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No longer recruiting (closed or complete)Last updated: 18 November 2024

This study seeks to determine the appropriate dose level and effectiveness of combination targeted therapy (mirdametinib + BGB-3245) in people with advanced, metastatic or inoperable solid cancer who have had prior treatmentA 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

Trial purpose

Medical clipboardCancer treatment

Tumor type

Multi-Cancer Multi-Cancer

Age

People18+

Clinical summary

Summary

This study will be conducted in two sequential parts: Part 1 dose escalation and Part 2 dose expansion. In all arms, both mirdametinib and BGB-3245 will be administered orally.

Part 1 is enrolling people with an oncogenic mutation or other genomic aberration of the MPAK pathway who will be assigned to receive different dose levels to test their safety and effectiveness.

Part 2 has three cohorts that will enrol people with different types of cancer.

  • Part 2 Cohort A will recruit people with cutaneous melanoma harbouring NRAS mutations.
  • Part 2 Cohort B will recruit people with non-small cell lung cancer harbouring KRAS mutations.
  • Part 2 Cohort C will recruit people with non-small cell lung cancer or cutaneous melanoma harbouring BRAF Class II or Class III mutation or BRAF Fusion mutation.

Conditions

This trial is treating people with advanced solid cancers

Eligibility

Inclusion

  • 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

Exclusion

  • 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

Inclusion

  • Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
  • Your cancer has not spread to other parts of the body (localised).
  • You have been diagnosed with cancer, but have not received any treatment.
  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • You are able to swallow medication by mouth.

Exclusion

  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

Participating hospitals

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No longer recruiting (closed or complete) hospitals

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:

Trial sponsor

SpringWorks Therapeutics, Inc

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

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