TLN-372 for advanced KRAS‑mutant solid tumors

An Open-Label, Multicenter, Phase 1 Trial to Evaluate the Safety, Pharmacokinetics, and Anti-Tumor Activity of TLN-372 as a Single Agent and in Combination With Other Anti-Tumor Agents, in Patients With Advanced KRAS Mutant Solid Tumors

This trial will test whether the experimental drug TLN-372, alone or with cetuximab or pembrolizumab, is safe and can control advanced KRAS‑mutant solid tumors.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 240 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Treeline Biosciences, Inc. (Industry-sponsored)
• Locations: 11 sites (Birmingham, Alabama and 10 other locations)
• Trial ID: NCT07204340 on ClinicalTrials.gov

What this trial studies

This Phase 1 interventional study tests TLN-372 as a single agent and in combination with cetuximab or pembrolizumab in adults with locally advanced or metastatic KRAS‑mutant solid tumors. The primary goals are to define safety, pharmacokinetics, and preliminary anti‑tumor activity in patients with measurable disease, ECOG 0–1, and adequate organ function. Key exclusions include active brain metastases or CNS involvement, recent major surgery, significant cardiovascular disease, pregnancy or lactation, and conditions that could affect drug absorption. The trial is sponsored by Treeline Biosciences and is being conducted at U.S. cancer centers including Dana‑Farber, University of Alabama at Birmingham, and START Midwest.

Who should consider this trial

Good fit: Adults with measurable, locally advanced or metastatic KRAS‑mutant solid tumors who have ECOG performance status 0–1 and adequate organ function, and who are not pregnant and have no active CNS disease, are the intended participants.

Not a fit: Patients with active brain metastases or CNS involvement, significant cardiovascular or uncontrolled medical conditions, recent major surgery, pregnancy or lactation, or problems affecting drug absorption are unlikely to be eligible or to benefit.

Why it matters

Potential benefit: If successful, TLN-372 could provide a new targeted option to shrink or control tumors in patients with KRAS‑mutant cancers that have limited current therapies.

How similar studies have performed: Some KRAS‑targeted drugs (notably for G12C mutations) have shown clinical benefit, but broader KRAS targeting remains challenging and combination strategies with immunotherapy or EGFR inhibitors have shown only early promising signals.

Eligibility criteria

Inclusion Criteria:

1. Patients must have measurable disease at study entry.
2. Patients must have locally advanced or metastatic KRAS mutant solid tumors.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Adequate organ function.

Exclusion Criteria:

1. Patients must not have active brain metastases.
2. Patients must not have current or past history of central nervous system (CNS) involvement.
3. Patients must not have major surgery or severe trauma within 4 weeks prior to the start of the study.
4. Patients must not have any condition, including significant acute or chronic medical illness, active or uncontrolled infection, or the presence of laboratory abnormalities, that places patients at unacceptable risk of participating in this study.
5. Patients must not have clinically significant cardiovascular disease.
6. Pregnant or lactating.
7. Conditions that could affect drug absorption.

Where this trial is running

Birmingham, Alabama and 10 other locations

• University of Alabama at Birmingham — Birmingham, Alabama, United States (Recruiting)
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (Recruiting)
• START Midwest — Grand Rapids, Michigan, United States (Recruiting)
• Washington University Medical Campus — St Louis, Missouri, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (Recruiting)
• Sarah Cannon Research Institute — Nashville, Tennessee, United States (Recruiting)
• Peter MacCallum Cancer Centre — Melbourne, Victoria, Australia (Recruiting)
• Linear Clinical Research — Perth, Western Australia, Australia (Recruiting)
• Princess Margaret Cancer Centre — Toronto, Ontario, Canada (Recruiting)
• Hospital Universitary Vall d'Hebron — Barcelona, Spain (Recruiting)
• START Madrid_Hospital Universitario HM Sanchinarro_CIOCC — Madrid, Spain (Recruiting)

Study contacts

• Study coordinator: Treeline Clinical Operations

Conditions KRAS Mutant Solid Tumors; KRAS mutant solid tumors; KRAS