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
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 20
- Locations
- 2
- Primary Endpoint
- Number of patients experiencing adverse events (AEs) that meet protocol-defined dose-limiting toxicity (DLT) criteria following administration of TLN-372
Study Overview
Brief Summary
Part 1: To evaluate the safety and tolerability of TLN-372 in patients with locally advanced or metastatic KRAS mutant solid tumors and to estimate the maximum tolerated dose of TLN-372 as a single agent.
Part 2: To evaluate the anti-tumor activity of TLN-372 as a single agent in patients with locally advanced or metastatic KRAS mutant solid tumors, to evaluate the anti-tumor activity of TLN-372 in combination with cetuximab and to evaluate the safety of TLN-372 in combination with pembrolizumab.
Eligibility Criteria
- Ages
- 18 years to 65+ years (18-64 Years, 65+ Years)
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •At least 18 years of age at the time of signing the informed consent form (ICF).
- •Patients must have locally advanced or metastatic KRAS mutant solid tumors
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate organ function
Exclusion Criteria
- •Patients must not have active brain metastases
- •Patients must not have current or past history of central nervous system (CNS) disease
- •Patients must not have major surgery or severe trauma within 4 weeks prior to the first dose of the study drug
- •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
- •Patients must not have clinically significant cardiovascular disease.
- •Pregnant or lactating
- •Conditions that could affect drug absorption
Outcomes
Primary Outcomes
Number of patients experiencing adverse events (AEs) that meet protocol-defined dose-limiting toxicity (DLT) criteria following administration of TLN-372
Number of patients experiencing adverse events (AEs) that meet protocol-defined dose-limiting toxicity (DLT) criteria following administration of TLN-372
Incidence and severity of Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) leading to dose modification and discontinuation.
Incidence and severity of Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) leading to dose modification and discontinuation.
Anti-tumor activity of TLN-372 by evaluating the objective response rate (ORR) according to the RESIST v1.1
Anti-tumor activity of TLN-372 by evaluating the objective response rate (ORR) according to the RESIST v1.1
Secondary Outcomes
- Maximum observed plasma concentration (Cmax), time to peak drug concentration (Tmax), Minimum observed plasma concentration (Cmin), and Area Under the Plasma Concentration-Time Curve (AUC) of TLN-372
- Anti-tumor activity of TLN-372 by evaluating the duration of response (DOR) as assessed by the time from the date of first objective response to the date of disease progression
- Frequency of dose interruptions, reductions and dose intensity
- Clinically significant ECG QT interval from baseline assessed as per NCI CTCAE v5.0
- Clinically significant laboratory abnormalities from baseline in safety laboratory test results, assessed as per NCI CTCAE v5.0
Investigators
Treeline Clinical Operations
Scientific
Treeline Biosciences Inc.