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History of Changes for Study: NCT03215511
Phase 1/2 Study of LOXO-195 in Patients With Previously Treated NTRK Fusions or Non-fusion NTRK Cancers
Latest version (submitted November 28, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 July 10, 2017 None (earliest Version on record)
2 July 27, 2017 Study Status
3 August 24, 2017 Contacts/Locations and Study Status
4 February 27, 2018 Outcome Measures, Eligibility, Conditions, Study Description, Study Status, Study Identification, Contacts/Locations, Arms and Interventions, Study Design and Sponsor/Collaborators
5 May 30, 2018 Study Status and Contacts/Locations
6 August 9, 2018 Outcome Measures, Study Status, Contacts/Locations and Eligibility
7 November 9, 2018 Contacts/Locations and Study Status
8 November 26, 2018 Contacts/Locations and Study Status
9 January 24, 2019 Contacts/Locations and Study Status
10 May 3, 2019 Study Status and Contacts/Locations
11 June 4, 2019 Study Status and Contacts/Locations
12 July 1, 2019 Study Identification, Sponsor/Collaborators and Study Status
13 July 5, 2019 Contacts/Locations, Outcome Measures, Arms and Interventions, Study Status, Study Identification, IPDSharing, Study Design, Conditions, Study Description and Eligibility
14 August 2, 2019 Study Status
15 August 30, 2019 Contacts/Locations, Eligibility and Study Status
16 September 26, 2019 Study Status, Contacts/Locations and Outcome Measures
17 October 23, 2019 Contacts/Locations and Study Status
18 December 11, 2019 Study Status
19 January 8, 2020 Study Status
20 February 7, 2020 Outcome Measures, Arms and Interventions, Study Description, Study Status, Study Identification, Contacts/Locations, Eligibility and Study Design
21 March 3, 2020 Study Status and Contacts/Locations
22 April 2, 2020 Contacts/Locations and Study Status
23 April 29, 2020 Study Description and Study Status
24 May 19, 2020 Study Status
25 June 15, 2020 Study Status and Contacts/Locations
26 July 14, 2020 Study Status
27 August 10, 2020 Study Status
28 September 7, 2020 Study Status
29 October 15, 2020 Study Status and Contacts/Locations
30 November 12, 2020 Study Status and Contacts/Locations
31 December 7, 2020 Study Status, Contacts/Locations, Eligibility and Study Description
32 January 5, 2021 Study Status and Contacts/Locations
33 February 7, 2021 Contacts/Locations and Study Status
34 March 17, 2021 Study Status and Contacts/Locations
35 April 15, 2021 Study Status
36 May 18, 2021 Study Status and Contacts/Locations
37 June 17, 2021 Study Status
38 July 19, 2021 Study Status
39 August 25, 2021 Study Status and Contacts/Locations
40 September 10, 2021 Recruitment Status, Study Status and Contacts/Locations
41 October 12, 2021 Study Status and Contacts/Locations
42 November 9, 2021 Study Status
43 January 10, 2022 Study Status and Contacts/Locations
44 February 11, 2022 Study Status
45 March 11, 2022 Study Status
46 April 8, 2022 Study Status
47 May 9, 2022 Study Status
48 June 15, 2022 Study Status and Study Design
49 August 2, 2022 Study Status
50 August 18, 2022 Study Status
51 September 19, 2022 Study Status and IPDSharing
52 November 2, 2022 Outcome Measures, Arms and Interventions, Study Status, IPDSharing, References, Eligibility, Study Design, Study Description and Study Identification
53 November 28, 2022 Study Status
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Study NCT03215511
Submitted Date:  July 10, 2017 (v1)

Open or close this module Study Identification
Unique Protocol ID: LOXO-EXT-17005
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
Secondary IDs:
Open or close this module Study Status
Record Verification: July 2017
Overall Status: Recruiting
Study Start: July 2017
Primary Completion: August 2019 [Anticipated]
Study Completion: December 2019 [Anticipated]
First Submitted: June 30, 2017
First Submitted that
Met QC Criteria:
July 10, 2017
First Posted: July 12, 2017 [Actual]
Last Update Submitted that
Met QC Criteria:
July 10, 2017
Last Update Posted: July 12, 2017 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Loxo Oncology, Inc.
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief Summary: 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.
Open or close this module Conditions
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
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
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1/Phase 2
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 120 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: LOXO-195
Phase 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
Drug: LOXO-195
Oral LOXO-195
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Maximum Tolerated Dose (MTD)
[ Time Frame: The first 28 days of treatment (Cycle 1) ]

For Phase 1
2. Recommended dose for further study
[ Time Frame: The first 28 days of treatment (Cycle 1) and every cycle (28 days) for approximately 12 months (or earlier if the patient discontinues from the study) ]

For Phase 1
3. Best overall response of confirmed PR or CR by independent radiology review in NTRK fusion cancer patients previously treated with TRK inhibitor who have progressed
[ 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 ]

For Phase 2
Secondary Outcome Measures:
1. 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) ]

For Phase 1 and Phase 2
2. 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) ]

For Phase 1 and Phase 2
3. 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) ]

For Phase 1 and Phase 2
4. 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) ]

For Phase 1 and Phase 2
5. 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) ]

For Phase 1 and Phase 2
6. 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 ]

For Phase 1
7. 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 ]

For Phase 1
8. 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 ]

For Phase 2
9. 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 ]

For Phase 2
10. 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 ]

For Phase 2
11. 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 ]

For Phase 2
12. 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 ]

For Phase 2
13. Overall survival (OS)
[ Time Frame: Up to 24 months ]

For Phase 2
14. Clinical benefit rate (CBR)
[ Time Frame: Up to 24 months ]

For Phase 2
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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.
Open or close this module Contacts/Locations
Central Contact Person: Patient Advocacy
Telephone: 1-855-NTRK-123
Email: clinicaltrials@loxooncology.com
Study Officials: Nora Ku, MD
Study Director
Senior Medical Director, Loxo Oncology
Locations: United States, New York
Memorial Sloan Kettering Cancer Center
[Recruiting]
New York, New York, United States, 10065
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Links:
Available IPD/Information:

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