A Pilot Study of Botensilimab and Balstilimab and SBRT in Non-MSI-H or pMMR Colorectal Cancer With Liver Metastasis
概览
- 阶段
- 早期 1 期
- 状态
- 尚未招募
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Incidence of dose limiting radiation-related toxicities
概览
简要总结
This is a single-arm pilot feasibility study evaluating the combination of Botensilimab and Balstilimab with Radiation Therapy (RT) in Non-Microsatellite Instability High (MSI-H) or Proficient Mismatch Repair (pMMR) chemorefractory colorectal cancer (CRC) with liver metastasis.
详细描述
In this open-label study, the investigators propose to use standard of care (SOC) radiation (Stereotactic Body Radiation Therapy (SBRT)) to control the liver lesions in combination with investigational dual checkpoint inhibitors, botensilimab (AGEN1181) and balstilimab (AGEN2034).
Initially, 5 patients will be enrolled in a lead-in cohort and assessed for dose-limiting toxicity (DLT) related to radiation during Cycle 1. If DLT are observed in 2 or more of the first 5 patients, the protocol will be stopped early. If DLT were observed in 0 or 1 of the first 5 patients during the lead-in, enrollment will be expanded to a total of 15 patients. After screening, participants will receive SOC SBRT for 2-3 weeks, and botensilimab + balstilimab for up to 24 weeks followed by balstilimab alone for 14 additional 6-week cycles, for a total treatment time of up to 108 weeks. Participants will be followed for 1 year.
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 must have histologically or cytologically confirmed adenocarcinoma of colorectal origin.
- •MSS or pMMR status confirmed by IHC or PCR.
- •Must have at least 1 measurable (≥ 1 cm) previously unirradiated hepatic lesion amenable to ablative RT and meeting dose constraints. A maximum of 5 hepatic lesions are allowed provided all are amenable to ablative RT and meet dose constraints. Must have at least 1 other unirradiated measurable (≥ 1cm) extrahepatic lesion, outside of RT field. Patients should ideally have a second unirradiated lesion, outside of RT field, that would be amenable for paired biopsies.
- •Must have received or confirmed intolerance to 5-FU, Oxaliplatin, and Irinotecan (in any combination).
- •Age ≥18 years
- •ECOG performance status ≤ 1
- •Life expectancy of greater than 3 months.
- •Participants must meet the following organ and marrow function as defined below:
- •Absolute Neutrophil Count (ANC) ≥ 1500 /mcL
- •White Blood Cells (WBC) ≥ 2000 /mcL
排除标准
- •Participants who have had chemotherapy, targeted small molecule therapy or study therapy within 14 days prior to starting protocol treatment, or those who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 2 weeks earlier.
- •EXCEPTION: Participants with ≤ Grade 2 neuropathy are permitted.
- •If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting protocol treatment.
- •Known or suspected, active, autoimmune disease
- •Condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to study drug administration.
- •-EXCEPTIONS: Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \>10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
- •Positive TB (Bacillus Tuberculosis) at screening. NOTE: skin test is not allowed. Interferon-Gamma Release Assay (IGRA)-based tests such as QuantiFERON TB Gold and T-Spot TB tests are acceptable.
- •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 ≥ times within the last 90 days, or ≥ time within the last 2 weeks prior to study entry, or requiring diuretics within 2 weeks of study entry.
- •Known history of active or chronic HBV or HCV infection
研究组 & 干预措施
Stereotactic Body Radiation Therapy (SBRT) + Botensilimab + Balstilimab
Participants will receive:
- standard of care (SOC) SBRT for 2-3 weeks (Cycle 1);
- botensilimab, on Day 1 of 6-week cycles (Cycles 1-4);
- balstilimab, once every 2 weeks (Cycles 1-18, 6-week cycles).
干预措施: Stereotactic Body Radiation Therapy (SBRT) (Radiation)
Stereotactic Body Radiation Therapy (SBRT) + Botensilimab + Balstilimab
Participants will receive:
- standard of care (SOC) SBRT for 2-3 weeks (Cycle 1);
- botensilimab, on Day 1 of 6-week cycles (Cycles 1-4);
- balstilimab, once every 2 weeks (Cycles 1-18, 6-week cycles).
干预措施: Balstilimab (Drug)
Stereotactic Body Radiation Therapy (SBRT) + Botensilimab + Balstilimab
Participants will receive:
- standard of care (SOC) SBRT for 2-3 weeks (Cycle 1);
- botensilimab, on Day 1 of 6-week cycles (Cycles 1-4);
- balstilimab, once every 2 weeks (Cycles 1-18, 6-week cycles).
干预措施: Botensilimab (Drug)
结局指标
主要结局
Incidence of dose limiting radiation-related toxicities
时间窗: Day 1 of treatment through 30 days after completion of radiation therapy (radiation therapy is 2-3 weeks), up to 60 days.
Dose limiting radiation-related toxicities will be assessed by CTCAE v6.0. A dose limiting toxicity (DLT) will be defined as any patient who can't complete all radiation therapy (RT) fractions within 2-3 weeks for pre-specified toxicity or lab values attributable to radiation therapy, or development of RT-related toxicities within 30 days of completion of RT. Participants will be evaluable for DLT once they start protocol therapy.
次要结局
- Response rate of in-field radiated hepatic lesion(s)(Screening through end of Cycle 18 (each cycle is 6 weeks), up to 108 weeks.)
- Response rate of extrahepatic lesion(s)(Screening through end of Cycle 18 (each cycle is 6 weeks), up to 108 weeks.)
- Overall Survival (OS)(Registration through 160 weeks (108 weeks of treatment + 1 year follow-up))
- Progression-Free Survival (PFS)(Registration through up to 108 weeks of treatment)
- Disease Control Rate (DCR)(Day 1 through up to 108 weeks.)
研究者
Aparna Parikh
Principal Investigator
Massachusetts General Hospital