Trial Title:
A Study to Assess the Efficacy and Safety of FORE8394 in Participants with Cancer Harboring BRAF Alterations
NCT ID:
NCT05503797
Condition:
Cancer Harboring BRAF Alterations
Conditions: Official terms:
Cobicistat
Conditions: Keywords:
BRAF alterations
BRAF Fusions
BRAF V600E
BRAF Class 1
BRAF Class 2
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
All four open-label subprotocols will enroll patients independently of one another, in
parallel. Subprotocol D is a 2-arm, randomized study. The other subprotocols are
single-arm.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Plixorafenib
Description:
Oral tablets
Arm group label:
Subprotocol A
Arm group label:
Subprotocol B
Arm group label:
Subprotocol C
Arm group label:
Subprotocol D
Other name:
FORE8394
Other name:
PLX8394
Intervention type:
Drug
Intervention name:
Cobicistat
Description:
Oral tablets
Arm group label:
Subprotocol B
Arm group label:
Subprotocol C
Arm group label:
Subprotocol D
Other name:
TYBOST(R)
Summary:
The objective of this study is to evaluate the efficacy of plixorafenib in participants
with locally advanced or metastatic solid tumors, or recurrent or progressive primary
central nervous system (CNS) tumors harboring BRAF fusions, or in participants with rare
solid tumors, melanoma, thyroid, or recurrent primary CNS tumors harboring BRAF V600E
mutation. This will be conducted as four open-label subprotocols (F8394-201A; F8394-201B;
F8394-201C; F8394-201D) under one master protocol.
Criteria for eligibility:
Criteria:
Inclusion Criteria
Subprotocol A:
1. Male and female, ≥10 years of age, and weighing ≥30 kg.
2. Histologic diagnosis of a solid tumor or primary CNS tumor.
3. Documentation of BRAF gene fusion in tumor and/or blood detected by an analytically
validated test by DNA sequencing or RNA (transcriptome) sequencing at CLIA or
CLIA-equivalent laboratory or sponsor-designated central laboratory.
4. Have an archival tissue sample available meeting protocol requirements. If an
archival tissue sample is not available, a newly obtained (before treatment) tumor
biopsy may be submitted instead.
5. Consent to provide scan(s) prior to baseline to assess change in tumor trajectory.
6. Received all available standard therapy, is intolerant to available therapies, or
the investigator has determined that treatment with standard therapy is not
appropriate.
7. All adverse events related to prior therapies (chemotherapy; radiotherapy; surgery)
must have resolved to Grade 1 or baseline except for
1. Alopecia (Grade ≤2)
2. Sensory neuropathy (Grade ≤2)
3. Other adverse events that have resolved to Grade ≤2 that, according to the
clinical judgment of the investigator, do not constitute a safety risk to the
participant.
Subprotocol B:
1. Male and female, ≥10 years of age, and weighing ≥30 kg.
2. Histological diagnosis of a primary CNS tumor, including but not limited to the
following:
1. Adults (≥18 years) with Grade 1-4 glioma or glioneuronal tumor (including
glioblastoma, anaplastic astrocytoma, high grade astrocytoma with piloid
features, pilocytic astrocytoma, gliosarcoma, anaplastic pleomorphic
xanthoastrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma,
not otherwise specified [NOS], ganglioglioma, or recurrent LGG). OR
2. Pediatric patients (10-17 years of age) with a Grade 3 or 4 glioma or
glioneuronal tumor, including those with a prior, histologically confirmed,
diagnosis of a low-grade glioma or glioneuronal tumor and now have radiographic
or histopathological findings consistent with WHO [2021] Grade 3 or 4 primary
CNS tumor.
3. Participants must have unresectable, locally advanced or metastatic disease
that:
i. Had prior treatment with radiotherapy and/or first-line chemotherapy or
concurrent chemoradiation therapy OR
- Note: Participants who have a WHO Grade 3 or 4 glioma for whom chemotherapy
and/or radiotherapy is not considered standard of care may remain eligible for
the study. Consult the Medical Lead to discuss and determine if participant is
eligible for enrollment.
ii. Is intolerant to available therapies OR iii. The investigator has determined
that treatment with standard therapy is not appropriate.
