Dose escalation & expansion multi drug combos- mBRAF colorectal cancer
Research type
Research Study
Full title
A Phase Ib, multicenter, open-label dose escalation and expansion platform study of select drug combinations in adult patients with advanced or metastatic BRAF V600 colorectal cancer
IRAS ID
282328
Contact name
Michael Braun
Contact email
Sponsor organisation
Novartis Pharma AG
Eudract number
2019-004688-27
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 6 months, 22 days
Research summary
Summary of Research
This is an early phase oncology study, in which doublet and triplet treatment combinations are being evaluated in participants with advanced/metastatic colorectal cancer that carries a V600 BRAF mutation, which confers very poor prognosis. Participants will have not responded to, or have had their cancer progress on, available standard systemic therapy, with limited treatment options available to them. The study is comprised of a dose escalation part and may be followed by a dose expansion part for any combination treatment arm. The purpose is to assess the safety and tolerability of each treatment arm tested and identify recommended doses (RD) and regimens for future studies. This study will be undertaken in specialist cancer hospitals, worldwide.
Initially, potential participants will undergo assessments of their health and tests to confirm eligibility, including a fresh tumour biopsy. If eligible for the study, the participant will undergo 'cycles' of treatment, during which they will visit the study centre for safety assessments, evaluation of their cancer status etc. Some scans involve ionising radiation or exposure to radioactive substances.
Initially, the study will enrol participants into the DRB436+LTT462 doublet treatment arm 'backbone', to which partner investigational drugs will be added to comprise triplet combination treatment arms; +TNO155, TMT212, LXH254 OR PDR001. The starting dose of DRB436 + LTT462 in the triplet combinations will be at a lower dose level than already deemed safe and tolerable.
The dose escalation of the triplet combination treatment arms will start after criteria for the doublet arm are met. Multiple triplet combination treatment arms may enroll in parallel during dose escalation. Those treatment arms that reach a maximum tolerated dose (MTD)/recommended dose (RD) may, but are not required to, proceed to dose expansion to further explore safety, tolerability, and preliminary anti-tumor activity.
The participant will remain in the study whilst they still derive benefit from it.Summary of Results
The English lay summary will be available one year post global LPLV (25/09/2024). It will be available to PIs to share with patients and posted in the public domain on Novartis public website https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.novctrd.com%2F&data=05%7C02%7Ccambsandherts.rec%40hra.nhs.uk%7C2b059f895f9b42783d0c08ddf5c72210%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638936957844531968%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=kegCsPr%2FAJ0%2FpJSoLzncylXZzJTma%2F3tfdDg376LKiI%3D&reserved=0“
REC name
East of England - Cambridgeshire and Hertfordshire Research Ethics Committee
REC reference
20/EE/0145
Date of REC Opinion
16 Sep 2020
REC opinion
Further Information Favourable Opinion