None listed
Conditions
Brief summary
The primary purpose of this study is to evaluate the safety, pharmacokinetics, and anti-tumour activity of TLN-372 in combination with cobicistat, in patients with advanced KRAS mutant solid tumours. Who is it for? You may be eligible for this study if you are male or female, at least 18 years of age, have measurable locally advanced or metastatic KRAS mutant solid tumours at study entry, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate organ function. Study details All eligible participants will receive TLN-372 in combination with cobicistat. Patients will be monitored with clinical visits, blood tests, and radiology images. It is hoped that the result of this study will show if TLN-372 is safe when taken with a helper medication, cobicistat, show if cobicistat interacts with TLN-372 and understand the effects of this interaction on the body, understand how the body absorbs, distributes, breaks down, and gets rid of TLN-372 when given with cobicistat, and show if TLN-372 has the possibility of helping treat patients with advanced solid tumours with a KRAS mutation. This research will hopefully help further the development of TLN-372 to improve the treatment for patients with KRAS mutant cancers.
Interventions
This is a Phase I dose escalation study of two treatments, TLN-372 co-administered with cobicistat (a CYP3A inhibitor approved in Australia in combination with medicines other than TLN-372), in patients with locally advanced metastatic G12D, G12V, G12C, G12S, G12A, G13C and G13D KRAS mutant solid tumours and KRAS WT amplified solid tumours.
Cobicistat will be administered continuously as an oral tablet at a fixed dose of 150 mg once daily.
TLN-372 will be administered as an oral tablet eithe
This is a Phase I dose escalation study of two treatments, TLN-372 co-administered with cobicistat (a CYP3A inhibitor approved in Australia in combination with medicines other than TLN-372), in patients with locally advanced metastatic G12D, G12V, G12C, G12S, G12A, G13C and G13D KRAS mutant solid tumours and KRAS WT amplified solid tumours. Cobicistat will be administered continuously as an oral tablet at a fixed dose of 150 mg once daily. TLN-372 will be administered as an oral tablet either once daily (QD) or twice daily (BID) continuously in 21-day cycles with no rest period between cycles. Patients will be enrolled into sequential dose-escalation cohorts depending on safety and tolerability experienced by patients during the study. Approximately 6 dose-escalation cohorts are expected. The starting dose of TLN372 is 12.5 mg once daily (QD). Subsequent cohorts will escalate to higher doses and could range from 12.5mg to 200mg (QD or BID) as determined by safety, tolerability, and pharmacokinetics experienced. Treatment will continue until disease progression, death, intolerable toxicity, withdraw of consent, or the completion or termination of the study, whichever occurs first. A dosing diary will record administration of the pills and there will be accountability records to keep track of drug supply.
Sponsors
Treeline Biosciences, Inc.
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion Criteria: Patients must have measurable disease at study entry. 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
Active brain metastases. Current or past history of central nervous system (CNS) involvement. Major surgery or severe trauma within 4 weeks prior to the start of the study. 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. Clinically significant cardiovascular disease. Pregnant or lactating. Known or suspected hypersensitivity to TLN-372 or cobicistat, or their excipients. Conditions that could affect drug absorption.
Outcome results
None listed