A Phase 1/2, Multicenter, Open-Label Study to Evaluate Safety, Tolerability & Antitumor Activity of TNG462 in Combination With Other Agents in Patients With Pancreatic Cancer With MTAP Loss and Pancreatic or Non-Small Cell Lung Cancer With MTAP Loss & RAS Mutation
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 183
- 试验地点
- 30
- 主要终点
- Phase 1: Maximum Tolerated Dose
研究概览
简要总结
TNG462-C102 is a Phase 1/2, open-label, multicenter study designed to determine the safety, tolerability, PK, PD, and preliminary antineoplastic activity of oral TNG462 in combination with RMC-6236, RMC-9805, mFOLFIRINOX or gemcitabine/nab-paclitaxel. The study comprises a dose escalation phase and a dose expansion phase.
详细描述
TNG462-C102 is a Phase 1/2, open-label, multicenter study designed to determine the safety, tolerability, PK, PD, and preliminary antineoplastic activity of oral TNG462 in combination with RMC-6236, RMC-9805, mFOLFIRINOX or gemcitabine/nab-paclitaxel.
For the RAS inhibitor arms, the study will be conducted in patients with MTAP loss and RAS mutant metastatic pancreatic adenocarcinoma (PDAC) or locally advanced or metastatic non-small cell lung cancer (NSCLC). For the chemotherapy specific arms, the study will be conducted in patients with MTAP loss locally advanced or metastatic PDAC. The entire study (all arms) will be conducted in 2 parts: Phase 1 (dose escalation) and Phase 2 (dose expansion).
Individual Arms in the dose expansion phase may open once the MTD and/or RD(s) has been determined for the corresponding combination in the dose escalation phase of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Is ≥18 years of age at the time of signature of the main study ICF.
- •Has an ECOG PS of 0 or
- •Has a tumor with loss of MTAP protein or bi-allelic deletion of the MTAP gene
- •Arms A and B only: Has a tumor with a RAS mutation
- •Pathologically documented metastatic PDAC or locally advanced, recurrent or metastatic NSCLC
- •Has received prior standard therapy
- •Arms A and B only: Must not have received prior RAS-targeted therapy
- •Has evidence of measurable disease based on RECIST v1.
- •Adequate organ function
- •Must be able to swallow tablets.
- •Negative pregnancy test at screening
- •Written informed consent must be obtained according to local guidelines
排除标准
- •Has received prior treatment with a PRMT5 inhibitor, or MAT2A inhibitor
- •Arms A and B only: Prior enrollment in any phase 3 clinical trial of RMC-6236 or RMC-9805
- •Known allergy, hypersensitivity or intolerance to TNG462 (all arms), RMC-6236 Arm A), RMC-9805 (Arm B), mFOLFIRINOX (Arm C), gemcitabine/nab-paclitaxel (Arm D) or their excipients
- •Has uncontrolled intercurrent illness that will limit compliance with the study requirements.
- •Has an active infection requiring systemic therapy.
- •Is currently participating in or has planned concurrent participation in a study of another investigational agent or device.
- •Has impairment of GI function or disease that may significantly alter the absorption of the oral medications
- •Has known or suspected active or untreated CNS metastases associated with progressive neurological symptoms
- •Has current active liver disease from any cause
- •Is known to be HIV positive, unless all the following criteria are met:
- •CD4+ count ≥300/µL.
- •Undetectable viral load.
- •Receiving highly active antiretroviral therapy
- •Has clinically relevant cardiovascular disease
- •History of or presence of active interstitial lung disease
- •Is a female patient who is pregnant or lactating
- •Is unwilling or unable to comply with the scheduled visits, study treatment administration plan, laboratory tests or other study procedures and study restrictions.
