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NCT06385925PHASE1, PHASE2Recruiting

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

Tyligand Pharmaceuticals (Suzhou) Limited

Start Date

4/29/2024

Completion Date

4/30/2027

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.

Detailed Description

Phase 1 Part of TSN1611 Monotherapy: The phase 1 part will evaluate the prespecified dose levels of TSN1611. Dose escalation will continue until up to the highest planned dose or the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is determined. Dose optimization could be performed as indicated by the emerging data. Phase 2 Part of TSN1611 Monotherapy: hase 2 part of TSN1611 monotherapy will evaluate the efficacy and safety of TSN1611 as monotherapy at the RP2D until disease progression or unacceptable toxicity in separate groups of patients with pancreatic cancer, colorectal cancer, non-small cell lung cancer, or other solid tumors, harboring KRAS G12D mutations. Phase 1b/2 Part of TSN1611 Combination Therapy: This part will consist of the investigations of 3 combined therapies (Cohort A, B and C). In each cohort, there will be a Phase 1b Safety Lead-in Stage to determine the dose of TSN1611 for the combination therapy (this part will be conducted in selected sites), followed by the Phase 2 Expansion Stage to enroll more subjects to determine the efficacy in different cohorts.

Eligibility Criteria

Age Range: 18 years to 75 years

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.

Interventions

DRUG

TSN1611

DRUG

TSN1611

DRUG

TSN1611

DRUG

TSN1611

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Conditions

Malignant Neoplasm

Locations

MD Anderson Cancer Center

Houston, Texas 77030

United States

NEXT Oncology

San Antonio, Texas 78229

United States

NEXT Virginia

Fairfax, Virginia 22031

United States

Anhui Provincial Cancer Hospital

Hefei, Anhui

China

Beijing Cancer Hospital

Beijing, Beijing Municipality

China

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong

China

Hubei Cancer Hospital

Wuhan, Hubei

China

Hunan Cancer Hospital

Changsha, Hunan

China

The First Affiliated Hospital of Nanchang University - Donghu District

Nanchang, Jiang

China

Linyi Cancer Hospital

Linyi, Shandong

China

Shanghai Tenth People's Hospital

Shanghai, Shanghai Municipality

China

West China Hospital, Sichuan University

Chengdu, Sichuan

China

Sir Run Run Shaw Hospital - Zhejiang University School of Med

Hangzhou, Zhejiang

China

The First Affiliated Hospital - Zhejiang University School of Medicine

Hangzhou, Zhejiang

China

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang

China

Taizhou Hospital of Zhejiang Province

Taizhou, Zhejiang

China

Beijing Cancer Hospital, Beijing, China

Beijing, 100142

China

Shanghai Chest Hospital, Shanghai, China

Shanghai, 200030

China

Shanghai Zhongshan Hospital, Shanghai, China

Shanghai, 200032

China