A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK-fusion Positive Solid Tumors (NAVIGATE)

A Study to Learn How Well the Drug Larotrectinib Works in Adults With Different Solid Cancers With a Change in the Genes Called NTRK Fusion

This research study is done to test how well different types of cancer respond to the drug called larotrectinib. The cancer must have a change in a particular gene (NTRK1, NTRK2 or NTRK3). Larotrectinib is a drug that blocks the actions of these NTRK genes in cancer cells and can therefore be used to treat cancer.

Study Overview

• Status: Completed
• Conditions: Solid Tumors Harboring NTRK Fusion
• Intervention / Treatment: Drug: BAY2757556 (Larotrectinib, Vitrakvi)

Detailed Description

The primary objective of this study is to investigate the efficacy of larotrectinib for the treatment of advanced solid tumors harboring a fusion of neurotrophic tyrosine receptor kinase (NTRK) of types 1-3 in children and adults.

Secondary objectives comprise the efficacy and safety of larotrectinib in different NTRK-tumor types.

• Study Type: Interventional
• Enrollment (Actual): 215
• Phase: Phase 2

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Auton. de Buenos Aires
    • Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C11118AAT
      • Hospital Aleman
    • Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, TBC
      • Centro Estudios Médicos e Invest. Clínicas "Dr. N. Quirno"
    • CABA, Ciudad Auton. de Buenos Aires, Argentina, C1125 ABD
      • Fundación CENIT para la Investigación en Neurociencias
    • TBC, Ciudad Auton. de Buenos Aires, Argentina, C1019ABS
      • Centro Medico Austral
  • Tucumán Province
    • San Miguel de Tucumán, Tucumán Province, Argentina, T4000HXU
      • Centro Medico San Roque
• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2109
      • Macquarie University Hospital
  • Northern Territory
    • Tiwi, Northern Territory, Australia, 810
      • Royal Darwin Hospital
  • Western Australia
    • Subiaco, Western Australia, Australia, 6008
      • St John of God Healthcare
• Belgium
  • Brussels, Belgium, 1070
    • Institut Jules Bordet/Jules Bordet Instituut
• Brazil
  • Goiás
    • Goiânia, Goiás, Brazil, 74605-070
      • Hosp. Araujo Jorge da Associação de Combate ao Câncer
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30130-090
      • Cenantron Centro Avançado de Tratamento Oncológico, Ltda.
  • Rio de Janeiro
    • Rio de Janeiro, Rio de Janeiro, Brazil, 20081-250
      • Instituto Nacional do Câncer - INCA - HC II
    • Rio de Janeiro, Rio de Janeiro, Brazil, 20560-120
      • INCA - Hospital do Cancer III
    • Rio de Janeiro, Rio de Janeiro, Brazil, 22250-905
      • Oncoclínicas Rio de Janeiro S.A
  • São Paulo
    • Barretos/SP, São Paulo, Brazil, 14784-400
      • Fundação Pio XII - Hospital de Câncer de Barretos
    • São Paulo, São Paulo, Brazil, 01246-000
      • Instituto do Cancer do Estado de São Paulo
    • São Paulo, São Paulo, Brazil, 01323-001
      • Real e Benemerita Associacao Portuguesa de Beneficencia
    • São Paulo, São Paulo, Brazil, 03102-002
      • IBCC - Instituto Brasileiro de Controle do Cancer
    • São Paulo, São Paulo, Brazil, 01409-000
      • Hospital Sírio Libanês
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
• China
  • Shanghai, China, 200032
    • Zhongshan Hospital, Fudan University - Oncology Department
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital - Oncology Department
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Sun yat-sen University Cancer Center
  • Sichuan
    • Chengdu, Sichuan, China, MISSING
      • Sichuan University West China Hospital
• Colombia
