Botensilimab and Balstilimab Optimization in Colorectal Cancer (BBOpCo)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Proportion of subjects with a best overall response of complete response or partial response according to iRECIST
研究概览
简要总结
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.
详细描述
3.1 Study Description
This is a single-arm, interventional, pilot clinical trial. Subjects with newly diagnosed, metastatic or unresectable, microsatellite stable colorectal cancer without liver, bone, or brain metastases will start study treatment with botensilimab and balstilimab alone. They will have restaging scans every 6 weeks. When the subject experiences progression on the study drug(s), they may choose to add mFOLFOX6 and either bevacizumab or panitumumab to the combination. The determinant of whether the subject crosses over will be radiographic progression (iCPD) per iRECIST. Subjects will continue on the new combination until radiographic or clinical progression, intolerable toxicity, or patient withdrawal.
No more than 20 subjects will be enrolled to ensure the trial obtains 15 evaluable subjects. All patients will be enrolled at the Duke Cancer Institute.
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Enrolled subjects are defined as subjects who give informed consent.
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Screen failures are defined as subjects who give informed consent and do not meet eligibility criteria.
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Accrued subjects are defined as subjects who give informed consent and meet eligibility criteria.
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Withdrawal: Subject accrued but later withdrawn from the study, either before or after receiving a study drug.
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Evaluable: All subjects who are accrued and receive any infusion from Cycle 1 study treatment with botensilimab and balstilimab will be evaluable for safety. Subjects who are accrued, receive C1 study treatment, and complete the first cycle of safety assessments will be considered evaluable for the primary endpoints of disease control rate and safety.
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Non-evaluable: Subjects who accrued but did not complete the first cycle of safety assessments due to reasons other than study treatment-attributed toxicity (e.g., disease progression or inter-current illness) are considered non-evaluable for safety and efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Participants of any gender who are at least 18 years of age on the day of signing informed consent.
- •Histologically confirmed metastatic and/or unresectable colorectal cancer without liver metastasis or known or suspected bone or brain metastases.
- •a. Subjects with lung, lymph node, and locoregional sites of disease (primary tumor or serosal implant) are permitted. Patients with peritoneal carcinomatosis may be included unless they have clinically relevant ascites (See exclusion 17).
- •Microsatellite stable disease, as documented in the participant's medical record at the time of consent by the absence of MSI-H or dMMR result in an FDA-approved assay or an IVD offered as an LDT that includes microsatellite stability biomarker.
- •Subject must be willing to provide fresh biopsy of tumor lesion. *Note: Those who do not have a tumor lesion that is safe and amenable to biopsy may still be enrolled.
- •ECOG performance status of 0 or
- •No prior systemic therapy for colon cancer.
- •a. Subjects who received systemic therapy in the neoadjuvant or adjuvant setting completed at least 6 months prior to enrollment are eligible.
- •Measurable disease per RECIST v1.
- •People of child-bearing potential must not be pregnant or breast feeding and meet at least one of the following conditions:
- •Not a person of childbearing potential (POCBP)
- •A POCBP must agree to use a reliable method of contraception (refer to Section 6.7.1) during the treatment period and for at least 180 days after the last dose of study treatment.
- •All participants must practice effective contraceptive methods (refer to section 6.7.1) during the treatment period, unless documentation of infertility exists.
- •Expected to survive >3 months per investigator assessment.
- •The participant (or legally acceptable representative if applicable) provides written informed consent for the trial
- •Adequate organ function as defined below. Specimens must have been collected within 7 days prior to the start of study treatment:
- •Absolute neutrophil count (ANC) ≥1,500/µL
- •Platelets ≥100,000/µL
- •Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L (Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within the last 2 weeks)
- •Measured or calculated creatinine clearance (GFR can be used in place of CrCl) ≥45 mL/min (Creatinine clearance (CrCl) should be calculated per institutional standard)
- •Total bilirubin ≤1.5 x ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels > 1.5 x ULN
- •AST (SGOT) and ALT (SGPT) ≤2.5 x ULN
- •International normalized ratio (INR) OR prothrombin time (PT) ≤1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT is within therapeutic range of intended use of anticoagulants
排除标准
- •Prior therapy with an immune checkpoint inhibitor.
- •A POCBP who is pregnant or breastfeeding or has a positive pregnancy test within 72 hours prior to receiving study treatment
- •Not willing to use an effective method of birth control as defined in section 6.7.1
- •Known liver, bone, or CNS metastases and/or carcinomatous meningitis.
- •Diagnosis of other carcinomas within the last 2 years, except cured non-melanoma skin cancer, treated thyroid cancer, curatively treated in-situ cervical cancer, or localized prostate cancer treated curatively with no evidence of biochemical or imaging recurrence.
- •Documented history of clinically significant autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo, type 1 diabetes mellitus, psoriasis not requiring systemic treatment, well-controlled hypothyroidism, or conditions not expected to recur in the absence of and external trigger are permitted to enroll.