3. Documented BRAF V600E mutation in tumor and/or blood detected by an analytically
validated test at CLIA or CLIA-equivalent laboratory approved by sponsor or
sponsor-designated central test.
4. An archival tissue sample available meeting protocol requirements, or fresh biopsy
is required if the archival sample is not available for retrospective confirmation
test. Tissue obtained most proximal to initiating this subprotocol is preferred.
5. Measurable disease based upon specified response criteria, as determined by the
radiographic BICR.
6. All adverse events related to prior therapies (eg, chemotherapy, radiotherapy,
surgery) must have resolved to Grade 1 or baseline except for:
1. Alopecia (Grade ≤2)
2. Sensory neuropathy (Grade ≤2)
3. Other adverse events that have resolved to Grade ≤2 that, according to the
clinical judgment of the investigator, do not constitute a safety risk to the
participant
7. Participants who are receiving corticosteroid treatment must be on a stable or
decreasing dose of ≤8 mg/day of dexamethasone or equivalent corticosteroid treatment
for 7 days prior to first dose of study treatments.
Subprotocol C:
1. Male and female, ≥10 years of age, and weighing ≥30 kg.
2. Histologic diagnosis of a rare BRAF V600E-mutated solid tumor that is unresectable,
locally advanced or metastatic.
3. Documented BRAF V600E mutation in tumor and/or blood detected by an analytically
validated test at CLIA or CLIA-equivalent laboratory approved by sponsor or
sponsor-designated central test.
4. Have an archival tissue sample available meeting protocol requirements. If an
archival tissue sample is not available, a newly obtained (before treatment) tumor
biopsy may be submitted instead.
5. Consent to provide scan(s) prior to baseline to assess change in tumor trajectory.
6. Received all available standard therapy, is intolerant to available therapies, or
the investigator has determined that treatment with standard therapy is not
appropriate.
7. All adverse events related to prior therapies (chemotherapy; radiotherapy; surgery)
must have resolved to Grade 1 or baseline except for
1. Alopecia (Grade ≤2)
2. Sensory neuropathy (Grade ≤2)
3. Other adverse events that have resolved to Grade ≤2 that, according to the
clinical judgment of the investigator, do not constitute a safety risk to the
participant.
Subprotocol D:
1. Male and female, ≥10 years of age, and weighing ≥30 kg.
2. Histologic diagnosis of a metastatic melanoma or thyroid cancer harboring a BRAF
V600E mutation.
3. Consent to provide a tumor biopsy.
4. All adverse events related to prior therapies (chemotherapy; radiotherapy; surgery)
must have resolved to Grade 1 or baseline except for
1. Alopecia (Grade ≤2)
2. Sensory neuropathy (Grade ≤2)
3. Other adverse events that have resolved to Grade ≤2 that, according to the
clinical judgment of the investigator, do not constitute a safety risk to the
participant.
Exclusion Criteria:
Subprotocol A:
1. Participants with known co-occurring NF1 alteration and/or RAS-related mutations.
2. Participants with evidence of subclonal mutations or heterogeneity that are
indicative of a prior treatment effect instead of a driver mutation.
3. Prior treatment with MAPK inhibitors active for Class 2 BRAF alterations for
advanced unresectable or metastatic disease (including but not limited to
tovorafenib [formerly known as DAY 101, TAK 580, and MLN 2480], KIN-2787, BGB-3245,
and CFT1946).
- Note: Participants with pediatric-type LGGs (molecular classification by
WHO2021; diagnosed at ≤25 years of age) who had received prior treatment(s)
with RAF/BRAF inhibitors are eligible for enrollment, provided there was no
evidence of tumor progression on that therapy or within 4 weeks of
discontinuation, based upon radiographic assessment.
4. Tyrosine kinase inhibitor(s) and/or targeted therapies are allowed (other than
BRAF/MAPK pathway inhibitors per Exclusion Criteria 3 and 4) and will be restricted
to no more than the number of lines of therapy that are consistent with standard
treatment guidelines. NOTE: There is no restriction on the number of lines of
chemotherapy or immunotherapy.
5. Malignancy with co-occurring activating RAS mutation(s) at any time.
6. Uncontrolled intercurrent illness that would limit compliance with study
requirements.
7. Current or planned participation in a study of an investigational agent or device.
8. Have impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of oral plixorafenib or cobicistat (such as
ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption
syndrome, and small bowel resection).