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia, 111511
      • Instituto Nacional de Cancerología INC Colombia
  • Departamento de Córdoba
    • Montería, Departamento de Córdoba, Colombia, 230002
      • Oncomedica S.A.
  • Santander Department
    • Floridablanca, Santander Department, Colombia, 681004
      • Fundación Oftalmológica de Santander Carlos Ardila Lule
• Czechia
  • Olomouc, Czechia, 77900
    • Fakultni Nemocnice Olomouc
• Denmark
  • Copenhagen OE, Denmark, 2100
    • Rigshospitalet - Kræftbehandling
• France
  • Besançon, France, 25030
    • Hôpital Jean Minjoz
  • Bordeaux, France, 33000
    • Institut Bergonie - Unicancer Nouvelle Aquitaine - Service Oncologie medicale
  • Nice, France, 06100
    • Centre Antoine Lacassagne - Departement Oncologie
  • Paris, France, 75012
    • Hopital Saint Antoine APHP - Departement Oncologie
  • Paris, France, 75013
    • APHP-Hopital la Pitie Salpetriere-Departement oncologie
  • Poitiers, France, 86021
    • Hôpital de la Milétrie
  • Saint-Herblain, France, 44800
    • Institut de Cancerologie Ouest - Saint-Herblain
  • Strasbourg, France, 67200
    • ICANS - Institut de Cancerologie de Strasbourg Europe - service oncologie medicale
• Germany
  • State of Berlin
    • Berlin, State of Berlin, Germany, 12203
      • Charité Comprehensive Cancer Center (CCCC)
• India
  • Odisha
    • Bhubaneswar, Odisha, India, 751019
      • All India Institute of Medical Sciences
  • Puducherry
    • Gorimedu, Puducherry, India, 605006
      • Jawaharlal Institute Of Postgraduate Medical Education and R
• Ireland
  • Dublin, Ireland, TBC
    • St Vincents University Hospital
• Italy
  • Campania
    • Avellino, Campania, Italy, 83100
      • A.O.R.N. San Giuseppe Moscati
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • A.O.U. di Bologna Policlinico S.Orsola Malpighi
  • Friuli Venezia Giulia
    • Udine, Friuli Venezia Giulia, Italy, 33038
      • A.S.U. Friuli Centrale - A. Regionale Coordinamento Salute
  • Lazio
    • Rome, Lazio, Italy, 144
      • IRCCS Istituti Fisioterapici Ospitalieri - IFO
  • Lombardy
    • Milan, Lombardy, Italy, 20141
      • Istituto Europeo di Oncologia s.r.l
  • Veneto
    • Padova, Veneto, Italy, 35128
      • Istituto Oncologico Veneto
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 466-8560
      • Nagoya University Hospital
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
  • Tokyo
    • Koto-ku, Tokyo, Japan, 135-8550
      • The Cancer Institute Hospital of JFCR
• Portugal
  • Porto District
    • Porto, Porto District, Portugal, 4200-072
      • IPO Porto
• Russia
  • Arkhangelsk, Russia, 163045
    • Arkhangelsk Clinical Oncology Dispensary
  • Kazan', Russia, 420029
    • Republican Clinical Oncology Dispensary Kazan
  • Moscow, Russia, 115478
    • Russian Oncological Scientific Center n.a. N.N. Blokhin RAMS
  • Moscow, Russia, 119991
    • 1st Moscow State Medical University n.a. I.M.Sechenov
  • Nizhny Novgorod, Russia, 603006
    • Clinical Diagnostical Center
  • Saint Petersburg, Russia, 197758
    • St. Petersburg Clinical Onc. Cent. of Spec. Types of Care
• Singapore
  • Singapore, Singapore, 168583
    • National Cancer Center Singapore - Oncology Department
• Slovakia
  • Bratislava, Slovakia, 833 10
    • Narodny onkologicky ustav
  • Bratislava, Slovakia, 812 50
    • Onkologicky Ustav Svatej Alzbety, s.r.o.
• South Korea
  • Seoul, South Korea, 06351
    • Samsung Medical Center - Oncology Department
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, South Korea, 3080
      • Seoul National University Hospital
    • Seoul, Seoul Teugbyeolsi, South Korea, 03722
      • Severance Hospital, Yonsei University Health System
