Mirdametinib + BGB-3245 in Advanced Solid Tumors

NCT05580770 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: MEKRAF-AST-101
• Study Type: interventional
• Target: 23
• Locations: 2 countries
• Sites: 8

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.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (4)

• Incidence of Treatment Emergent Adverse Events

  Safety and tolerability endpoint evaluation via incidence of treatment emergent Adverse Events (TEAEs). TEAE severities were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0. AEs were coded using MedDRA Version 27.1.

  All adverse events were collected from the time of signing ICF until 30 days after the last dose of study treatment (an average of 3.48 months and up to 16.76 months).

• Maximum Tolerated Dose (Part 1 Only)

  The maximum tolerated dose (MTD) for mirdametinib and BGB-3245 administered as a combination, if any, will be based on safety and tolerability during the first 28 days of treatment in Cycle 1.

  Up to 18 months

• Recommended Phase 2 Dose [RP2D] (Part 1 Only)

  The recommended phase 2 dose (RP2D) for mirdametinib and BGB-3245 administered as a combination will be determined based on safety, tolerability, PK, preliminary anti-tumor efficacy, and other available data.

  Up to 24 months

• Objective Response Rate (Part 2 Only)

  Preliminary anti-tumor efficacy for the RP2D of mirdametinib and BGB-3245 administered as a combination as assessed by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI). Objective Response Rate (ORR) defined as the proportion of participants with complete response (CR) + partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

  Up to 24 months

Secondary Outcomes (3)

• Objective Response Rate (Part 1 Only)

  From participants' date of first dose of study treatment through end of treatment, an average of 3.5 months

• Duration of Response Rate

  Up to 36 months

• Change in Plasma Concentrations of Mirdametinib and BGB-3245

  Up to 24 months

Study Arms (5)

Phase 1 Dose Escalation, Cohort 1

EXPERIMENTAL

Participants with an oncogenic mutation or other genomic aberration of the MAPK pathway

Drug: Mirdametinib 2mg; Drug: BGB-3245 5mg

Phase 1 Dose Escalation, Cohort 2

EXPERIMENTAL

Participants with an oncogenic mutation or other genomic aberration of the MAPK pathway

Drug: Mirdametinib 2mg; Drug: BGB-3245 10mg

Phase 1 Dose Escalation, Cohort 3

EXPERIMENTAL

Participants with an oncogenic mutation or other genomic aberration of the MAPK pathway

Drug: Mirdametinib 2mg; Drug: BGB-3245 20mg

Phase 1 Dose Escalation, Cohort 4

EXPERIMENTAL

Participants with an oncogenic mutation or other genomic aberration of the MAPK pathway

Drug: Mirdametinib 3mg; Drug: BGB-3245 10mg

Phase 1 Dose Escalation, Cohort 5

EXPERIMENTAL

Participants with an oncogenic mutation or other genomic aberration of the MAPK pathway

Drug: Mirdametinib 4mg; Drug: BGB-3245 10mg

Interventions

Mirdametinib 2mg DRUG

Mirdametinib 2mg administered orally

Also known as: PD-0325901

Phase 1 Dose Escalation, Cohort 1; Phase 1 Dose Escalation, Cohort 2; Phase 1 Dose Escalation, Cohort 3

BGB-3245 5mg DRUG

BGB-3245 5mg administered orally

Also known as: Brimarafenib

Phase 1 Dose Escalation, Cohort 1

Mirdametinib 3mg DRUG

Mirdametinib 3mg administered orally

Also known as: PD-0325901

Phase 1 Dose Escalation, Cohort 4

Mirdametinib 4mg DRUG

Mirdametinib 4mg administered orally

Also known as: PD-0325901

Phase 1 Dose Escalation, Cohort 5

BGB-3245 10mg DRUG

BGB-3245 10mg administered orally

Also known as: Brimarafenib

Phase 1 Dose Escalation, Cohort 2; Phase 1 Dose Escalation, Cohort 4; Phase 1 Dose Escalation, Cohort 5

BGB-3245 20mg DRUG

BGB-3245 20mg administered orally

Also known as: Brimarafenib

Phase 1 Dose Escalation, Cohort 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• SpringWorks Therapeutics, Inc.: lead

Study Sites (8)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Yale-New Haven Hospital-Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Texas Oncology-Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Calvary Mater Newcastle

Waratah, 2298, Australia

Location

MeSH Terms

Interventions

mirdametinib

Results Point of Contact

• Title: Head of Clinical Operations
• Organization: SpringWorks Therapeutics

clinical@springworkstx.com

8772794870

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will be conducted in two sequential parts: Part 1 dose escalation (Phase 1) and Part 2 dose expansion (Phase 2a).

Study Record Dates

• First Submitted: September 22, 2022
• First Posted: October 14, 2022
• Study Start: February 3, 2023
• Primary Completion: January 15, 2025
• Study Completion: January 15, 2025
• Last Updated: May 1, 2026
• Results First Posted: May 1, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); US (6)