A Phase 1/2, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Anti-tumor Activity of TNG908 in Patients With MTAP-deleted Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 110
- 试验地点
- 31
- 主要终点
- Phase 1:
研究概览
简要总结
This is a first in human study in patients with advanced or metastatic solid tumors known to have an MTAP deletion. The first part of the study is an open-label, dose escalation and the second part is an open label dose expansion in specific MTAP-deleted tumor types. The study drug, TNG908, is a selective PRMT5 inhibitor administered orally. The study is planned to treat up to 192 participants.
详细描述
This is a Phase 1/2 multi-center, open label study in solid tumor patients (including glioblastoma) who have a confirmed homozygous MTAP deletion in their tumor. The Phase 1 portion is a dose escalation study of oral TNG908 in patients with confirmed MTAP-deleted solid tumors. In Phase 2, 6 expansion arms defined by confirmed MTAP-deleted tumor types will enroll in parallel at the RP2D of TNG908. 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 65+ years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: ≥18 years-of-age at the time of signature of the main study ICF
- •Performance status: ECOG Performance Score of 0 to 1 or Karnofsky performance status score ≥
- •Confirmed histologic or cytologic diagnosis of a locally advanced, metastatic, and/or unresectable solid tumor or for GBM, have R/R disease.
- •Prior standard therapy, as available
- •Documented bi-allelic (homozygous) deletion of MTAP in a tumor detected by next- generation sequencing or absence of MTAP protein in a tumor detected by IHC.
- •Adequate organ function/reserve per local labs
- •Adequate liver function per local labs
- •Adequate renal function per local labs
- •Negative serum pregnancy test result at screening
- •Written informed consent must be obtained according to local guidelines
排除标准
- •Known allergies, hypersensitivity, or intolerance to TNG908 or its excipients
- •Uncontrolled intercurrent illness that will limit compliance with the study requirements
- •Active infection requiring systemic therapy
- •Currently participating in or has planned participation in a study of another investigational agent or device
- •Impairment of GI function or disease that may significantly alter the absorption of oral TNG908
- •Active prior or concurrent malignancy.
- •Central nervous system metastases associated with progressive neurological symptoms
- •Current active liver disease from any cause
- •Known to be HIV positive, unless all of the following criteria are met:
- •CD4+ count ≥300/μL
- •Undetectable viral load
- •Receiving highly active antiretroviral therapy
- •Clinically relevant cardiovascular disease
- •A female patient who is pregnant or lactating
- •Patient is unwilling or unable to comply with the scheduled visits, drug administration plan, laboratory tests, biopsy, or other study procedures and study restrictions
- •Patient 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 assessment of study results
研究组 & 干预措施
Dose Expansion in solid tumors
Participants with other MTAP-deleted solid tumors will receive TNG908 at the identified RP2D
干预措施: TNG908 (Drug)
Dose Expansion in Glioblastoma
Participants with MTAP-deleted relapsed/refractory glioblastoma will receive TNG908 at the identified RP2D
干预措施: TNG908 (Drug)
Dose Escalation
Participants with MTAP-deleted solid tumors will receive escalating doses of TNG908 to estimate the MTD
干预措施: TNG908 (Drug)
Dose Expansion in Pancreatic Ductal Adenocarcinoma
Participants with MTAP-deleted pancreatic ductal adenocarcinoma will receive TNG908 at the identified RP2D
干预措施: TNG908 (Drug)
Dose Expansion in Mesothelioma
Participants with MTAP-deleted mesothelioma will receive TNG908 at the identified RP2D
干预措施: TNG908 (Drug)
Dose Expansion in NSCLC
Participants with MTAP-deleted NSCLC (squamous and non squamous) will receive TNG908 at the identified RP2D
干预措施: TNG908 (Drug)
Dose Expansion in Sarcoma
Participants with MTAP-deleted sarcoma (soft tissue and bone) will receive TNG908 at the identified RP2D
干预措施: TNG908 (Drug)
结局指标
主要结局
Phase 1:
时间窗: 28 days
To determine the MTD and dosing schedule of TNG908
Phase 2:
时间窗: 16 weeks
To assess anti-neoplastic activity of TNG908 in patients with MTAP-deleted advanced solid tumors by RECIST or mRECIST v1.1 or modified RANO criteria
Phase 1: Incidence of DLTs within the first 28 days of treatment with TNG908 monotherapy Phase 2: - ORR (CR + PR) as determined by RECIST v1.1, mRECIST v1.1, or modified RANO criteria per investigator assessment - DOR as determined by RECIST v1.1, mRECIST v1.1, or modified RANO criteria per investigator assessment
Phase 1: Incidence of DLTs within the first 28 days of treatment with TNG908 monotherapy Phase 2: - ORR (CR + PR) as determined by RECIST v1.1, mRECIST v1.1, or modified RANO criteria per investigator assessment - DOR as determined by RECIST v1.1, mRECIST v1.1, or modified RANO criteria per investigator assessment
- PFS by investigator assessment - CBR (CR + PR + stable disease) at 16 weeks
- PFS by investigator assessment - CBR (CR + PR + stable disease) at 16 weeks
次要结局
- Phase 1:(16 weeks)
- Phase 1 and 2:(28 days)
- Phase 1 and 2:(16 days)
- "Secondary – Phases 1 and 2 - Type, frequency, severity, timing, and relationship to study treatment of any AEs, SAEs, and changes in vital signs, ECGs, ECOG performance status or Karnofsky performance status, and safety laboratory tests - PK parameters of TNG908 including, but not limited to, Cmax, Tmax, AUC0-t, AUC0-∞, t1/2, λz, CL/F, Vz/F, Rac for Cmax and AUC, and Ctrough - Changes in SDMA levels in tumor after dosing with TNG908 "
研究者
Heather DiBenedetto
Scientific
Tango Therapeutics Inc.