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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05580770




Registration number
NCT05580770
Ethics application status
Date submitted
22/09/2022
Date registered
14/10/2022
Date last updated
9/04/2024

Titles & IDs
Public title
Mirdametinib + BGB-3245 in Advanced Solid Tumors
Scientific title
A Phase 1/2a Open-Label, Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of Mirdametinib in Combination With BGB-3245 in Patients With Advanced Solid Tumors
Secondary ID [1] 0 0
MEKRAF-AST-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumor 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Mirdametinib
Treatment: Drugs - BGB-3245

Experimental: Phase 1 Dose Escalation Cohorts Ranging in Dose - Participants with an oncogenic mutation or other genomic aberration of the MAPK pathway

Experimental: Phase 2 Dose Expansion A - Participants with cutaneous melanoma harboring NRAS mutations

Experimental: Phase 2 Dose Expansion B - Participants with NSCLC harboring KRAS mutations

Experimental: Phase 2 Dose Expansion C - Participants with NSCLC or cutaneous melanoma harboring BRAF Class II or Class III mutation or BRAF Fusion mutation


Treatment: Drugs: Mirdametinib
Mirdametinib administered orally

Treatment: Drugs: BGB-3245
BGB-3245 administered orally
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of treatment emergent adverse events
Timepoint [1] 0 0
Up to 24 months
Primary outcome [2] 0 0
Maximum Tolerated Dose (Part 1 Only)
Timepoint [2] 0 0
Up to 18 months
Primary outcome [3] 0 0
Recommended Phase 2 Dose (Part 1 Only)
Timepoint [3] 0 0
Up to 24 months
Primary outcome [4] 0 0
Objective Response Rate (Part 2 Only)
Timepoint [4] 0 0
Up to 24 months
Secondary outcome [1] 0 0
Objective Response Rate (Part 1 Only)
Timepoint [1] 0 0
Up to 24 months
Secondary outcome [2] 0 0
Duration of Response Rate
Timepoint [2] 0 0
Up to 36 months
Secondary outcome [3] 0 0
Change in plasma concentrations of mirdametinib and BGB-3245
Timepoint [3] 0 0
Up to 24 months

Eligibility
Key inclusion criteria
Key

- Able to provide informed consent

- At least 18 years of age on day of signing ICF

- Advanced, metastatic or unresectable solid cancer that has not responded to or
progressed during or after at least 1 line of appropriate therapy or for which there
is no treatment available or prior therapy was not tolerated.

- Part 1: oncogenic mutation or other genomic aberration of the MAPK pathway

- Part 2: oncogenic mutation or genomic aberration defined below:

- Cohort A: cutaneous melanoma harboring NRAS mutations.

- Cohort B: non-small cell lung cancer (NSCLC) harboring a KRAS mutation.

- Cohort C: NSCLC or cutaneous melanoma harboring BRAF Class II or Class III
mutations or BRAF Fusion mutation.

- Must have archival tumor tissue or agree to a fresh tumor biopsy at screening

- Measurable disease per RECIST 1.1

- Eastern Cooperative Oncology Group (ECOG) performance status of = 2

- Adequate organ function and no transfusion within 14 days of first dose

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Central Nervous System metastases, leptomeningeal carcinomatosis or untreated spinal
cord compression

- History of glaucoma

- Active parathyroid disorder or history of malignancy associated hypercalcemia

- Clinically significant cardiac disease within the past 6 months of signing ICF

- History of toxicity from another RAF, MEK, ERK inhibitor requiring discontinuation of
treatment from these agents

- Severe or uncontrolled systemic disease

- Inability to swallow oral medications

- Clinically significant active infection (HIV, Hepatitis B or Hepatitis C)

- History of or ongoing Immune Thrombocytopenia (ITP), Von Willebrand disease and/or
other past or present bleeding disorders

- Underlying medical conditions in investigator's opinion to be unfavorable to be a part
of the study

- Major surgical procedure or significant traumatic injury within 4 weeks prior to first
dose or anticipates need for major surgery while on study

- Systemic anti-cancer therapy within 2 weeks or 5 half-lives before first dose

- Concomitant systemic or glucocorticoid therapy within 2 weeks before first dose

- Concomitant medicines that are strong CYP3A4 inhibitors or inducers within 2 weeks or
5 half-lives before first dose

- Live vaccine within 4 weeks before first dose

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/02/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/06/2027
Actual
Sample size
Target
136
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 0 0
Calvary Mater Newcastle - Waratah
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment postcode(s) [2] 0 0
2298 - Waratah
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
SpringWorks Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
A Phase 1/2a open-label, multicenter, dose escalation and expansion study of mirdametinib in
combination with BGB-3245 in adult participants with histologically confirmed, advanced
(American Joint Committee on Cancer (AJCC) Stage III or IV) metastatic or unresectable solid
cancer that is refractory to or has progressed during or after at least 1 line of appropriate
prior systemic anti-cancer therapy including chemotherapy, immunotherapy, or appropriate
targeted therapy, or for which there is no treatment available, or prior standard of care
therapy was not tolerated.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05580770
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
SpringWorks Clinical
Address 0 0
Country 0 0
Phone 0 0
877-279-4870
Fax 0 0
Email 0 0
clinical@springworkstx.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05580770