The FLOTILLA Study: Providing Continued Access to The Study Medicines Encorafenib and Binimetinib for Participants in Prior Clinical Trials

Study Overview
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Brief Summary
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The purpose of this clinical trial (called the FLOTILLA study) is to give continued access to the study medicines, as well as safety follow-up, for participants in prior clinical trials of encorafenib and/or binimetinib. All participants who took part in earlier encorafenib and/or binimetinib studies may participate the FLOTILLA study if they are still benefiting from the use of the study medicines. This will be determined by the study doctor. People may not participate in the FLOTILLA study if they have not enrolled in a prior study of encorafenib or binimetinib. Participants that had enrolled but had stopped receiving the study treatment in a prior study cannot enrolled in this study. Participants in the FLOTILLA study will receive encorafenib and/or binimetinib at the same dose and frequency as in their prior study, for up to about 5 years.

Detailed Description
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This is an open-label, continuation study for participants receiving study intervention(s) in an encorafenib/binimetinib Parent Study. The study is being conducted under a Master Protocol for Encorafenib/Binimetinib Continuation Sub-Studies with an individual encorafenib/binimetinib continuation sub-study protocol for each eligible Parent Study. Approximately 75 participants from potentially qualifying Parent Studies will be included in this Encorafenib/Binimetinib Continuation study. This continuation study includes multiple sub-study protocols to allow participants from each of the following parent studies: C4211001 - NCT01320085; C4211003 - NCT01849874; C4221003 - NCT03864042; C4221005 - NCT01543698; C4221006 - NCT03911869; C4221009 - NCT02928224; C4221010 - NCT01436656; C4221013 - NCT02159066; ANCHOR-CRC - NCT03693170

Official Title
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ENCORAFENIB/BINIMETINIB MASTER PROTOCOL: AN OPEN-LABEL CONTINUATION STUDY FOR PARTICIPANTS CONTINUING FROM ENCORAFENIB/BINIMETINIB CLINICAL STUDIES

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: Binimetinib only treatment
* Drug: Encorafenib only Treatment
* Drug: Encorafenib & Binimetinib Treatment
* Drug: Treatment of Encorafenib & Binimetinib & Ribociclib
* Drug: Treatment of Encorafenib & Binimetinib & Cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any participant who is receiving study intervention and deriving clinical benefit (as determined by the principal investigator) in an encorafenib/binimetinib Parent Study, with no ongoing NCI CTCAE version 4.03 Grade ≥3 or intolerable Grade 2 AEs considered to be related to study treatment. Participants must agree to follow the reproductive criteria as outlined in the applicable Encorafenib/Binimetinib Continuation Sub-Study Protocol. Exclusion Criteria: Any medical reason that, in the opinion of the investigator or sponsor, precludes the participant from inclusion in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Each participant will continue to receive the same study treatment regimen at the same dose level as that received in the Parent Studies. The details of study intervention and duration of treatment are specified in the applicable Encorafenib/Binimetinib Continuation Sub-Study Protocol.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Binimetinib only treatment<br>For those participants receiving binimetinib treatment in parent studies | Drug: Binimetinib only treatment<br>* Binimetinib will be administered at the same dose level (15 mg to 45 mg) as that received in the Parent Studies C4211001 and C4211003 with water irrespective of food, continuously, starting on Day 1.<br>|
| Experimental: Encorafenib only Treatment<br>For those participants receiving encorafenib only treatment in parent studies | Drug: Encorafenib only Treatment<br>* Encorafenib will be self-administered at the same dose level as that received in the C4221010 Parent Study.<br>|
| Experimental: Encorafenib & Binimetinib Treatment<br>For those participants receiving encorafenib & binimetinib treatment in parent studies. | Drug: Encorafenib & Binimetinib Treatment<br>* Encorafenib will be administered on a 300 mg QD schedule and binimetinib will be administered on a 45 mg BID schedule, both orally as a flat fixed dose. Cetuximab will be administered at either 400 mg/m2 or 500 mg/m2 IV every 2 weeks on Days 1 and 15 of every cycle.<br>|
| Experimental: Treatment of Encorafenib & Binimetinib & Ribociclib<br>For those participants receiving treatment of encorafenib & binimetinib & ribociclib in parent studies | Drug: Treatment of Encorafenib & Binimetinib & Ribociclib<br>* Encorafenib capsule and ribociclib capsules or tablets will be co-administered orally QD with binimetinib tablets BID. The study drugs will be administered as a flat-fixed dose, and not by body weight or body surface area.<br>|
| Experimental: Treatment of Encorafenib & Binimetinib & Cetuximab<br>For those participants receiving treatment of encorafenib & binimetinib & cetuximab in parent studies | Drug: Treatment of Encorafenib & Binimetinib & Cetuximab<br>* Encorafenib will be administered on a 300 mg QD schedule and binimetinib will be administered on a 45 mg BID schedule, both orally as a flat fixed dose. Cetuximab will be administered at either 400 mg/m2 or 500 mg/m2 IV every 2 weeks on Days 1 and 15 of every cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events leading to permanent discontinuation of study intervention |  | Baseline up to approximately 5 years | 
| Number serious adverse events reported for all participants |  | Baseline up to approximately 5 years |