Trial Title:
A Study of BDTX-4933 in Patients With KRAS, BRAF and Select RAS/MAPK Mutation-Positive Cancers
NCT ID:
NCT05786924
Condition:
Non-small Cell Lung Cancer
Histiocytic Neoplasm
Histiocytosis
Melanoma
Melanoma (Skin)
BRAF Gene Mutation
BRAF V600E
BRAF V600 Mutation
BRAF Mutation-Related Tumors
BRAF
Metastatic Lung Non-Small Cell Carcinoma
Metastatic Melanoma
Metastatic Lung Cancer
Recurrent Melanoma
Recurrent Lung Cancer
Recurrent Lung Non-Small Cell Carcinoma
NSCLC
Solid Tumor
Solid Carcinoma
KRAS G12D
KRAS G12V
KRAS Mutation-Related Tumors
NRAS Gene Mutation
Thyroid Cancer
Thyroid Carcinoma
Colorectal Cancer
Colorectal Carcinoma
Recurrent Histiocytic and Dendritic Cell Neoplasm
Brain Metastases
Recurrent NSCLC
KRAS G13C
Acquired Resistance to KRAS G12C Inhibitor
KRAS G12A
KRAS G12F
KRAS G12R
KRAS G13D
Conditions: Official terms:
Carcinoma
Neoplasms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Melanoma
Brain Neoplasms
Thyroid Neoplasms
Histiocytosis
Thyroid Diseases
Recurrence
Conditions: Keywords:
BRAF Class I
BRAF Class II
BRAF Class III
KRAS
Intolerant histiocytic neoplasm
BDTX-4933
Phase 1
dose escalation
dose expansion
MAPK
mitogen-activated protein kinase
RAS
RAF
Upstream oncogenic alterations
RAF inhibitor
intracranial disease
CRAF
NRAS
RAF fusions
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Active, not recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
BDTX-4933
Description:
RAF inhibitor targeting all classes of oncogenic BRAF alterations (Classes I, II, and
III) and constitutively active CRAF, KRAS or NRAS mutations
Arm group label:
Phase 1 Dose Escalation
Arm group label:
Phase 1 Dose Expansion
Summary:
BDTX-4933-101 is a first-in-human, open-label, Phase 1 dose escalation and an expansion
cohort study designed to evaluate the safety and tolerability, maximum tolerated dose
(MTD) and the preliminary recommended Phase 2 dose (RP2D), and antitumor activity of
BDTX-4933. The study population for the Dose Escalation part of the study comprises
adults with recurrent advanced/metastatic non-small cell lung cancer (NSCLC) harboring
KRAS non-G12C mutations, BRAF, or CRAF (RAF1) mutations, advanced/metastatic melanoma
harboring BRAF or NRAS mutations, histiocytic neoplasms harboring BRAF, CRAF, or NRAS
mutations, and other solid tumors harboring BRAF mutations. The study population for the
Dose Expansion part of the study comprises adults with recurrent advanced/metastatic
NSCLC harboring KRAS non-G12C mutations. All patients will self-administer BDTX-4933
orally in 28-day cycles until disease progression, toxicity, withdrawal of consent, or
termination of the study.
Criteria for eligibility:
Criteria:
Key Inclusion Criteria:
1. Disease criteria:
1. Histologically or cytologically confirmed recurrent/advanced (unresectable) or
metastatic solid tumors or histiocytic neoplasms with documented RAS or BRAF
mutations.
Note: Patients may have stable central nervous system (CNS) metastases.
Patients with active CNS metastases or primary CNS tumors associated with
progressive neurological symptoms or needing increased doses of corticosteroids
to control the CNS disease are excluded from the study.
2. Dose Escalation cohorts:
- NSCLC with KRAS non-G12C mutations, including other mutations at KRAS-G12
(eg, G12V/G12D) and other oncogenic variants of KRAS mutations on G13 and
Q61 amino acid residues, BRAF, or CRAF mutations.
- Melanoma with BRAF, CRAF, or NRAS mutations.
- Histiocytic neoplasms with BRAF or NRAS mutations.