9. Are currently receiving (within 7 days of Cycle 1 Day 1) or are planning to receive
during participation:
1. Agents that are known strong inducers or inhibitors of CYP3A4 . Restrictions
include foods or herbal medications, including grapefruit juice,
grapefruit/grapefruit related citrus fruits (eg, Seville oranges, pomelos), and
St. John's Wort.
Subprotocol B:
1. Prior treatment with BRAF, ERK, and/or MEK inhibitor(s).
2. Known or suspected neurofibromatosis-1 (NF-1) and/or Ras related gene alterations.
3. Uncontrolled intercurrent illness that would limit compliance with study
requirements.
4. Active infection requiring systemic therapy.
5. Current or planned participation in a study of an investigational agent or device.
6. Have impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of oral plixorafenib or cobicistat (such as
ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption
syndrome, small bowel resection).
7. Grade ≥ 2 changes in AST, ALT, gamma-glutamyl transaminase (GGT), or bilirubin
attributed to prior immune checkpoint inhibitor treatment are exclusionary, even if
resolved.
8. Are currently receiving (within 7 days of Cycle 1 Day 1) or are planning to receive
during participation:
1. Agents that are known strong inducers or inhibitors of CYP3A4 (other than
cobicistat). Restrictions include foods or herbal medications, including
grapefruit juice, grapefruit/grapefruit related citrus fruits (eg, Seville
oranges, pomelos), and St. John's Wort.
2. Agents that are contraindicated with cobicistat Note: For participants with no
other option except agents with potential drug interactions with cobicistat,
but which are not contraindicated, the dose of that agent must be altered or
the regimen must follow the cobicistat prescribing information and be approved
by the medical monitor.
Subprotocol C:
1. Diagnosis of colorectal adenocarcinoma or pancreatic ductal adenocarcinoma
(neuroendocrine or acinar tumors are eligible).
2. Participant has CNS metastases. If participants have symptoms that could be
indicative of CNS metastases or tumors that are at high risk of CNS metastases, CNS
imaging is required prior to the first dose of plixorafenib (MRI with contrast
preferred).
3. Prior treatment with BRAF, ERK, and/or MEK inhibitor(s).
4. Known or suspected neurofibromatosis-1 (NF-1) and/or RAS related gene alterations.
5. Uncontrolled intercurrent illness that would limit compliance with study
requirements.
6. Active infection requiring systemic therapy.
7. Current or planned participation in a study of an investigational agent or device.
8. Have impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of oral plixorafenib or cobicistat (such as
ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption
syndrome, small bowel resection).
9. Grade ≥ 2 changes in AST, ALT, gamma-glutamyl transaminase (GGT), or bilirubin
attributed to prior immune checkpoint inhibitor treatment are exclusionary, even if
resolved.
10. Are currently receiving (within 7 days of Cycle 1 Day 1) or are planning to receive
during participation:
1. Agents that are known strong inducers or inhibitors of CYP3A4 (other than
cobicistat). Restrictions include foods or herbal medications, including
grapefruit juice, grapefruit/grapefruit related citrus fruits (eg, Seville
oranges, pomelos), and St. John's Wort.
2. Agents that are contraindicated with cobicistat Note: For participants with no
other option except agents with potential drug interactions with cobicistat,
but which are not contraindicated, the dose of that agent must be altered or
the regimen must follow the cobicistat prescribing information and be approved
by the medical monitor.
Subprotocol D:
1. Known or suspected neurofibromatosis-1 (NF-1) and/or RAS related gene alterations.
2. Participant has CNS metastases.
3. Uncontrolled intercurrent illness that would limit compliance with study
requirements.
4. Active infection requiring systemic therapy.
5. Current or planned participation in a study of an investigational agent or device.
6. Have impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of oral plixorafenib or cobicistat (such as
ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption
syndrome, small bowel resection).
7. Grade ≥ 2 changes in AST, ALT, gamma-glutamyl transaminase (GGT), or bilirubin
attributed to prior immune checkpoint inhibitor treatment are exclusionary, even if
resolved.
