Pooled Mutant KRAS-Targeted Long Peptide Vaccine Combined With Balstilimab and Botensilimab for Patients With Stage IV MMR-p Colorectal Cancer and Pancreatic Ductal Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 54
- 试验地点
- 2
- 主要终点
- Cohort A: Progression-free Survival (PFS) for maintenance mPDAC cohort
研究概览
简要总结
Phase 1b study evaluating the efficacy and immune response to a synthetic long peptide mutant KRAS vaccine (SPL mKRASvax) combined with Balstilimab and Botensilimab for unresectable or metastatic mismatch repair-proficient (MMR-p) colorectal cancer (mCRC) or unresectable or metastatic MMR-p pancreatic ductal adenocarcinoma (PDAC) patients with measurable disease following first-line chemotherapy.
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
- •Age ≥18 years.
- •Have histologically or cytologically - proven cancer of the pancreas or colon.
- •Have tumor lesions amenable to repeated biopsy, and patient's acceptance to have a tumor biopsy of an accessible lesion at baseline and on treatment if the lesion can be biopsied with acceptable clinical risk (as judged by the investigator).
- •Measurable disease as per RECIST 1.
- •Have sufficient and accessible tissue for next generation sequencing (NGS) and immune-phenotyping.
- •Have one of the KRAS mutations included in the vaccine at the time of vaccination expressed in tumor.
- •Cohort A: Have received 4-6 months of FOLFIRINOX or gemcitabine+nab-paclitaxel for the 1st line treatment of metastatic unresectable PDAC.
- •Cohort B: Have received 4-6 months of 1st line SOC chemotherapy per NCCN guidelines (FOLFIRINOX, FOLFOX, FOLFIRI +/- targeted therapy with VEGFi or EGFRi) of metastatic CRC.
- •Cohort C: Have received no more than 3 lines of systemic chemotherapy, including prior KRAS inhibitor.
- •Eastern Cooperative Oncology Group (ECOG) performance status
- •Life expectancy of greater than 3 months.
- •Patients must have adequate organ and marrow function defined by study-specified laboratory tests prior to initial study drug.
- •Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol.
- •Men must use acceptable form of birth control while on study.
- •Ability to understand and willingness to sign a written informed consent document.
排除标准
- •Is a candidate for definitive surgical resection.
- •Known history or evidence of brain metastases and/or leptomeningeal spread.
- •Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, etc.).
- •Receiving active immunosuppressive agents or chronic use of systemic corticosteroids within 14 days of vaccine treatment.
- •Has active autoimmune disease that has required systemic treatment in the past 5 years, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
- •Known history or concurrent interstitial lung disease.
- •Has a pulse oximetry < 95% on room air.
- •Requires the use of home oxygen.
- •Infection with HIV or hepatitis B or C.
- •Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Has been diagnosed with another cancer or myeloproliferative disorder in the past 5 years except for superficial bladder cancer, non-melanoma skin cancers, DCIS, a low-grade prostate cancer, or a cancer not expected to impact life expectancy and not requiring therapy.
- •Has had surgery within 28 days of dosing of investigational agent, excluding minor procedures (dental work, skin biopsy, etc.), celiac plexus block, and biliary stent placement.
- •Has received any non-oncology live vaccine therapy used for prevention of infectious diseases within 28 days of study treatment.
- •If at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or other substance abuse (including alcohol) that could potentially interfere with adherence to study procedures or requirements.
- •Any other sound medical, psychiatric, and/or social reason as determined by the Investigator.
- •Unwilling or unable to follow the study schedule for any reason.
- •Are pregnant or breastfeeding.
- •Any radiological or clinical pleural effusions or ascites.
- •History of malignant small bowel obstruction.
- •On parenteral nutrition.
- •Known or suspected hypersensitivity to Hiltonol.
研究组 & 干预措施
SLP mKRASvax (Up to 1.8mg peptide + 0.5 mg Poly-ICLC (Hiltonol), Botensilimab and Balstilimab
干预措施: KRAS Vaccine with Poly-ICLC adjuvant (Drug)
SLP mKRASvax (Up to 1.8mg peptide + 0.5 mg Poly-ICLC (Hiltonol), Botensilimab and Balstilimab
干预措施: Balstilimab (Drug)
SLP mKRASvax (Up to 1.8mg peptide + 0.5 mg Poly-ICLC (Hiltonol), Botensilimab and Balstilimab
干预措施: Botensilimab (Drug)
结局指标
主要结局
Cohort A: Progression-free Survival (PFS) for maintenance mPDAC cohort
时间窗: 4 months
PFS is defined as the number of mPDAC patients free of progression at 4 months since the initiation of therapy - disease progression (progressive disease \[PD\] or relapse from complete response \[CR\] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30percent decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20percent increase in sum of diameters of target lesions, Stable Disease (SD) is \<30percent decrease or \<20percent increase in sum of diameters of target lesions.
Cohort B: Objective Response Rate (ORR) for maintenance mCRC cohort
时间窗: 3 years
ORR is defined as the number of mCRC patients who are administered at least 1 dose of SLP mKRASvax achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =\>30percent decrease in sum of diameters of target lesions, progressive disease (PD) is \>20percent increase in sum of diameters of target lesions, stable disease (SD) is \<30percent decrease or \<20percent increase in sum of diameters of target lesions.
Cohort C: Objective Response Rate (ORR) for KRAS-inhibitor exposed mPDAC cohort
时间窗: 3 years
ORR is defined as the number of mCRC patients who are administered at least 1 dose of SLP mKRASvax achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =\>30percent decrease in sum of diameters of target lesions, progressive disease (PD) is \>20percent increase in sum of diameters of target lesions, stable disease (SD) is \<30percent decrease or \<20percent increase in sum of diameters of target lesions.
Number of participants experiencing study drug-related toxicities
时间窗: 3 years
Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0
次要结局
- Disease Control Rate (DCR)(2 months)
- Disease Control Rate (DCR)(6 months)
- Progression-free Survival (PFS) per RECIST 1.1(3 years)
- Objective Response Rate (ORR) per RECIST 1.1(3 years)
- Disease Control Rate (DCR)(12 months)