- Thyroid carcinoma with BRAF mutations.
- Colorectal carcinoma with BRAF (Class II or III) mutations with Sponsor
approval.
- Other solid tumors with BRAF Class I mutations after prior treatment with
a BRAF/MEK inhibitor or local standard-of-care with Sponsor approval.
3. Dose Expansion cohort:
Recurrent advanced/metastatic NSCLC with KRAS non-G12C mutations without small cell
lung cancer transformation with progressive disease confirmed by radiographic
assessment.
2. Prior standard-of-care
For dose levels <200 mg once daily and/or not at preliminary RP2D(s):
1. Exhausted all available standard-of-care therapies or, in the opinion of the
Investigator, would be unlikely to tolerate or derive clinically meaningful
benefit from available standard-of-care therapy.
2. Patients with eligible tumors harboring BRAF V600E mutations must have received
FDA approved BRAF targeted therapy, BRAF/MEK inhibitors combination, or BRAF
inhibitors combination.
For dose levels ≥200 mg once daily or at preliminary RP2D(s):
a. Patients must have received at least 1 but no more than 2 prior lines of systemic
therapy for metastatic/advanced disease (adjuvant and maintenance therapy do not
count towards the limit).
3. Evaluable or measurable disease in dose escalation and measurable disease only for
dose expansion cohorts.
4. Adequate bone marrow and organ function.
5. Recovered from toxicity to prior anti-cancer therapy.
6. Appropriate candidate for BDTX-4933 monotherapy.
7. Life expectancy of >=12 weeks in the opinion of the Investigator.
Key Exclusion Criteria:
1. Cancer that has a known MEK1/2 mutation.
2. Major surgery within 4 weeks of study entry or planned during study.
3. Ongoing anticancer therapy.
4. Ongoing radiation therapy.
5. Uncontrolled or active clinically relevant bacterial, fungal, or specific viral
infection requiring systemic therapy.
6. Symptomatic spinal cord compression.
7. Evidence of active malignancy (other than study-specific malignancies) requiring
systemic therapy within the next 2 years.
8. History or current evidence of retinal vein occlusion (RVO) or current risk factors
for RVO.
9. Females who are pregnant or breastfeeding.
10. Actively receiving systemic treatment or direct medical intervention on another
therapeutic clinical study.
11. Prior use of experimental agents that target the KRAS/BRAF/MEK/ERK pathway.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Banner Health- MD Anderson Cancer Center
Address:
City:
Gilbert
Zip:
85234
Country:
United States
Facility:
Name:
Cedars Sinai Medical Center
Address:
City:
Los Angeles
Zip:
90048
Country:
United States
Facility:
Name:
University of Colorado - Aurora Cancer Center
Address:
City:
Aurora
Zip:
80045
Country:
United States
Facility:
Name:
Georgetown University Lombardi Cancer Center
Address:
City:
Washington
Zip:
20007
Country:
United States
Facility:
Name:
Moffitt Cancer Center
Address:
City:
Tampa
Zip:
33612
Country:
United States
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Facility:
Name:
South Texas Accelerated Research Therapeutics (START) Midwest
Address:
City:
Grand Rapids
Zip:
49546
Country:
United States
Facility:
Name:
Masonic Cancer Center University of Minnesota
Address:
City:
Minneapolis
Zip:
55455
Country:
United States
Facility:
Name:
Washington University
Address:
City:
Saint Louis
Zip:
63130
Country:
United States
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Facility:
Name:
UNC Hospitals, The University of North Carolina at Chapel Hill
Address:
City:
Chapel Hill
Zip:
27514
Country:
United States
Facility:
Name:
Huntsman Cancer Institute (University of Utah)
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Facility:
Name:
NEXT Virginia
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Facility:
Name:
Fred Hutchinson Cancer Research Center
Address:
City:
Seattle
Zip:
98109
Country:
United States
Start date:
April 18, 2023
Completion date:
December 2026
Lead sponsor:
Agency:
Black Diamond Therapeutics, Inc.
Agency class:
Industry
Source:
Black Diamond Therapeutics, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05786924
