A study of safety and efficacy of novel targeted therapy combinations in adult patients with advanced or metastatic colorectal cancer.
- Conditions
- Advanced or metastatic BRAF V600 colorectal cancer.
- Interventions
- Registration Number
- 2023-510379-77-00
- Lead Sponsor
- Novartis Pharma AG
- Brief Summary
A phase Ib, open-label platform study of select drug combinations chosen in order to characterize safety and tolerability of each treatment arm tested and to identify recommended doses and regimens for future studies.
- Detailed Description
This is a phase Ib, multi-center, open-label study with multiple treatment arms in adult patients with advanced or metastatic BRAF V600 (E, D, or K) in order to characterize safety and tolerability of each treatment arm tested and to identify recommended doses and regimens for future studies. The open platform design of this study is adaptive to allow removal of combination treatment arm(s) based on emerging data and facilitate introduction of new candidate combinations. The study is comprised of a dose escalation part and may be followed by a dose expansion part for any combination treatment arm.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Not specified
- Target Recruitment
- 35
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dabrafenib + LTT462 backbone arm 1 LTT462 dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer Dabrafenib + LTT462 + trametinib triplet arm 1 LTT462 dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer Dabrafenib + LTT462 + LXH254 triplet arm 2 LXH254 dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer - Arm is closed for further enrollment. Dabrafenib + LTT462 + TNO155 triplet arm 3 TNO155 dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer Dabrafenib + LTT462 + spartalizumab triplet arm 4 LTT462 dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer - Arm is closed for further enrollment. Dabrafenib + trametinib + TNO155 triplet arm 5 TNO155 dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer Dabrafenib + LTT462 + Tislelizumab triplet arm 6 LTT462 dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer Dabrafenib + LTT462 + LXH254 triplet arm 2 LTT462 dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer - Arm is closed for further enrollment. Dabrafenib + LTT462 + TNO155 triplet arm 3 LTT462 dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer Dabrafenib + LTT462 + trametinib triplet arm 1 Dabrafenib dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer Dabrafenib + LTT462 backbone arm 1 Dabrafenib dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer Dabrafenib + LTT462 + trametinib triplet arm 1 Trametinib dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer Dabrafenib + LTT462 + LXH254 triplet arm 2 Dabrafenib dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer - Arm is closed for further enrollment. Dabrafenib + LTT462 + TNO155 triplet arm 3 Dabrafenib dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer Dabrafenib + LTT462 + spartalizumab triplet arm 4 Dabrafenib dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer - Arm is closed for further enrollment. Dabrafenib + trametinib + TNO155 triplet arm 5 Dabrafenib dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer Dabrafenib + LTT462 + spartalizumab triplet arm 4 Spartalizumab dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer - Arm is closed for further enrollment. Dabrafenib + trametinib + TNO155 triplet arm 5 Trametinib dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer Dabrafenib + LTT462 + Tislelizumab triplet arm 6 Dabrafenib dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer Dabrafenib + LTT462 + Tislelizumab triplet arm 6 Tislelizumab dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
- Primary Outcome Measures
Name Time Method Incidence and nature of dose limiting toxicities (DLTs) in the first cycle 30 months To characterize safety and tolerability of each treatment arm tested and identify recommended doses (RD) and regimens for future studies
Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs, and ECGs 34 months To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies
Frequency of dose interruptions 30 months To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies
Frequency of dose reductions 30 months To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies
Dose intensity 30 months To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies
- Secondary Outcome Measures
Name Time Method AUClast derived from Serum/plasma concentration of individual investigational drugs within combination treatments 30 months To characterize the PK of each investigational drug within each treatment arm
Best overall response (BOR) 34 months To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
Progression free survival (PFS) 34 months To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
Overall response rate (ORR) 34 months To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
Duration of response (DOR) 34 months To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
Disease control rate (DCR) 34 months To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
Change from baseline of the PD marker DUSP6 in tumor tissue (dose escalation only) 30 months To evaluate PD effect in their respective combinations in tumor
AUCtau derived from Serum/plasma concentration of individual investigational drugs within combination treatments 30 months To characterize the PK of each investigational drug within each treatment arm
Cmax derived from Serum/plasma concentration of individual investigational drugs within combination treatments 30 months To characterize the PK of each investigational drug within each treatment arm
Tmax derived from Serum/plasma concentration of individual investigational drugs within combination treatments 30 months To characterize the PK of each investigational drug within each treatment arm
Trial Locations
- Locations (5)
University of California LA Santa Monica Location
🇺🇸Los Angeles, California, United States
Massachusetts General Hospital Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Sarah Cannon Research Institute SC
🇺🇸Nashville, Tennessee, United States
Uni Of TX MD Anderson Cancer Cntr
🇺🇸Houston, Texas, United States
Novartis Investigative Site
🇬🇧Manchester, United Kingdom
University of California LA Santa Monica Location🇺🇸Los Angeles, California, United States