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

Study Overview

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

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.

Phase 1 Part: 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: Phase 2 part will evaluate the efficacy and safety of TSN1611 as monotherapy at the recommended dose in separate groups of patients with pancreatic cancer, colorectal cancer, non-small cell lung cancer, or other solid tumors, harboring KRAS G12D mutations.

Malignant Neoplasm

DRUG: TSN1611

TSN1611-2023-101

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2024-04-18	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-03-19
First Submitted that Met QC Criteria 2024-04-23	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-03-24
First Posted (ACTUAL) 2024-04-26	Results First Posted N/A	Last Verified 2025-03

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Phase 1: Dose-finding/evaluation of TSN1611 monotherapy 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 TSN1611 will be administered at the assigned dose level, orally, until disease progression or intolerable toxicity.
EXPERIMENTAL: Phase 2: Dose expansion of TSN1611 monotherapy 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 mut	DRUG: TSN1611 TSN1611 will be administered at the assigned dose level, orally, until disease progression or intolerable toxicity.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Phase 1: Dose-finding/evaluation of TSN1611 monotherapy

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

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

EXPERIMENTAL: Phase 2: Dose expansion of TSN1611 monotherapy

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 mut

DRUG: TSN1611

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

Primary Outcome Measures	Measure Description	Time Frame
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 Outcome Measures	Measure Description	Time Frame
Adverse events	To assess the safety profile and tolerability of TSN1611 as monotherapy in subjects with KRAS G12D mutant advanced solid tumors.	Up to 3 years
Area under the plasma concentration-time curve (AUC)	To characterize the pharmacokinetic (PK) profile of TSN1611.	9 weeks
Maximum blood concentrations (Cmax)	To characterize the PK profile of TSN1611.	9 weeks
Time to maximum blood concentration (Tmax)	To characterize the PK profile of TSN1611.	9 weeks
Duration of response (DOR)	To evaluate the anti-tumor activity of TSN1611 using RECIST version 1.1.	Up to 3 years
Time to response (TTR)	To evaluate the anti-tumor activity of TSN1611 using RECIST version 1.1.	Up to 3 years
Disease control rate (DCR)	To evaluate the anti-tumor activity of TSN1611 using RECIST version 1.1.	Up to 3 years
Progression free survival (PFS)	To evaluate the anti-tumor activity of TSN1611 using RECIST version 1.1.	Up to 3 years
Overall survival		Up to 3 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Tyligand Clinical Trial Info

Phone Number: +86 021-50720081

Email: clinical_trial@tyligand.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.
Life expectancy of 3 months or more.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
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, etc.
Patients with adequate cardiac, liver, renal function, etc.

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Cindy Li, Tyligand Bioscience (Shanghai) Limited

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Clinical Trial Record