Encorafenib/binimetiib master protocol: an open-label continuation study for participants continuing from encorafenib/binimetinib clinical studies. ;Sub-study 1:
An open-label study for continued treatment access for participants from the C4211001 (Array CMEK162X2201) and the C4211003 (Array-162-311, MILO) Binimetinib studies.;Sub-study 2:
An open-label study for continued treatment access for participants from the C4221004 (Array CMEK162B2301, Columbus) Encorafenib and Binimetinib study;Sub-s

Sub-study 1:

The C4211001 Parent Study was a Phase 2, open-label study to assess the safety
and efficacy of binimetinib (also known as MEK162) in adults with locally
advanced and unresectable or metastatic malignant cutaneous melanoma, harboring
BRAFV600 or NRAS mutations. The PCD was reached on 07 January 2014. Two
participants remained on binimetinib treatment
in the Parent Study as of 30 September 2021.

The C4211003 Parent Study was a multinational, randomized, open-label Phase 3
study to evaluate binimetinib versus physician*s choice of selected
chemotherapies in participants with LGS carcinomas of the ovary, fallopian tube
or primary peritoneum who had recurrent
or persistent disease following at least 1 prior platinum-based chemotherapy
treatment and no more than 3 prior lines of chemotherapy. The PCD was reached
on 20 January 2016.
Two participants remained on binimetinib treatment in the Parent Study as of 30
September
2021.

Participants who are deriving benefit from study intervention as determined by
the respective investigator may continue to receive treatment on this
Continuation Sub-Study. All
The ongoing participants in the Parent Studies are receiving treatment with
binimetinib; thus, this protocol only describes the procedures for study
intervention of binimetinib. The investigator is to follow the guidance below
for the conduct of this Continuation Study.

Sub-study 2:

The C4221004 Parent Study was a 2-part, multi-center, randomized, open-label,
Phase 3 study comparing the efficacy and safety of encorafenib plus binimetinib
to vemurafenib and encorafenib monotherapy in participants with locally
advanced unresectable or metastatic melanoma with BRAFV600 mutation. Part 1 of
the study evaluated the activity of Combo 450 (encorafenib 450 mg QD plus
binimetinib 45 mg BID). Part 2 further defined the contribution of binimetinib
to the combination using a lower encorafenib dose, 300 mg QD, in the
combination. PCD was achieved on 09 November 2016. As of 28 March 2022, 62
participants are on active treatment, including 30 participants in Part 1 and
32 participants in Part 2.
Participants who are deriving benefit from study intervention as determined by
the respective investigator may continue to receive treatment on this
Continuation Sub-Study. This protocol only describes the procedures for these
potential participants from the parent study. The rollover of eligible
participants to this Continuation Sub-Study will occur when 80% of randomized
participants in each part of the study have died, withdrawn consent for
survival follow-up, or are lost to follow-up, as needed for the final OS update
to be performed in the parent study.

Sub-study 3:
The C4221008 Parent Study was an open-label, multicenter, non-randomized, Phase
2 study to determine the safety, tolerability and efficacy of encorafenib given
in combination with binimetinib in treatment-naïve and previously treated
participants with BRAF V600E-mutant metastatic NSCLC. Participants who are
deriving benefit from study intervention(s) as determined by the respective
investigator may continue to receive treatment on this Continuation Sub-Study.
This protocol only describes the procedures for these potential participants
from the Parent Study.

This study has been transitioned to CTIS with ID 2023-509408-13-00 check the CTIS register for the current data.

- To monitor the safety and tolerability of binimetinib
- To monitor the safety and tolerability of encorafenib

As an Encorafenib/Binimetinib Continuation Sub-Study, this study does not have
a separate design apart from what has been described in the Master Protocol for
Encorafenib/Binimetinib Continuation Sub-Studie:

This is an open-label, master protocol for encorafenib/binimetinib continuation
sub-studies for participants receiving study intervention(s) in an
encorafenib/binimetinib Parent Study. The study is being conducted under this
Master Protocol for Encorafenib/Binimetinib Continuation Sub-Studies with an
individual encorafenib/binimetinib continuation sub-study protocol for each
eligible Parent Study (see Section 4.1.1).

Approximately 75 participants from potentially qualifying Parent Studies will
be included in this Master Protocol for Encorafenib/Binimetinib Continuation
Sub-Studies.

The following terminology will be used throughout this protocol:
• Master Protocol for Encorafenib/Binimetinib Continuation Sub-Studies:
Includes a description of study procedures and assessments that are to be
performed for all participants. • Parent Study: original
encorafenib/binimetinib study meeting the criteria provided in Section 4.1.1.
• Encorafenib/Binimetinib Continuation Sub-Study Protocol: Includes the
specific aspects of the respective Parent Study, which includes and is not
limited to, schedule of activities, dosing, toxicity management, dose
modification, drug storage/handling, and additional safety data collection (if
required).

4.1.1. Qualified Studies for This Protocol
For inclusion in this Master Protocol for Encorafenib/Binimetinib Continuation
Sub-Studies, the Parent Study must be an encorafenib/binimetinib study, with
adequate drug supply of the investigational product for clinical use, and which
meets at least one of the following criteria:
• The main analyses, at minimum primary analysis, have been completed as
defined by the encorafenib/binimetinib Parent Study.
• Study was terminated early following a population level futility analysis or
sponsor business decision, and the study intervention for the proposed
indication is not otherwise available outside of a clinical study for
individual participants who may continue to derive clinical benefit from the
treatment as determined by the principal investigator.

For more information, please refer to the master protocol, dated 03Nov2021

Oral administration of binimetinib or encorafenib, BID, same dose level as in
the parent study.

Participants enrolled in this Continuation Sub-Study have been determined by
the investigators to have derived clinical benefit from study intervention.
More detailed information about the known and expected benefits and risks and
reasonably expected AEs of binimetinib or encorafenib may be found in the IB's,
which are the SRSD's for this study.