A Study of TSN1611 Treating Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation

Summary

The study is a first-in-human (FIH), open-label, multi-center phase 1/2 study of TSN1611 in subjects with KRAS G12D mutant advanced solid tumors. This study will consist of a phase 1 dose escalation part and phase 2 dose expansion part. This study will evaluate the efficacy of TSN1611 at RP2D(s) through ORR using RECIST version 1.1, and determine and confirm the MTD/RP2D for TSN1611 in combination with cetuximab, in combination with cetuximab and mFOLFOX6, in combination with gemcitabine and albumin-bound paclitaxel in subjects with selected solid tumors.

Interventions

• TSN1611 · DRUG

  TSN1611 will be administered at the assigned dose level, orally, until disease progression or intolerable toxicity.

• TSN1611 · DRUG

  TSN1611 BID, Cetuximab will be administered via intravenous infusion at a dose of 500 mg/m² every 2 weeks.

• TSN1611 · DRUG

  TSN1611 BID, Paclitaxel (albumin-bound) at 125 mg/m² and gemcitabine at 1000 mg/m² will be administered via intravenous infusion on Days 1, 8, and 15 of each 4-week cycle.

• TSN1611 · DRUG

  TSN1611 BID everyday and Patients will be administered with mFOLFOX6 on Days 1 and 2, every 2 weeks.

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

Subjects must meet all the following inclusion criteria to be eligible for participation in this study:

* The subject fully understands the requirements of the study and voluntarily signs the ICF.
* At least 18 years of age at the time of informed consent.≤ 75 years of age for Cohort B and C.
* Life expectancy of 3 months or more.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
* Phase 1 part (1a/1b) of Monotherapy:

Subjects with histologically or cytologically confirmed locally advanced or metastatic solid tumor harboring KRAS G12D mutation; subjects must be refractory or intolerable to standard treatment, or have no standard treatment available, or the subject is ineligible or declines standard treatment.

Phase 2 part of TSN1611 Monotherapy:

Subjects with histologically or cytologically confirmed locally advanced or metastatic PDAC、CRC and NSCLC harboring KRAS G12D mutation; According to the requirements of different combined cohorts, the number of previous treatments is taken into account.

• Patients with adequate cardiac, liver, renal function, etc.

Exclusion Criteria

Subjects will be excluded if they meet any of the following criteria:

* Leptomeningeal disease or Active central nervous system (CNS) metastases.
* Prior systemic anti-cancer treatment within 21 days or 5 half-lives (whichever is shorter will be used as the criteria) prior to the first dose of study drug.
* Radical radiation within 4 weeks prior to the first dose of study drug; palliative radiotherapy within 1 week prior to the first dose of study drug.
* Any unresolved Grade 2 or higher toxicity from previous anticancer therapy except alopecia.
* Has participated in a study of investigational agent and received the investigational agent within 21 days or 5 half-lives, if known (whichever is shorter) prior to the first dose of study drug.
* History of interstitial lung disease (ILD), drug induced IDL, or current active pneumonitis, radiation pneumonitis requiring therapeutic intervention, or uncontrolled other lung disease.
* Any of the following in the past 6 months: myocardial infarction, unstable angina, symptomatic congestive heart failure, stroke or transient ischemic attack, pulmonary embolism.
* Prior treatment with KRAS G12D targeted therapy.
* Has a history or current evidence of any severe condition, concurrent therapy, or laboratory abnormality that might confound the interpretation of the study results, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the investigator.

Sites (19)

• MD Anderson Cancer Center, Houston, Texas · RECRUITING
• NEXT Oncology, San Antonio, Texas · RECRUITING
• NEXT Virginia, Fairfax, Virginia · RECRUITING
• Anhui Provincial Cancer Hospital, Hefei, Anhui, China · RECRUITING
• Beijing Cancer Hospital, Beijing, Beijing Municipality, China · RECRUITING
• The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China · RECRUITING
• Hubei Cancer Hospital, Wuhan, Hubei, China · RECRUITING
• Hunan Cancer Hospital, Changsha, Hunan, China · RECRUITING
• The First Affiliated Hospital of Nanchang University - Donghu District, Nanchang, Jiang, China · RECRUITING
• Linyi Cancer Hospital, Linyi, Shandong, China · RECRUITING
• Shanghai Tenth People's Hospital, Shanghai, Shanghai Municipality, China · RECRUITING
• West China Hospital, Sichuan University, Chengdu, Sichuan, China · RECRUITING
• Sir Run Run Shaw Hospital - Zhejiang University School of Med, Hangzhou, Zhejiang, China · RECRUITING
• The First Affiliated Hospital - Zhejiang University School of Medicine, Hangzhou, Zhejiang, China · RECRUITING
• The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China · RECRUITING
• Taizhou Hospital of Zhejiang Province, Taizhou, Zhejiang, China · RECRUITING
• Beijing Cancer Hospital, Beijing, China, Beijing, China · RECRUITING
• Shanghai Chest Hospital, Shanghai, China, Shanghai, China · RECRUITING
• Shanghai Zhongshan Hospital, Shanghai, China, Shanghai, China · RECRUITING