NCT07430202尚未招募1 期
A Phase 1b Study of a DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Glutamine Antagonist DRP-104, Nivolumab, and Ipilimumab for Patients With Advanced Stage Fibrolamellar Hepatocellular Carcinoma (FLC)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins1 个研究点 分布在 1 个国家目标入组 27 人开始时间: 2026年9月1日最近更新:
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Number of participants experiencing grade 3 or above drug-related toxicities
研究概览
简要总结
The purpose of this study is to determine whether the combination of a neoantigen vaccine targeting the DNAJB1-PRKACA fusion kinase in combination with DRP-104, Nivolumab and Ipilimumab is safe and yields a clinically compelling antitumor activity measured as based on objective response rate (ORR, assessed by RECIST 1.1). Secondary objectives include progression-free survival (PFS) and overall survival (OS).
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have histologically confirmed FLC that is metastatic or unresectable.
- •Presence of DNAJB1-PRKACA fusion transcript, assessed by RNA-sequencing, DNA-sequencing, or in situ hybridization in the archival tissue.
- •Must have demonstrated radiographic progression on prior or current immunotherapy.
- •Age ≥ 12 years.
- •Patients < 18 years old must have a body weight ≥ 40 kg.
- •ECOG (Eastern Cooperative Oncology Group) performance status of ≤2
- •Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
- •Patients must have adequate kidney and liver function defined by study-specified laboratory tests.
- •Must have measurable disease per RECIST 1.1
- •Willingness to provide tissue and blood samples for mandatory translational research.
- •Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test.
- •For both Women and 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
- •Patients with a history of prior treatment with checkpoint inhibitors, such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, anti-CTLA-4, or anti-LAG-3 antibodies.
- •Must have had chemotherapy or other systemic therapy or radiotherapy, as follows:
- •Patients who have had chemotherapy, biological cancer therapy, or radiation 14 days prior to the first dose of study drug.
- •Patients who have had surgery within 28 days of dosing of investigational agent, excluding minor procedures.
- •Patients who have received other approved or investigational agents or device within 28 days of the first dose of study drug.
- •Patients who have not recovered from acute adverse events to grade ≤1 or baseline due to agents administered, with exception of grade 2 fatigue, rash, and endocrinopathy successfully managed hormone replacement therapy, or alopecia or stable neuropathy, unless approved by the IND Sponsor.
- •Patients who have received any non-oncology live vaccine therapy used for prevention of infectious diseases within 28 days of study treatment.
- •Known sensitivity to or history of allergic reactions attributed to compounds of similar chemical or biologic composition of polyinosinic-polycytidylic acid (Poly-ICLC) and/or DRP-104 and/or nivolumab and/or ipilimumab.
- •History of severe hypersensitivity reaction to any monoclonal antibody.
- •Has an active autoimmune disease.
- •Prior allogeneic stem cell transplantation or organ transplantation.
- •Has a diagnosis of immunodeficiency.
- •Systemic corticosteroids at immunosuppressive doses.
- •Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
- •Has a pulse oximetry of <92% on room air or is on supplemental home oxygen.
- •Active or untreated brain metastases or leptomeningeal metastases.
- •Uncontrolled intercurrent active medical and/or psychiatric illness/social psychosocial problems that that would limit compliance with study requirements.
- •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.
- •Pregnant or breastfeeding.
- •Has a known history of Human Immunodeficiency Virus (HIV)/AIDS.
- •Has active hepatitis B. Patients with chronic or acute HBV infection.
- •Have had evidence of active or acute diverticulitis, intra-abdominal abscess, or GI obstruction which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study.
- •Unwilling or unable to follow the study schedule for any reason.
- •Patient is at the time of signing informed consent a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).
- •Evidence of clinical ascites.
- •Patients with QTc prolongation > 470 ms according to Fridericia formula.
- •Patients receiving potent inducers of CYP 3A4/5 (including but not limited to apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin and St. John's Wort) who cannot safely discontinue drug at least 14 days prior to Cycle 1 Day
- •Have had an allergen hyposensitization therapy within 2 weeks prior to initiation of study treatment.
研究组 & 干预措施
Arm A - DNAJB1-PRKACA Peptide Vaccine with poly-ICLC adjuvant, DRP-104, Nivolumab and Ipilimumab
Experimental
干预措施: DNAJB1-PRKACA Peptide Vaccine (Drug)
Arm A - DNAJB1-PRKACA Peptide Vaccine with poly-ICLC adjuvant, DRP-104, Nivolumab and Ipilimumab
Experimental
干预措施: DRP-104 (Drug)
Arm A - DNAJB1-PRKACA Peptide Vaccine with poly-ICLC adjuvant, DRP-104, Nivolumab and Ipilimumab
Experimental
干预措施: Nivolumab (Drug)
Arm A - DNAJB1-PRKACA Peptide Vaccine with poly-ICLC adjuvant, DRP-104, Nivolumab and Ipilimumab
Experimental
干预措施: Ipilimumab (Drug)
结局指标
主要结局
Number of participants experiencing grade 3 or above drug-related toxicities
时间窗: 4 years
When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v6.0) will be counted only once for a given subject.
Objective response rate (ORR) using immune Response Evaluation Criteria for Solid Tumors (RECIST 1.1)
时间窗: 4 years
ORR is defined as the percentage of patients achieving a complete response (CR) or partial response (PR) to DRP-104 in combination with DRP-104, Nivolumab and Ipilimumab, based on the immune 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.
次要结局
- Progression-free Survival (PFS) number of months according to RECIST (1.1) criteria.(4 years)
- Overall survival (OS) of patients treated with study drug combination(4 years)
研究者
研究点 (1)
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