Mirdametinib + BGB-3245 in Advanced Solid Tumors

Phase 1

Terminated

• Conditions: Advanced Solid Tumor
• Interventions: Drug: Mirdametinib; Drug: BGB-3245

• Registration Number: NCT05580770
• Lead Sponsor: SpringWorks Therapeutics, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-09-22
• Study First Submitted QC: 2022-10-11
• Study First Posted: 2022-10-14
• Study Start: 2023-02-03
• Primary Completion: 2025-01-15
• Study Completion: 2025-01-15
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-13
• Last Update Posted: 2025-02-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

• 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

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

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 2 Dose Expansion A	BGB-3245	Participants with cutaneous melanoma harboring NRAS mutations
Phase 1 Dose Escalation Cohorts Ranging in Dose	Mirdametinib	Participants with an oncogenic mutation or other genomic aberration of the MAPK pathway
Phase 1 Dose Escalation Cohorts Ranging in Dose	BGB-3245	Participants with an oncogenic mutation or other genomic aberration of the MAPK pathway
Phase 2 Dose Expansion A	Mirdametinib	Participants with cutaneous melanoma harboring NRAS mutations
Phase 2 Dose Expansion B	Mirdametinib	Participants with NSCLC harboring KRAS mutations
Phase 2 Dose Expansion B	BGB-3245	Participants with NSCLC harboring KRAS mutations
Phase 2 Dose Expansion C	Mirdametinib	Participants with NSCLC or cutaneous melanoma harboring BRAF Class II or Class III mutation or BRAF Fusion mutation
Phase 2 Dose Expansion C	BGB-3245	Participants with NSCLC or cutaneous melanoma harboring BRAF Class II or Class III mutation or BRAF Fusion mutation

Primary Outcome Measures

Name	Time	Method
Incidence of treatment emergent adverse events	Up to 24 months	Safety and tolerability endpoint evaluation via incidence of treatment emergent Adverse Events (TEAEs).; TEAEs severities will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Maximum Tolerated Dose (Part 1 Only)	Up to 18 months	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.
Recommended Phase 2 Dose (Part 1 Only)	Up to 24 months	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.
Objective Response Rate (Part 2 Only)	Up to 24 months	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).

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (Part 1 Only)	Up to 24 months	Preliminary anti-tumor efficacy for the RP2D of mirdametinib and BGB-3245 administered as a combination as assessed by CT or MRI. ORR defined as the proportion of participants with CR + PR using RECIST v1.1
Duration of Response Rate	Up to 36 months	Duration of response rate in participants treated with the combination of mirdametinib and BGB-3245, defined as the time from response (CR + PR using RECIST v1.1) to disease progression and/or death.
Change in plasma concentrations of mirdametinib and BGB-3245	Up to 24 months	To determine the PK of mirdametinib and BGB-3245 administered as a combination in the eligible participant population. Plasma concentrations of mirdametinib and BGB-3245 will be measured to evaluate systemic exposures (AUC, Cmax, Ctrough, and other PK parameters as data allow).

Trial Locations

Locations (8)

UC San Diego Moores Cancer Center; 🇺🇸 La Jolla, California, United States

Yale-New Haven Hospital-Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

University Hospitals Cleveland Medical Center; 🇺🇸 Cleveland, Ohio, United States

Hospital of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Texas Oncology-Baylor Charles A. Sammons Cancer Center; 🇺🇸 Dallas, Texas, United States

Peter MacCallum Cancer Centre; 🇦🇺 Melbourne, Victoria, Australia

Calvary Mater Newcastle; 🇦🇺 Waratah, Australia