A Phase 1/2, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Anti-tumor Activity of TNG462 as a Single Agent and in Combination in Patients with MTAP-deleted Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 11
- 主要终点
- Phase 1: • Incidence of DLTs within the first 28 days of treatment with TNG462 as a single agent • Incidence of DLTs within the first 21 days of treatment with TNG462 plus pembrolizumab Phase 2: • ORR (CR + PR) as determined by RECIST v1.1, mRECIST v1.1, or iRECIST per investigator assessment • DOR as determined by RECIST v1.1, mRECIST v1.1 or iRECIST per investigator assessment • PFS by investigator assessment • CBR (CR + PR + stable disease) at 16 weeks
研究概览
简要总结
Phase 1: To determine the MTD and RP2D(s) of TNG462 when administered as single agent and in combination with pembrolizumab Phase 2: To assess antineoplastic activity of TNG462 in participants with MTAP-deleted advanced solid tumors when administered as a single agent and in combination with pembrolizumab
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Tng462 Combination With Pembrolizumab Both Phases
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Age: ≥18 years-of-age at the time of signature of the main study ICF
- •Written informed consent must be obtained according to local guidelines
- •Performance status: ECOG Performance Score of 0 to 1
- •Confirmed histologic or cytologic diagnosis of a locally advanced, metastatic, and/or unresectable solid tumor
- •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
排除标准
- •Known allergies, hypersensitivity, or intolerance to TNG462 or its excipients
- •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
- •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 TNG462
- •Active prior or concurrent malignancy.
- •Tener metástasis del SNC asociadas con síntomas neurológicos progresivos
- •Current active liver disease from any cause
- •Known to be HIV positive, unless all of the following criteria are met: a. CD4+ count ≥300/μL b. Undetectable viral load c. Receiving highly active antiretroviral therapy
结局指标
主要结局
Phase 1: • Incidence of DLTs within the first 28 days of treatment with TNG462 as a single agent • Incidence of DLTs within the first 21 days of treatment with TNG462 plus pembrolizumab Phase 2: • ORR (CR + PR) as determined by RECIST v1.1, mRECIST v1.1, or iRECIST per investigator assessment • DOR as determined by RECIST v1.1, mRECIST v1.1 or iRECIST per investigator assessment • PFS by investigator assessment • CBR (CR + PR + stable disease) at 16 weeks
Phase 1: • Incidence of DLTs within the first 28 days of treatment with TNG462 as a single agent • Incidence of DLTs within the first 21 days of treatment with TNG462 plus pembrolizumab Phase 2: • ORR (CR + PR) as determined by RECIST v1.1, mRECIST v1.1, or iRECIST per investigator assessment • DOR as determined by RECIST v1.1, mRECIST v1.1 or iRECIST per investigator assessment • PFS by investigator assessment • CBR (CR + PR + stable disease) at 16 weeks
次要结局
- Phase 1: • ORR (CR + PR) as determined by RECIST v1.1, mRECIST v1.1 or iRECIST, per investigator assessment • DOR as determined by RECIST v1.1, mRECIST v1.1 or iRECIST,per investigator assessment • PFS by investigator assessment • CBR (CR + PR + stable disease) at 16 weeks for patients treated with single agent or at 18 weeks for patients treated with the pembrolizumab combination
- Phase 1 and 2: Type, frequency, severity, timing, and relationship to study treatment of any AEs, SAEs, and changes in vital signs, ECGs, and safety laboratory tests PK parameters of TNG462 Pre-treatment and trough pembrolizumab concentrations Changes in SDMA levels in tumor after dosing with TNG462
研究者
Kirsten Overoye-Chan
Scientific
Tango Therapeutics Inc.