8. Are currently receiving (within 7 days of Cycle 1 Day 1) or are planning to receive
during participation:
1. Agents that are known strong inducers or inhibitors of CYP3A4 (other than
cobicistat). Restrictions include foods or herbal medications, including
grapefruit juice, grapefruit/grapefruit related citrus fruits (eg, Seville
oranges, pomelos), and St. John's Wort.
2. Agents that are contraindicated with cobicistat Note: For participants with no
other option except agents with potential drug interactions with cobicistat,
but which are not contraindicated, the dose of that agent must be altered or
the regimen must follow the cobicistat prescribing information and be approved
by the medical monitor.
Gender:
All
Minimum age:
10 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
UCSF Helen Diller Family Comprehensive Cancer Center
Address:
City:
San Francisco
Zip:
94143
Country:
United States
Status:
Recruiting
Contact:
Last name:
Nicholas Butowski
Facility:
Name:
University of California Los Angeles Rheumatology
Address:
City:
Westwood
Zip:
90095-6984
Country:
United States
Status:
Recruiting
Contact:
Last name:
Noah Federman
Facility:
Name:
University of Miami Hospital and Clinics
Address:
City:
Miami
Zip:
33136
Country:
United States
Status:
Recruiting
Contact:
Last name:
Macarena De la Fuente
Facility:
Name:
The John Hopkins Hospital
Address:
City:
Baltimore
Zip:
21287
Country:
United States
Status:
Recruiting
Contact:
Last name:
Karisa Schreck
Facility:
Name:
Tufts Medical Center
Address:
City:
Boston
Zip:
02111
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jeyapalan Suriya
Facility:
Name:
St. Luke's Hospital
Address:
City:
Duluth
Zip:
55805
Country:
United States
Status:
Recruiting
Contact:
Last name:
Homam Alkaied
Facility:
Name:
Mosaic Life Care at Saint Joseph - Medical Center
Address:
City:
St Joseph
Zip:
64506
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rony Abou-Jawde
Facility:
Name:
Nebraska Cancer Specialists - Midwest Cancer Center - Legacy
Address:
City:
Omaha
Zip:
68130
Country:
United States
Status:
Recruiting
Contact:
Last name:
Joel Michalski
Facility:
Name:
Overlook Medical Center
Address:
City:
Summit
Zip:
07901
Country:
United States
Status:
Recruiting
Contact:
Last name:
Robert Aiken
Facility:
Name:
Columbia University Irving Medical Center
Address:
City:
New York
Zip:
10032
Country:
United States
Status:
Recruiting
Contact:
Last name:
Luca Szalontay
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Eric Sherman
Facility:
Name:
Nationwide Children's Hospital
Address:
City:
Colombus
Zip:
43205
Country:
United States
Status:
Recruiting
Contact:
Last name:
Mark Ranalli
Facility:
Name:
Toledo Clinic Cancer Center
Address:
City:
Toledo
Zip:
43623
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rex Mowat
Facility:
Name:
Lifespan Cancer Institute - Rhode Island Hospital
Address:
City:
Providence
Zip:
02903
Country:
United States
Status:
Recruiting
Contact:
Last name:
Samit Sarangi
Facility:
Name:
Baylor Scott & White Research Institute
Address:
City:
Dallas
Zip:
75246
Country:
United States
Status:
Recruiting
Contact:
Last name:
Karen Fink
Facility:
Name:
Baylor Scott & White Medical Center
Address:
City:
Temple
Zip:
43205
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jennifer Murillo
Facility:
Name:
University of Washington School of Medicine
Address:
City:
Seattle
Zip:
98109
Country:
United States
Status:
Recruiting
Contact:
Last name:
Vyshak Venur
Facility:
Name:
West Virginia University Health Sciences Campus
Address:
City:
Morgantown
Zip:
26506
Country:
United States
Status:
Recruiting
Contact:
Last name:
Sonikpreet Aulakh
Facility:
Name:
Sunny brook Health Sciences Centre- Bayview Campus
Address:
City:
Toronto
Zip:
M4N 3M5
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Mary Jane Lim-Fay
Facility:
Name:
Centre Hospitalier Universitaire Sainte-Justine
Address:
City:
Montréal
Zip:
H3T 1C5
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Sebastien Perreault
Facility:
Name:
Institut Bergonie
Address:
City:
Bordeaux Cedex
Zip:
33000
Country:
France
Status:
Recruiting
Contact:
Last name:
Antoine Italiano
Facility:
Name:
Hôpital Nord de Marseille
Address:
City:
Marseille
Zip:
13005
Country:
France
Status:
Recruiting
Contact:
Last name:
Pascale Tomasini