    • Seoul, Seoul Teugbyeolsi, South Korea, 05505
      • Asan Medical Center-Oncololy
• Spain
  • Barcelona
    • Barcelona, Barcelona, Spain, 08003
      • Hospital del Mar
    • Barcelona, Barcelona, Spain, 08035
      • Ciutat Sanitaria i Universitaria de la Vall d'Hebron
  • L Hospitalet de Llobregat
    • Barcelona, L Hospitalet de Llobregat, Spain, 8907
      • Institut Catala D'oncologia - Oncologia
  • Madrid
    • Madrid, Madrid, Spain, 28050
      • Centro Integral Oncologico Clara Campal
    • Madrid, Madrid, Spain, 28040
      • Hospital Universitario Fundacion Jimenez Diaz
    • Madrid, Madrid, Spain, 28007
      • Hospital General Universitario Gregorio Maranon | Oncologia
• Sweden
  • Stockholm, Sweden, 171 76
    • Karolinska Universitetssjukhuset Solna - Tema Cancer
• Taiwan
  • Taipei, Taiwan, 114
    • Tri-Service General Hospital
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 6800
    • Health Ministry Of Türkiye Republic Ankara Bilkent City Hospital
  • Edirne, Turkey (Türkiye), 22030
    • Trakya Univ. Tip Fak.
  • Istanbul, Turkey (Türkiye), 34098
    • Istanbul Universitesi Cerrahpasa-Cerrahpasa Tip Fakultesi
  • Istanbul, Turkey (Türkiye), 34093
    • Istanbul Universitesi Istanbul Tip Fakultesi
  • Istanbul, Turkey (Türkiye), 34722
    • TC Saglik Bakanligi Goztepe ProfDr Suleyman Yalcin Sehir Has
  • Izmir, Turkey (Türkiye), 35360
    • Izmir Katip Celebi Universitesi Ataturk Egitim ve Arastirma
  • Kayseri, Turkey (Türkiye), 38039
    • Erciyes Universitesi Tip Fakultesi
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Center Palo Alto
    • Santa Monica, California, United States, 90404
      • UCLA Health Santa Monica Cancer Care
  • Florida
    • Pembroke Pines, Florida, United States, 33026
      • Memorial Cancer Institute at West
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center - Hyde Park - Hematology & Oncology
  • Massachusetts
    • Boston, Massachusetts, United States, 02114-2696
      • Mass General Cancer Center
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute - Oncology Department
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center New York - Main Campus
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • UNC Hospitals - UNC Lineberger Comprehensive Cancer Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic - Neurology
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Sidney Kimmel Cancer Center - Jefferson Health
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute - Sioux Falls
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center - Texas Medical Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch Cancer Center - Sloan Clinic 1
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • West Virginia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Locally-advanced or metastatic malignancy with an NTRK1, NTRK2, or NTRK3 gene fusion, identified through molecular assays as routinely performed at CLIA or other similarly-certified laboratories. Subjects who have an NTRK gene fusion identified in a lab where CLIA or equivalent certification cannot be confirmed by the Sponsor at the time of consent may have been enrolled in Cohort 9 as per protocol versions 1.0 - 8.0. From protocol version 9.0: CLIA or similar certification of the lab performing the fusion assay is required. However, patients may be included after discussion with the sponsor if the lab performing the fusion assay is not CLIA or similar certified.
• Subjects who have received prior standard therapy appropriate for their tumor type and stage of disease, or who have no satisfactory alternative treatments and in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy.

