NCT06027086招募中1 期
A Phase 1b/2 Study of Glutamine Antagonist DRP-104 in Combination With Durvalumab in Patients With Advanced Stage Fibrolamellar Hepatocellular Carcinoma (FLC)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins2 个研究点 分布在 1 个国家目标入组 27 人开始时间: 2024年2月12日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 27
- 试验地点
- 2
- 主要终点
- Number of participants experiencing drug-related adverse events (AEs) requiring treatment discontinuation
研究概览
简要总结
The purpose of this study is to determine whether the combination of subcutaneous DRP-104 in combination with intravenous Durvalumab 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 (Fibrolamellar Carcinoma) 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.
- •Eastern Cooperative Oncology Group (ECOG) 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
- •Must have had chemotherapy or other systemic therapy or radiotherapy, as follows:
- •Patients who have had chemotherapy, biological cancer therapy, or radiation 21 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 21 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 investigational new drug (IND) Sponsor.
- •Patients with corrected QT interval (QTc) prolongation > 470 ms according to Fridericia formula.
- •Patients receiving potent inducers of Cytochrome P450 3A (CYP 3A4/5) (including apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin and St. John's Wort) that cannot be discontinued at least 14 days prior to Cycle 1 Day
- •Known sensitivity to or history of allergic reactions attributed to compounds of similar chemical or biologic composition of DRP-104 or durvalumab.
- •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 hepatitis B virus (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.
- •Patient is 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.
- •Participants a with history of prior unacceptable and/or life-threatening toxicities attributed to anti-programmed death-receptor 1 (PD1) or anti-PD-L1 (anti-programmed death-receptor 1) therapy.
- •Has active autoimmune disease that has required systemic treatment in the past 2 years.
- •Prior allogeneic stem cell transplantation or organ transplantation.
- •Has a diagnosis of immunodeficiency.
- •Systemic corticosteroids at immunosuppressive doses.
- •Patients who have had either of the following procedures or medications within 4 weeks prior to initiation of study treatment:
- •Any live, attenuated vaccine
- •Allergen hypo sensitization therapy in the last 2 weeks
研究组 & 干预措施
Durvalumab and DRP-104
Experimental
干预措施: Durvalumab (Drug)
Durvalumab and DRP-104
Experimental
干预措施: DRP-104 (Drug)
结局指标
主要结局
Number of participants experiencing drug-related adverse events (AEs) requiring treatment discontinuation
时间窗: 4 years
When calculating the incidence of AEs, each AE (as defined by NCI Common Terminology Criteria for Adverse Events \[CTCAE\] v5.0) 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 (glutamine antagonist) in combination with duvalumab, 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.
次要结局
- Progression-free Survival (PFS)(4 years)
- Overall survival (OS)(4 years)
研究者
研究点 (2)
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