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Trial record 1 of 1 for:    MEKRAF-AST-101
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Mirdametinib + BGB-3245 in Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT05580770
Recruitment Status : Recruiting
First Posted : October 14, 2022
Last Update Posted : October 27, 2023
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: Mirdametinib Drug: BGB-3245 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated 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).
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
Actual Study Start Date : February 3, 2023
Estimated Primary Completion Date : October 31, 2026
Estimated Study Completion Date : June 30, 2027

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 Name: 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 Name: 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 Name: 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 Name: PD-0325901

Drug: BGB-3245
BGB-3245 administered orally




Primary Outcome Measures :
  1. Incidence of treatment emergent adverse events [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05580770


Contacts
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Contact: SpringWorks Clinical 877-279-4870 clinical@springworkstx.com

Locations
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United States, California
UC San Diego Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Contact: Katie O'Neil       croneil@health.ucsd.edu   
Principal Investigator: Gregory Daniels, MD         
United States, Connecticut
Yale-New Haven Hospital-Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06520
Contact: Leah Centanne    203-785-2134    leah.centanne@yale.edu   
Principal Investigator: Mario Sznol, MD         
United States, Florida
Orlando Health Cancer Institute Recruiting
Orlando, Florida, United States, 32806
Contact: Melinda Porter    321-841-7246    Janice.Porter@orlandohealth.com   
Principal Investigator: Sajeve S Thomas, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Ryan J Sullivan, MD    617-724-4000    RSULLIVAN7@PARTNERS.ORG   
Principal Investigator: Ryan J Sullivan, MD         
United States, Ohio
University Hospitals Cleveland Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Ankit Mangla, MD    216-844-3951    ankit.mangla@UHhospitals.org   
Principal Investigator: Ankit Mangla, MD         
United States, Pennsylvania
Hospital of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Jennifer Louie    215-220-9668    Jennifer.Louie2@pennmedicine.upenn.edu   
Principal Investigator: Ravi Amaravadi, MD         
United States, Texas
Texas Oncology-Baylor Charles A. Sammons Cancer Center Recruiting
Dallas, Texas, United States, 75246
Contact: Christine Terraciano    214-370-1942    Christine.Terraciano@usoncology.com   
Principal Investigator: Charles L Cowey, MD         
Australia, Victoria
Peter MacCallum Cancer Centre Recruiting
Melbourne, Victoria, Australia, 3000
Contact       pcctu.edd@petermac.org   
Principal Investigator: Jayesh Desai, MD         
Australia
Calvary Mater Newcastle Recruiting
Waratah, Australia, 2298
Contact: Fiona Day, MD    02 4014 3575    Fiona.Day@calvarymater.org.au   
Principal Investigator: Fiona Day, MD         
Sponsors and Collaborators
SpringWorks Therapeutics, Inc.
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Responsible Party: SpringWorks Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05580770    
Other Study ID Numbers: MEKRAF-AST-101
First Posted: October 14, 2022    Key Record Dates
Last Update Posted: October 27, 2023
Last Verified: October 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms