Clinical trial NCT06385925: A Study of TSN1611 Treating Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation
Official title: Phase 1/2 Study of TSN1611 in Subjects With Advanced Solid Tumors Harboring KRAS G12D Mutation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Malignant Neoplasm
Keywords: solid tumor
KRAS G12D mutation
pancreatic cancer
colorectal cancer
non-small cell lung cancer
malignant neoplasm
Lead sponsor: Tyligand Pharmaceuticals (Suzhou) Limited
Sponsor class: INDUSTRY
First posted: 2024-04-26
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose limiting toxicities (DLTs) in phase 1 part
timeFrame: 21 days
measure: Objective response rate (ORR) in phase 2 part
timeFrame: Up to 3 years
Secondary outcomes:
measure: Adverse events
timeFrame: Up to 3 years
measure: Area under the plasma concentration-time curve (AUC)
timeFrame: 9 weeks
measure: Maximum blood concentrations (Cmax)
timeFrame: 9 weeks
measure: Time to maximum blood concentration (Tmax)
timeFrame: 9 weeks
measure: Duration of response (DOR)
timeFrame: Up to 3 years
measure: Time to response (TTR)
timeFrame: Up to 3 years
measure: Disease control rate (DCR)
timeFrame: Up to 3 years
measure: Progression free survival (PFS)
timeFrame: Up to 3 years
measure: Overall survival
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
city: Beijing
country: China
facility: Beijing Cancer Hospital, Beijing, China
city: Shanghai
country: China
facility: Shanghai Chest Hospital, Shanghai, China
city: Shanghai
country: China
facility: Shanghai Zhongshan Hospital, Shanghai, China
Study officials:
affiliation: Tyligand Bioscience (Shanghai) Limited
name: Cindy Li
role: STUDY_DIRECTOR
References: