Clinical Trials /

Phase 1/2 Study of LOXO-195 in Patients With Previously Treated NTRK Fusion Cancers

NCT03215511

Description:

This is a Phase 1/2, multi-center, open-label study designed to evaluate the safety and efficacy of LOXO-195 when administered orally to patients age ≥ 1 month and older with NTRK fusion cancers treated with a prior TRK inhibitor.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 1/2 Study of LOXO-195 in Patients With Previously Treated NTRK Fusions or Non-fusion NTRK Cancers
  • Official Title: A Phase 1/ 2 Study of the TRK Inhibitor LOXO 195 in Adult Subjects With NTRK Fusion (Previously Treated) or Non-Fusion NTRK Altered Cancers

Clinical Trial IDs

  • ORG STUDY ID: LOXO-EXT-17005
  • NCT ID: NCT03215511

Conditions

  • Carcinoma, Non-Small-Cell Lung
  • Thyroid Neoplasms
  • Sarcoma
  • Colorectal Neoplasms
  • Salivary Gland Neoplasms
  • Biliary Tract Neoplasms
  • Brain Neoplasm, Primary
  • Breast Ductal Carcinoma NOS
  • Melanoma
  • Solid Tumors Cancer of Unknown Primary
  • Glioblastoma
  • Bile Duct Neoplasms
  • Astrocytoma
  • Head and Neck Squamous Cell Carcinoma
  • Pontine Glioma
  • Pancreatic Neoplasms
  • Ovarian Neoplasms
  • Carcinoma, Renal Cell
  • Cholangiocarcinoma
  • Skin Carcinoma
  • Carcinoma, Bronchogenic
  • Bronchial Neoplasms
  • Lung Neoplasms
  • Respiratory Tract Neoplasms
  • Thoracic Neoplasms
  • Neoplasms, Nerve Tissue
  • Nevi and Melanomas
  • Intestinal Neoplasms
  • Thyroid Cancer
  • GIST
  • Malignant Peripheral Nerve Sheath Tumors
  • Breast Secretory Carcinoma
  • Uterine Neoplasms

Interventions

DrugSynonymsArms
LOXO-195LOXO-195

Purpose

This is a Phase 1/2, multi-center, open-label study designed to evaluate the safety and efficacy of LOXO-195 when administered orally to patients with NTRK fusion cancers treated with prior TRK inhibition or non-fusion NTRK altered cancers regardless of prior kinase inhibitor treatment.

Detailed Description

      The trial will be conducted in 2 parts: dose escalation (Phase I ) and dose expansion (Phase
      2) . During Phase 1, patients with advanced solid tumors are eligible if the tumor has
      progressed following or has not adequately responded to standard therapy, or if the patient
      is intolerant of, or unlikely to benefit from or refuses standard therapy. Prior TRK
      inhibitor therapy is required for patients harboring an NTRK fusion. During Phase 2, the same
      patient population as designated for Phase 1 will be treated with the dose of LOXO-195 which
      has been identified during phase 1 to assess specified endpoints.
    

Trial Arms

NameTypeDescriptionInterventions
LOXO-195ExperimentalPhase 1- Dose Escalation and determination of MTD; Multiple dose levels of LOXO-195 to be evaluated Phase 2 - Treatment with LOXO-195 at the recommended dose from Phase 1 identified for further study
  • LOXO-195

Eligibility Criteria

        Key Inclusion Criteria:

          -  Advanced solid tumor for which, in the opinion of the Investigator, no other standard
             or investigational therapy offers greater benefit.

          -  A solid tumor diagnosis in the setting of:

               1. a documented NTRK fusion and a clinical history of relapse following a response
                  to a prior TRK inhibitor

               2. a documented NTRK fusion unresponsive to a prior TRK inhibitor

               3. a documented NTRK fusion and a clinical history of intolerance to a prior TRK
                  inhibitor

               4. a documented NTRK alteration other than a fusion, whether or not treated with a
                  prior TRK inhibitor

          -  Patients will be identified via a CLIA certified (or equivalent) laboratory

          -  Performance Status: Eastern Cooperative Oncology Group (ECOG) score ≤ 3. If enrolled
             with primary CNS tumor to be assessed by RANO, Karnofsky Performance Status (KPS) ≥
             50%

          -  Life expectancy > 4 weeks

          -  Adequate hematologic, hepatic and renal function.

          -  Patients with stable CNS primary tumor, brain metastases, or treated spinal cord
             compression are eligible if neurological symptoms and steroid use (if applicable) have
             been stable for 7 days prior to the first dose of LOXO-195

          -  Ability to receive study drug therapy orally

        Key Exclusion Criteria:

          -  Required treatment with certain strong CYP3A4 inhibitors or inducers.

          -  Clinically significant active cardiovascular disease or history of myocardial
             infarction within 6 months prior to planned start of LOXO-195 or prolongation of the
             QT interval corrected (QTcF) > 480 msec.

          -  Major surgery within 7 days of enrollment

          -  Uncontrolled systemic bacterial, fungal or viral infection

          -  Untreated/symptomatic leptomeningeal carcinomatosis, spinal cord compression, primary
             CNS metastases or primary CNS malignancy.

