A Phase 1/2, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Antitumor Activity of TNG456 Monotherapy and in Combination With Abemaciclib in Patients With Solid Tumors With MTAP Loss
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 191
- 试验地点
- 17
- 主要终点
- Phase 1 Maximum Tolerated Dose
研究概览
简要总结
This is a first in human study of TNG456 alone and in combination with abemaciclib in patients with advanced or metastatic solid tumors known to have an MTAP loss. The first part of the study is an open-label, dose escalation and the second part is an open label dose expansion in specific solid tumor types with a confirmed MTAP loss. The study drug, TNG456, is a selective PRMT5 inhibitor administered orally. The study is planned to treat up to 191 participants.
详细描述
This is a Phase 1/2 multi-center, open label study in solid tumor patients who have a confirmed MTAP loss in their tumor. The Phase 1 portion is a dose escalation study of oral TNG456 administered as a single agent and in combination with oral abemaciclib in solid tumor patients with confirmed MTAP loss. In the Phase 2 expansion part of the study, 6 arms defined by confirmed tumor types will enroll in parallel at the RP2D(s) of TNG456 and in combination. In both parts of the study participants who tolerate the drug may continue treatment until disease progression.
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
- •Has a tumor with a confirmed MTAP loss
- •Is ≥18 years of age at the time of signature of the main study ICF
- •Has had progression or an inadequate response to or is intolerant of the approved standard of care therapy, no standard of care therapy exists, or the investigator has determined that treatment with the standard of care therapy is not appropriate.
- •Is able to swallow tablets
- •Adequate Organ function/reserve per local labs
- •Negative serum pregnancy test result at screening
- •Has an ECOG performance status score of 0 to 1
- •Has measurable disease based on RECIST v1.1 or a confirmed glioblastoma (IDH-wildtype) with radiographic evidence of disease progression or recurrence defined by RANO 2.
- •Has an ECOG performance score of 0 to 1 or for GBM has a Karnofsky performance status score ≥70.
排除标准
- •A female patient is who is pregnant or breastfeeding
- •Has impaired GI function or disease that may significantly alter the absorption of oral study treatment(s)
- •Has an active infection requiring systemic therapy
- •Has received prior treatment with a PRMT5 inhibitor or a MAT2A inhibitor
- •Patients in the expansion receiving the combination therapy that have received prior treatment with a CDK4/6 inhibitor
- •Clinically relevant cardiovascular disease
- •Has a prior or ongoing clinically significant illness may affect the safety of the patient, impair the assessment of study results or compliance with the protocol
研究组 & 干预措施
Single Agent and Combination Dose Escalation
Solid tumor participants with confirmed MTAP loss will receive escalating doses of TNG456 single agent and in combination with abemaciclib to estimate the MTD
干预措施: TNG456 (Drug)
Tumor Agnostic Combination Expansion
Participants with specific tumor types with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib
干预措施: abemaciclib (Drug)
NSCLC Single Agent Dose Expansion
NSCLC (squamous and non squamous) participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s)
干预措施: TNG456 (Drug)
Tumor Agnostic Single Agent Dose Expansion
Patients with specific solid tumor types that have a confirmed MTAP loss will receive TNG456 at the identified RP2D(s)
干预措施: TNG456 (Drug)
Single Agent and Combination Dose Escalation
Solid tumor participants with confirmed MTAP loss will receive escalating doses of TNG456 single agent and in combination with abemaciclib to estimate the MTD
干预措施: abemaciclib (Drug)
Tumor Agnostic Combination Expansion
Participants with specific tumor types with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib
干预措施: TNG456 (Drug)
GBM Combination Expansion
GBM participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib
干预措施: abemaciclib (Drug)
GBM Single Agent Dose Expansion
GBM participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s)
干预措施: TNG456 (Drug)
GBM Combination Expansion
GBM participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib
干预措施: TNG456 (Drug)
NSCLC Combination Expansion
NSCLC (squamous and non-squamous) participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib
干预措施: abemaciclib (Drug)
NSCLC Combination Expansion
NSCLC (squamous and non-squamous) participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib
干预措施: TNG456 (Drug)
结局指标
主要结局
Phase 1 Maximum Tolerated Dose
时间窗: 21 days
To determine the MTD, recommended dose(s) (RD), and dosing schedule of TNG456 monotherapy and in combination with abemaciclib
Phase 2 Anti-neoplastic Activity Single Agent
时间窗: 18 weeks
To assess the antitumor activity of TNG456 in patients with advanced or metastatic solid tumors with MTAP loss by RECIST or modified RANO criteria
Phase 2 Anti-neoplastic Activity Combination Treatment
时间窗: 18 weeks
To assess the antitumor activity of TNG456 in combination with abemaciclib in patients with advanced or metastatic tumors with MTAP loss by RECIST or modified RANO criteria
次要结局
- Phase 1 Anti-neoplastic Activity Single Agent(18 weeks)
- Phase 1 and 2 Adverse Event Profile(21 days)
- Phase 1 and 2 Concentration versus Time Curve(16 days)
- Phase 1 and 2 Time to Achieve Maximal Plasma Concentration(16 days)
- Phase 1 and 2 Maximum Observed Plasma Concentration(16 days)