- •Any history of chronic or autoimmune pancreatitis.
- •Known history of or any evidence of active, non-infectious pneumonitis.
- •Current use of medications specified by the protocol as prohibited for administration in combination with study drug.
- •Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to the start of study drug are not eligible.
- •Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- •Corticosteroids administered as pre-medication for IV contrast allergy are also allowed.
- •Received a live vaccine within 30 days prior to the start of study drug.
- •Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed. However, intranasal influenza vaccines (e.g. Flu-Mist) are live-attenuated vaccines, and are not allowed within 28 days of study treatment
- •COVID-19 vaccines will be allowed. However, COVID vaccines are not allowed within 7 days of starting study drug treatment
- •Recent or current active infectious disease requiring systemic antivirals, antibiotics or antifungals, or treatment within 2 weeks prior to the start of study drug.
- •Concurrent severe and/or uncontrolled medical conditions, which may compromise participation in the study, including impaired heart function or clinically significant heart disease.
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the start of study drug (56 days for hepatectomy, open thoracotomy, major neurosurgery) or anticipation of need for major surgical procedure during the course of the study.
- •Serious, non-healing wound, ulcer, or bone fracture.
- •Patients with a history of organ or allogenic hematopoietic stem cell transplantation.
- •Partial or complete bowel obstruction within the last 3 months, signs/ symptoms of bowel obstruction, or known radiologic evidence of impeding obstruction.
- •Refractory ascites defined as requiring 2 or more therapeutic paracenteses within the last 4 weeks or ≥4 times within the last 90 days or ≥1 time within the last 2 weeks prior to study entry or requiring diuretics within 2 weeks of study entry.
- •Tumor location or size that may result in life-threatening complications. For example, lesions that may put patient at risk for intestinal perforation or obstruction.
- •Known or suspected allergy or hypersensitivity to any investigational or standard of care therapy agents, or any of the inactive ingredients in any of the components of the study drug regimen.
- •Peripheral neuropathy from prior neoadjuvant or adjuvant oxaliplatin must have resolved to G2 or lower.
研究组 & 干预措施
Treatment
botensilimab + balstilimab until disease progression, then botensilimab + balstilimab + mFOLFOX6 (leucovorin, fluorouracil, oxaliplatin) + {bevacizumab or panitumumab}
干预措施: Botensilimab (Drug)
Treatment
botensilimab + balstilimab until disease progression, then botensilimab + balstilimab + mFOLFOX6 (leucovorin, fluorouracil, oxaliplatin) + {bevacizumab or panitumumab}
干预措施: Balstilimab (Drug)
Treatment
botensilimab + balstilimab until disease progression, then botensilimab + balstilimab + mFOLFOX6 (leucovorin, fluorouracil, oxaliplatin) + {bevacizumab or panitumumab}
干预措施: Oxaliplatin (Drug)
Treatment
botensilimab + balstilimab until disease progression, then botensilimab + balstilimab + mFOLFOX6 (leucovorin, fluorouracil, oxaliplatin) + {bevacizumab or panitumumab}
干预措施: Leucovorin (Drug)
Treatment
botensilimab + balstilimab until disease progression, then botensilimab + balstilimab + mFOLFOX6 (leucovorin, fluorouracil, oxaliplatin) + {bevacizumab or panitumumab}
干预措施: Fluorouracil (Drug)
Treatment
botensilimab + balstilimab until disease progression, then botensilimab + balstilimab + mFOLFOX6 (leucovorin, fluorouracil, oxaliplatin) + {bevacizumab or panitumumab}
干预措施: Bevacizumab (Drug)
Treatment
botensilimab + balstilimab until disease progression, then botensilimab + balstilimab + mFOLFOX6 (leucovorin, fluorouracil, oxaliplatin) + {bevacizumab or panitumumab}
干预措施: Panitumumab (Drug)
结局指标
主要结局
Proportion of subjects with a best overall response of complete response or partial response according to iRECIST
时间窗: up to 2 years
The number of subjects who went on treatment and had a complete response or partial response sometime during the study (prior to progression) divided by the number of subjects who went on treatment.
Disease control rate based on iRECIST at second restaging scan
时间窗: 24 weeks after screening
Disease control rate is defined as the proportion of subjects who have a complete response, partial response, or stable disease at the time of a second restaging scan. Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable disease is defined as a decrease of less than 30% or an increase of less than 20%. Increases of 20% or greater must be confirmed 4-8 weeks later, and confirmation scans must also show an increase of at least 5 mm in the sum of lesion sizes or an increase in the number of lesions. Otherwise, the increase will be counted as stable disease.
次要结局
- Proportion of subjects with a best overall response of complete response or partial response according to RECIST v1.1(up to 2 years)
- Months of overall survival(up to 2 years)
- Months of progression-free survival(up to 2 years)
- Disease control rate based on RECIST v1.1 at second restaging scan(24 weeks after screening)
研究者
Nicholas DeVito, MD
Assistant Professor of Medicine
Duke University