- •Has a prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator's opinion may affect the safety of the patient or impair the ability to assess study results
研究组 & 干预措施
Experimental: Dose Escalation 1C
Escalating doses of TNG462 in combination with mFOLFIRINOX
干预措施: mFOLFIRINOX (Drug)
Dose Expansion 2A
Expansion arm at the RDE(s) of oral TNG462 in combination with oral RMC-6236
干预措施: RMC-6236 (Drug)
Dose Expansion 2B
Expansion arm at the RDE(s) of oral TNG462 in combination with oralRMC-9805
干预措施: TNG462 (Drug)
Experimental: Dose Escalation 1D
Escalating doses of TNG462 in combination with gemcitabine/nab-paclitaxel
干预措施: gemcitabine/nab-paclitaxel (Drug)
Dose Escalation 1A
Escalating oral doses of TNG462 in combination with oral RMC-6236
干预措施: RMC-6236 (Drug)
Dose escalation 1B
Escalating oral doses of TNG462 in combination with oral RMC-9805
干预措施: TNG462 (Drug)
Experimental: Dose Escalation 1D
Escalating doses of TNG462 in combination with gemcitabine/nab-paclitaxel
干预措施: TNG462 (Drug)
Experimental: Dose Expansion 2C
Expansion arm at the RDE(s) of TNG462 in combination with mFOLFIRINOX
干预措施: mFOLFIRINOX (Drug)
Experimental: Dose Expansion 2D
Expansion arm at the RDE(s) of TNG462 in combination with gemcitabine/nab-paclitaxel
干预措施: TNG462 (Drug)
Dose Expansion 2A
Expansion arm at the RDE(s) of oral TNG462 in combination with oral RMC-6236
干预措施: TNG462 (Drug)
Experimental: Dose Expansion 2D
Expansion arm at the RDE(s) of TNG462 in combination with gemcitabine/nab-paclitaxel
干预措施: gemcitabine/nab-paclitaxel (Drug)
Dose Expansion 2B
Expansion arm at the RDE(s) of oral TNG462 in combination with oralRMC-9805
干预措施: RMC-9805 (Drug)
Experimental: Dose Escalation 1C
Escalating doses of TNG462 in combination with mFOLFIRINOX
干预措施: TNG462 (Drug)
Dose Escalation 1A
Escalating oral doses of TNG462 in combination with oral RMC-6236
干预措施: TNG462 (Drug)
Dose escalation 1B
Escalating oral doses of TNG462 in combination with oral RMC-9805
干预措施: RMC-9805 (Drug)
Experimental: Dose Expansion 2C
Expansion arm at the RDE(s) of TNG462 in combination with mFOLFIRINOX
干预措施: TNG462 (Drug)
结局指标
主要结局
Phase 1: Maximum Tolerated Dose
时间窗: 21 days
To determine the MTD and RD(s) of TNG462 in combination with RMC-6236 or RMC-9805
Phase 1: Maximum Tolerated Dose
时间窗: 28 days
To determine the MTD and RD(s) of TNG462 in combination with mFOLFIRINOX or gemcitabine/nab-paclitaxel
Phase 2: Combination Anti-neoplastic Activity
时间窗: 12 weeks
To assess preliminary evidence of antineoplastic activity of TNG462 in combination with RMC-6236, RMC-9805, mFOLFIRINOX or gemcitabine/nab-paclitaxel using RECIST 1.1
次要结局
- Phase 1 and 2: Cmax of TNG462 and in Combination(21 days)
- Phase 1 and 2: Tmax of TNG462 and in Combination(21 days)
- Phase 1 and 2: AUC of TNG462 and in Combination(21 days)
- Phase 1 and 2 Adverse Event Profile(21 days)
- Phase 1: Combination Anti-neoplastic Activity(12 weeks)
- Phase 1 and 2: Tmax of TNG462 and in Combination(28 days)
- Phase 1 and 2 Adverse Event Profile(28 days)
- Phase 1 and 2: Cmax of TNG462 and in Combination(28 days)
- Phase 1 and 2: AUC of TNG462 and in Combination(28 days)