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

Malignant Neoplasm Clinical Trial

Official title:

Phase 1/2 Study of TSN1611 in Subjects With Advanced Solid Tumors Harboring KRAS G12D Mutation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06385925
• Other study ID #: TSN1611-2023-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 30, 2024
• Est. completion date: April 30, 2027

Study information

• Verified date: April 2024
• Source: Tyligand Bioscience (Shanghai) Limited
• Contact: Cindy Li
• Phone: +86 021-50720081
• Email: li_jing_cindy[@]tyligand.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: April 30, 2027
• Est. primary completion date: October 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.
• 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. 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.

Related Conditions & MeSH terms

• Malignant Neoplasm
• Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	NEXT Virginia	Fairfax	Virginia
United States	MD Anderson Cancer Center	Houston	Texas
United States	NEXT Oncology	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Tyligand Bioscience (Shanghai) Limited

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Area under the plasma concentration-time curve (AUC)	To characterize the pharmacokinetic (PK) profile of TSN1611.	9 weeks
Secondary	Maximum blood concentrations (Cmax)	To characterize the PK profile of TSN1611.	9 weeks
Secondary	Time to maximum blood concentration (Tmax)	To characterize the PK profile of TSN1611.	9 weeks
Secondary	Duration of response (DOR)	To evaluate the anti-tumor activity of TSN1611 using RECIST version 1.1.	Up to 3 years
Secondary	Time to response (TTR)	To evaluate the anti-tumor activity of TSN1611 using RECIST version 1.1.	Up to 3 years
Secondary	Disease control rate (DCR)	To evaluate the anti-tumor activity of TSN1611 using RECIST version 1.1.	Up to 3 years
Secondary	Progression free survival (PFS)	To evaluate the anti-tumor activity of TSN1611 using RECIST version 1.1.	Up to 3 years
Secondary	Overall survival		Up to 3 years