Clincosm LogoSign in Get a demo

Mirdametinib + BGB-3245 in Advanced Solid Tumors

Sponsor
SpringWorks Therapeutics, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05580770
Collaborator
(none)
136
Enrollment
6
Locations
4
Arms
52
Anticipated Duration (Months)
22.7
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
136 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
The study will be conducted in two sequential parts: Part 1 dose escalation (Phase 1) and Part 2 dose expansion (Phase 2a).The study will be conducted in two sequential parts: Part 1 dose escalation (Phase 1) and Part 2 dose expansion (Phase 2a).
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official 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
Anticipated Study Start Date :
Mar 1, 2023
Anticipated Primary Completion Date :
Oct 31, 2026
Anticipated Study Completion Date :
Jun 30, 2027

Arms and Interventions

Arm Intervention/Treatment
Experimental: Phase 1 Dose Escalation Cohorts Ranging in Dose

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

Drug: Mirdametinib
Mirdametinib administered orally
Other Names:
  • PD-0325901

    • Drug: BGB-3245
    BGB-3245 administered orally
    Experimental: Phase 2 Dose Expansion A

    Participants with cutaneous melanoma harboring NRAS mutations

    Drug: Mirdametinib
    Mirdametinib administered orally
    Other Names:
  • PD-0325901

    • Drug: BGB-3245
    BGB-3245 administered orally
    Experimental: Phase 2 Dose Expansion B

    Participants with NSCLC harboring KRAS mutations

    Drug: Mirdametinib
    Mirdametinib administered orally
    Other Names:
  • PD-0325901

    • Drug: BGB-3245
    BGB-3245 administered orally
    Experimental: Phase 2 Dose Expansion C

    Participants with NSCLC or cutaneous melanoma harboring BRAF Class II or Class III mutation or BRAF Fusion mutation

    Drug: Mirdametinib
    Mirdametinib administered orally
    Other Names:
  • PD-0325901

    • Drug: BGB-3245
    BGB-3245 administered orally

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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.

    3. 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.

    4. 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

    1. 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

    2. 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.

    3. 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).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 SpringWorks clinical trial site La Jolla California United States 92093
    2 SpringWorks clinical trial site Orlando Florida United States 32806
    3 Massachusetts General Hospital Boston Massachusetts United States 02114
    4 SpringWorks clinical trial site Cleveland Ohio United States 44106
    5 Texas Oncology-Baylor Charles A. Sammons Cancer Center Dallas Texas United States 75246
    6 SpringWorks clinical trial site Melbourne Victoria Australia 3000

    Sponsors and Collaborators

    • SpringWorks Therapeutics, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    SpringWorks Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT05580770
    Other Study ID Numbers:
    • MEKRAF-AST-101
    First Posted:
    Oct 14, 2022
    Last Update Posted:
    Jan 27, 2023
    Last Verified:
    Jan 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Neoplasms

    Study Results

    No Results Posted as of Jan 27, 2023