Facility:
Name:
Hôpital Morvan
Address:
City:
Brest
Zip:
29200
Country:
France
Status:
Recruiting
Contact:
Last name:
Jean-Philippe Metges
Facility:
Name:
Hôpital Universitaire Pitié Salpêtrière
Address:
City:
Paris
Zip:
75013
Country:
France
Status:
Recruiting
Contact:
Last name:
Mehdi Touat
Facility:
Name:
Institut de Cancerologie de l'Ouest- Angers
Address:
City:
Angers
Zip:
49055
Country:
France
Status:
Recruiting
Contact:
Last name:
Lila Autier
Facility:
Name:
Gustave Roussy
Address:
City:
Villejuif
Zip:
94805
Country:
France
Status:
Recruiting
Contact:
Last name:
Mihaela Diana Aldea
Facility:
Name:
Universitätsklinikum Heidelberg
Address:
City:
Heidelberg
Zip:
69120
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Antje Wick
Facility:
Name:
Krankenhaus Nordwest
Address:
City:
Frankfurt
Zip:
60488
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Thorsten Oliver Götze
Facility:
Name:
Charité - Universitätsmedizin Berlin
Address:
City:
Berlin
Zip:
13353
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Dominik Modest
Facility:
Name:
Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST
Address:
City:
Meldola
Zip:
47014
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Alberto Farolfi
Facility:
Name:
Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
Address:
City:
Napoli
Zip:
80131
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Paolo Ascierto
Facility:
Name:
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale San Raffaele
Address:
City:
Milan
Zip:
20132
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Andrea Necchi
Facility:
Name:
Catholic University of Korea Saint Vincent's Hospital
Address:
City:
Suwon-si
Zip:
16247
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Byoung Yong Shim
Facility:
Name:
Seoul National University Hospital
Address:
City:
Suwon
Zip:
443-721
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Hyun Woo Lee
Facility:
Name:
Dong-A University Hospital
Address:
City:
Busan
Zip:
602-812
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Sung Yong Oh
Facility:
Name:
Chonnam National University Hwasun Hospital
Address:
City:
Hwasun
Zip:
58128
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
In-Jae Oh
Facility:
Name:
Seoul National University Hospital
Address:
City:
Seoul
Zip:
03080
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Tae Min Kim
Facility:
Name:
Severance Hospital
Address:
City:
Seoul
Zip:
03722
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Sang Joon Shin
Facility:
Name:
Hospital Clinico Universitarlo de Santiago
Address:
City:
Santiago De Compostela
Zip:
15706
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Alexandra Cortegoso
Facility:
Name:
Hospital Clinico Universitarlo de Valencia
Address:
City:
València
Zip:
46010
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Valentina Gambardella
Facility:
Name:
Hospital Universitari Vall d'Hebron
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Maria Vieito Villar
Facility:
Name:
Hospital Infantil Universitario Niño Jesús
Address:
City:
Madrid
Zip:
28009
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Atienza Alvaor Lassaletta
Facility:
Name:
Hospital Universitario 12 de Octubre
Address:
City:
Madrid
Zip:
28041
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Guillermo De Velasco Oria de Rueda
Facility:
Name:
Hospital Universitario Virgen del Rocío
Address:
City:
Sevilla
Zip:
41013
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Alejandro Falcon Gonzalez
Facility:
Name:
Skånes Universitetssjukhus
Address:
City:
Lund
Zip:
221 85
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Ana Carneiro
Facility:
Name:
Karolinska Universitetssjukhuset
Address:
City:
Solna
Zip:
171 64
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Jeffrey Yachnin
Facility:
Name:
The Christie NHS Foundation Trust
Address:
City:
Manchester
Zip:
M20 4BX
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Colin Lindsay
Facility:
Name:
Sarah Cannon Research Institute
Address:
City:
London
Zip:
W1G 6AD
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Elisa Fontana
Start date:
February 21, 2023
Completion date:
August 28, 2026
Lead sponsor:
Agency:
Fore Biotherapeutics
Agency class:
Industry
Source:
Fore Biotherapeutics
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05503797