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

NCT06385925 | Recruiting Phase 1 FDA Drug

• 1 other identifier: TSN1611-2023-101
• Study Type: interventional
• Target: 440
• Locations: 2 countries
• Sites: 19

Brief 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.

Conditions

Malignant Neoplasm

Keywords

solid tumor; KRAS G12D mutation; pancreatic cancer; colorectal cancer; non-small cell lung cancer; malignant neoplasm

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicities (DLTs) in phase 1 part

  To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose(s) (RP2D\[s\]) of TSN1611 as monotherapy in subjects with KRAS G12D mutant advanced solid tumors.

  21 days

• Objective response rate (ORR) in phase 2 part

  To evaluate the anti-tumor activity of TSN1611 using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

  Up to 3 years

Secondary Outcomes (9)

• Adverse events

  Up to 3 years

• Area under the plasma concentration-time curve (AUC)

  9 weeks

• Maximum blood concentrations (Cmax)

  9 weeks

• Time to maximum blood concentration (Tmax)

  9 weeks

• Duration of response (DOR)

  Up to 3 years

Study Arms (5)

Phase 1: Dose-finding/evaluation of TSN1611 monotherapy

EXPERIMENTAL

The phase 1 part will evaluate the prespecified sequential dose levels of TSN1611 in subjects with KRAS G12D mutant advanced solid tumors to determine the recommended dose of TSN1611 for further investigation.

Drug: TSN1611

Phase 2: Dose expansion of TSN1611 monotherapy

EXPERIMENTAL

Phase 2 part will evaluate the efficacy and safety of TSN1611 as monotherapy at the recommended dose level in separate groups of patients with pancreatic cancer, colorectal cancer, non-small cell lung cancer, or other solid tumors, harboring KRAS G12D mutations.

Drug: TSN1611

Dose of Phase 1b/2 part of TSN1611 combination therapy-Cohort A

EXPERIMENTAL

Cohort A: TSN1611 combined with cetuximab treating subjects with advanced solid tumors harboring KRAS G12D mutation:

Drug: TSN1611

Dose of Phase 1b/2 part of TSN1611 combination therapy-Cohort B

EXPERIMENTAL

Cohort B: TSN1611 combined with GnP regimen (i.e., gemcitabine and nab-paclitaxel) treating subjects with advanced PDAC with KRAS G12D mutation who received no prior systemic treatment in the advanced setting.

Drug: TSN1611

Dose of Phase 1b/2 part of TSN1611 combination therapy-Cohort C

EXPERIMENTAL

Cohort C: TSN1611 combined with cetuximab and mFOLFOX6 regimen (i.e., fluorouracil, leucovorin, oxaliplatin) treating subjects with advanced CRC with KRAS G12D mutation who received no prior systemic treatment in the advanced setting.

Drug: TSN1611

Interventions

TSN1611 DRUG

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

Phase 1: Dose-finding/evaluation of TSN1611 monotherapy; Phase 2: Dose expansion of TSN1611 monotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tyligand Pharmaceuticals (Suzhou) Limited: lead

Study Sites (19)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

NEXT Oncology

San Antonio, Texas, 78229, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031, United States

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, 100142, China

RECRUITING

Shanghai Chest Hospital, Shanghai, China

Shanghai, 200030, China

RECRUITING

Shanghai Zhongshan Hospital, Shanghai, China

Shanghai, 200032, China

RECRUITING

MeSH Terms

Conditions

Neoplasms; Pancreatic Neoplasms; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Taxes; Oxaliplatin; Fluorouracil; Leucovorin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations; Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Cindy Li

  Tyligand Bioscience (Shanghai) Limited

  STUDY DIRECTOR

Central Study Contacts

Tyligand Clinical Trial Info

CONTACT

+86 021-50720081; clinical_trial@tyligand.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2024
• First Posted: April 26, 2024
• Study Start: April 29, 2024
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): April 30, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); CN (16)