLFOX or CAPEOX. Post-operative chemotherapy not required if received previous oxaliplatin-based therapy. Total Neoadjuvant Therapy for rectal cancer with complete clinical and radiographic response is allowed.
- •Cohorts 1b and 2b: Undergone a complete surgical resection (R0) for liver metastasis (ablation or stereotactic body radiation therapy \[SBRT\], but not Y-90, is permitted) and completed standard peri-operative chemotherapy. Peri-operative chemotherapy not required if received previous oxaliplatin-based therapy. Prior floxuridine via Hepatic Arterial Infusion Pump is permitted. Completed definitive treatment for the primary tumor including (R0) resection, or Total Neoadjuvant Therapy for rectal cancer with complete clinical and radiographic response.
排除标准
- •Presence of metastatic or recurrent disease.
- •Known DNA polymerase epsilon (POLE) or DNA polymerase delta (POLD) activating mutation.
- •R1 (microscopic residual tumor) or R2 resection (macroscopic residual tumor at resection margin).
- •Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- •Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- •Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., dexamethasone containing antiemetic regimen or steroids as CT scan contrast premedication) may be enrolled.
- •The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
- •Hypersensitivity to botensilimab or balstilimab or any of its excipients.
- •Chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent
- •a. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
研究组 & 干预措施
Cohort 1b: MSS CRLM (Botensilimab and Balstilimab)
All patients will receive botensilimab IV on day 1 of the 42 day cycle for 4 doses, balstilimab IV on days 1, 15, and 29 of the 42 day cycle. Patient then continues balstilimab alone for an additional two cycles IV on days 1, 15, and 29 of the 42 day cycle.
干预措施: Botensilimab (Drug)
Cohort 1b: MSS CRLM (Botensilimab and Balstilimab)
All patients will receive botensilimab IV on day 1 of the 42 day cycle for 4 doses, balstilimab IV on days 1, 15, and 29 of the 42 day cycle. Patient then continues balstilimab alone for an additional two cycles IV on days 1, 15, and 29 of the 42 day cycle.
干预措施: Balstilimab (Drug)
Cohort 2b: MSS CRLM (Botensilimab and Balstilimab vs. Placebo) Randomized
All patients will receive botensilimab IV on day 1 of the 42 day cycle for 4 doses, balstilimab IV on days 1, 15, and 29 of the 42 day cycle. Patient then continues balstilimab alone for an additional two cycles IV on days 1, 15, and 29 of the 42 day cycle OR Placebo
干预措施: Botensilimab (Drug)
Cohort 2b: MSS CRLM (Botensilimab and Balstilimab vs. Placebo) Randomized
All patients will receive botensilimab IV on day 1 of the 42 day cycle for 4 doses, balstilimab IV on days 1, 15, and 29 of the 42 day cycle. Patient then continues balstilimab alone for an additional two cycles IV on days 1, 15, and 29 of the 42 day cycle OR Placebo
干预措施: Balstilimab (Drug)
Cohort 2b: MSS CRLM (Botensilimab and Balstilimab vs. Placebo) Randomized
All patients will receive botensilimab IV on day 1 of the 42 day cycle for 4 doses, balstilimab IV on days 1, 15, and 29 of the 42 day cycle. Patient then continues balstilimab alone for an additional two cycles IV on days 1, 15, and 29 of the 42 day cycle OR Placebo
干预措施: Placebo (Other)
Cohort 1a: Stage III MSS Colorectal Cancer (Botensilimab and Balstilimab)
All patients will receive botensilimab IV on day 1 of the 42 day cycle for 4 doses, balstilimab IV on days 1, 15, and 29 of the 42 day cycle. Patient then continues balstilimab alone for an additional two cycles IV on days 1, 15, and 29 of the 42 day cycle.
干预措施: Botensilimab (Drug)
Cohort 1a: Stage III MSS Colorectal Cancer (Botensilimab and Balstilimab)
All patients will receive botensilimab IV on day 1 of the 42 day cycle for 4 doses, balstilimab IV on days 1, 15, and 29 of the 42 day cycle. Patient then continues balstilimab alone for an additional two cycles IV on days 1, 15, and 29 of the 42 day cycle.
干预措施: Balstilimab (Drug)
Cohort 2a: Stage 3 MSS Colorectal Cancer (Botensilimab and Balstilimab vs. Placebo) Randomized
All patients will receive botensilimab IV on day 1 of the 42 day cycle for 4 doses, balstilimab IV on days 1, 15, and 29 of the 42 day cycle. Patient then continues balstilimab alone for an additional two cycles IV on days 1, 15, and 29 of the 42 day cycle OR Placebo
干预措施: Botensilimab (Drug)
Cohort 2a: Stage 3 MSS Colorectal Cancer (Botensilimab and Balstilimab vs. Placebo) Randomized
All patients will receive botensilimab IV on day 1 of the 42 day cycle for 4 doses, balstilimab IV on days 1, 15, and 29 of the 42 day cycle. Patient then continues balstilimab alone for an additional two cycles IV on days 1, 15, and 29 of the 42 day cycle OR Placebo
干预措施: Balstilimab (Drug)
Cohort 2a: Stage 3 MSS Colorectal Cancer (Botensilimab and Balstilimab vs. Placebo) Randomized
All patients will receive botensilimab IV on day 1 of the 42 day cycle for 4 doses, balstilimab IV on days 1, 15, and 29 of the 42 day cycle. Patient then continues balstilimab alone for an additional two cycles IV on days 1, 15, and 29 of the 42 day cycle OR Placebo
干预措施: Placebo (Other)
结局指标
主要结局
Rate of ctDNA clearance (Cohort 1a)
时间窗: 6 months
The 6 months ctDNA clearance will be estimated using the binomial distribution along with exact 95% confidence intervals separately in each cohort.
Rate of ctDNA clearance (Cohort 1b)
时间窗: 6 months
The 6 months ctDNA clearance will be estimated using the binomial distribution along with exact 95% confidence intervals separately in each cohort.
Recurrence-free survival (RFS) (Cohort 2a)
时间窗: 1 year
Recurrence-free survival (RFS) (Cohort 2b)
时间窗: 1 year
次要结局
未报告次要终点