          -  Pregnancy or lactation.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD)
Time Frame:The first 28 days of treatment (Cycle 1)
Safety Issue:
Description:For Phase 1

Secondary Outcome Measures

Measure:Incidence of AEs
Time Frame:From the time of informed consent, for approximately 24 months (or earlier if the patient discontinues from the study), and through Safety Follow-up (28 days after the last dose)
Safety Issue:
Description:For Phase 1 and Phase 2
Measure:Severity of AEs
Time Frame:From the time of informed consent, for approximately 24 months (or earlier if the patient discontinues from the study), and through Safety Follow-up (28 days after the last dose)
Safety Issue:
Description:For Phase 1 and Phase 2
Measure:Duration of AEs
Time Frame:From the time of informed consent, for approximately 24 months (or earlier if the patient discontinues from the study), and through Safety Follow-up (28 days after the last dose)
Safety Issue:
Description:For Phase 1 and Phase 2
Measure:Changes in clinical laboratory results compared to baseline
Time Frame:For approximately 24 months (or earlier if the patient discontinues from the study), and through Safety Follow-up (28 days after the last dose)
Safety Issue:
Description:For Phase 1 and Phase 2
Measure:Changes in vital signs compared to baseline
Time Frame:For approximately 24 months (or earlier if the patient discontinues from the study), and through Safety Follow-up (28 days after the last dose)
Safety Issue:
Description:For Phase 1 and Phase 2
Measure:Best overall response of confirmed PR or CR by independent radiology review in NTRK fusion cancer patients previously treated with TRK inhibitor
Time Frame:Approximately every 8 weeks for one year, then every 12 weeks while on treatment, and every 12 weeks after the last dose (for up to 2 years) in patients who have not progressed
Safety Issue:
Description:For Phase 1
Measure:Best overall response of confirmed CR or PR as determined by treating investigators using RECIST v1.1 in patients with non-fusion NTRK altered cancers or RANO in patients with primary CNS malignancies.
Time Frame:Approximately every 8 weeks for one year, then every 12 weeks while on treatment, and every 12 weeks after the last dose (for up to 2 years) in patients who have not progressed
Safety Issue:
Description:For Phase 1
Measure:Best overall response of confirmed PR or CR using RECIST v1.1 or RANO criteria as appropriate in patients with non-fusion NTRK altered cancers who have demonstration of progression following or during receipt of previous anticancer therapy
Time Frame:Approximately every 8 weeks for one year, then every 12 weeks while on treatment, and every 12 weeks after the last dose (for up to 2 years) in patients who have not progressed
Safety Issue:
Description:For Phase 2
Measure:Best overall response of confirmed PR or CR using RECIST v1.1 or RANO criteria as appropriate in patients with documented NTRK alterations, including TRK fusions, who discontinued previous anticancer therapy including TRK inhibitors due to intolerance
Time Frame:Approximately every 8 weeks for one year, then every 12 weeks while on treatment, and every 12 weeks after the last dose (for up to 2 years) in patients who have not progressed
Safety Issue:
Description:For Phase 2
Measure:Duration or response (DOR) for patients with best overall response of confirmed CR or PR by an independent radiology review committee
Time Frame:Approximately every 8 weeks for one year, then every 12 weeks while on treatment, and every 12 weeks after the last dose (for up to 2 years) in patients who have not progressed
Safety Issue:
Description:For Phase 2
Measure:Duration or response (DOR) for patients with best overall response of confirmed CR or PR by the treating Investigator
Time Frame:Approximately every 8 weeks for one year, then every 12 weeks while on treatment, and every 12 weeks after the last dose (for up to 2 years) in patients who have not progressed
Safety Issue:
Description:For Phase 2
Measure:Progression-free survival (PFS)
Time Frame:Approximately every 8 weeks for one year, then every 12 weeks while on treatment, and every 12 weeks after the last dose (for up to 2 years) in patients who have not progressed
Safety Issue:
Description:For Phase 2
Measure:Overall survival (OS)
Time Frame:Up to 24 months
Safety Issue:
Description:For Phase 2
Measure:Clinical benefit rate (CBR)
Time Frame:Up to 24 months
Safety Issue:
Description:For Phase 2

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Loxo Oncology, Inc.

Trial Keywords

  • NTRK Fusion Positive
  • LOXO-195
  • Loxo
  • TRK
  • TRK Fusion
  • NTRK1
  • NTRK2
  • NTRK3
  • TRKA
  • TRKB
  • TRKC
  • NTRK
  • ETV6
  • fusion
  • tumors
  • CNS tumors
  • solid tumors
  • central nervous system tumors
  • advanced cancer
  • primary CNS tumor
  • Advanced CNS tumor
  • Metastatic CNS tumor
  • NTRK1 fusion
  • NTRK2 fusion
  • NTRK3 fusion
  • ETV6-NTRK3
  • ETV6 fusion
  • Metastatic cancer
  • Cancer of Unknown Primary Site

Last Updated

August 24, 2017