Treatment for advanced solid tumors with KRAS G12D mutation

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

This study is testing a new drug called TSN1611 to see if it can safely help people with advanced solid tumors that have a specific KRAS G12D mutation.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 440 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Tyligand Pharmaceuticals (Suzhou) Limited (Industry-sponsored)
• Drugs / interventions: radiation, cetuximab
• Locations: 19 sites (Houston, Texas and 18 other locations)
• Trial ID: NCT06385925 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of TSN1611 in patients with advanced solid tumors that have the KRAS G12D mutation. It consists of a phase 1 dose escalation to determine the maximum tolerated dose, followed by a phase 2 evaluation of the drug's effectiveness as a monotherapy in specific cancer types, including pancreatic, colorectal, and non-small cell lung cancer. The study is open-label and multi-center, allowing for a diverse patient population. Participants will be monitored for safety and treatment response throughout the trial.

Who should consider this trial

Good fit: Ideal candidates are adults with advanced solid tumors that have the KRAS G12D mutation and have exhausted standard treatment options.

Not a fit: Patients with active central nervous system metastases or leptomeningeal disease will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors harboring the KRAS G12D mutation.

How similar studies have performed: Other studies targeting KRAS mutations have shown promise, indicating potential for success with this novel approach.

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.≤ 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.

Where this trial is running

Houston, Texas and 18 other locations

• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• NEXT Oncology — San Antonio, Texas, United States (Recruiting)
• NEXT Virginia — Fairfax, Virginia, 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, China (Recruiting)
• Shanghai Chest Hospital, Shanghai, China — Shanghai, China (Recruiting)
• Shanghai Zhongshan Hospital, Shanghai, China — Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Tyligand Clinical Trial Info

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