• Subjects must have at least one measurable lesion as defined by RECIST v1.1 (Eisenhauer et al. 2009). Subjects with solid tumors without RECIST v1.1 measurable disease (e.g., evaluable disease only) had been eligible for enrollment to Cohort 8 as per protocol versions 1.0 - 8.0, regardless of tumor type. Subjects with primary CNS tumors should meet the following criteria:

  1. Have received prior treatment including radiation and/or chemotherapy, with radiation completed > 12 weeks prior to C1D1 of therapy, as recommended or appropriate for that CNS tumor type.
  2. Have ≥ 1 site of bi-dimensionally measurable disease (confirmed by magnetic resonance imaging [MRI] and evaluable by RANO criteria), with the size of at least one of the measurable lesions ≥ 1 cm in each dimension and noted on more than one imaging slice.
  3. Imaging study performed within 28 days before enrollment. If on steroid therapy, the dose must be stable for at least 7 days immediately before and during the imaging study.

  4. Must be neurologically stable based on stable neurologic exam for 7 days prior to enrollment.

     For subjects eligible for enrollment to bone health cohort, inclusion criterion 3 is modified as the following:

  5. Subjects must have at least one lesion at baseline (measurable or non-measurable as defined by RECIST v1.1 or RANO criteria, as appropriate to tumor type).
  6. Subjects with primary CNS tumors must be neurologically stable based on stable neurologic exam for 7 days prior to enrollment.
• At least 18 years of age
• Performance Status: Eastern Cooperative Oncology Group (ECOG) score ≤ 3. If enrolled with primary CNS tumor to be assessed by RANO, Karnofsky Performance Score (KPS) ≥ 50%.
• Tumor tissue before treatment (mandatory). If neither fresh tissue can be obtained nor archival tissue is available patients might be enrolled after consultation with the sponsor.

• Adequate organ function as defined by the following criteria:

  1. Serum AST and serum ALT < 2.5 x upper limit of normal (ULN), or AST and ALT < 5 x ULN if liver function abnormalities are due to underlying malignancy
  2. Total bilirubin < 2.5 x ULN, except in the setting of biliary obstruction. Subjects with a known history of Gilberts Disease and an isolated elevation of indirect bilirubin are eligible
  3. Serum creatinine < 2.0 x ULN OR an estimated glomerular filtration rate ≥ 30 mL/minute using the Cockcroft-Gault formula: (140- age) x body weight (kg) x 0.85 (if female)/serum creatinine (mg/dL) x 72 with either result acceptable for enrollment.
• Ability to comply (or for guardian to ensure compliance) with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation.
• Willingness of men and women of reproductive potential to use double effective birth control methods, defined as one used by the subject and another by his/her partner, for the duration of treatment and for 1 month following study completion.
• For subjects eligible for enrollment to bone health cohort only: life expectancy of at least 6 months, based on investigator assessment.

Exclusion Criteria:

• Investigational agent or anticancer therapy within 2 weeks prior to the planned start of larotrectinib or 5 half-lives, whichever is shorter, and without recovery of acute and/or clinically significant toxicities from that therapy.
• Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting TRK. Subjects who received less than 28 days of treatment and discontinued because of intolerance or toxicity are eligible.
• Symptomatic or unstable brain metastases. (Note: Subjects with asymptomatic brain metastases are eligible to participate in the study.) Subjects with primary CNS tumors are eligible.
• Uncontrolled concurrent malignancy that would limit assessment of efficacy of larotrectinib. Allowed conditions may include, but are not limited to in situ cancers of cervix, breast, or skin, superficial bladder cancer, limited-stage prostate cancer, and basal or squamous cancers of the skin.

• Active uncontrolled systemic bacterial, viral, or fungal infection CTCAE grade ≥ 2; unstable cardiovascular disease, or other systemic disease that would limit compliance with study procedures. Unstable cardiovascular disease is defined as:

  1. In adults, persistently uncontrolled hypertension defined as systolic blood pressure (BP) > 150 mmHg and/or diastolic BP > 100 mmHg despite antihypertensive therapy.
  2. Myocardial infarction within 3 months of screening.
  3. Stroke within 3 months of screening.
• Inability to discontinue treatment with a strong CYP3A4 inhibitor or inducer
• Currently recovering from AEs/ ADRs due to previous treatments (excluding alopecia). Inclusion is only advised once the AE/ADR resolves or recovers to baseline or at least to CTCAE grade 1.
• Known or suspected hypersensitivity against the active substance or any of the ingredients of the IMP.
• Known history of HIV infection. All patients must be screened for HIV up to 28 days prior to study drug start using a blood test for HIV according to local regulations.
• HBV or HCV infection. All patients must be screened for HBV and HCV up to 28 days prior to study drug start using the routine hepatitis virus laboratorial panel. Patients positive for HBsAg or HBcAb will be eligible if they are negative for HBVDNA. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1_NSCLC; Patients with solid non-small cell lung cancer (NSCLC) harboring NTRK fusions (arm closed)	Drug: BAY2757556 (Larotrectinib, Vitrakvi); Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles.; Other Names: LOXO-101
Experimental: Arm 2_Thyroid; Patients with solid thyroid tumors harboring NTRK fusions (arm closed)	Drug: BAY2757556 (Larotrectinib, Vitrakvi); Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles.; Other Names: LOXO-101
Experimental: Arm 3_Sarcoma; Patients with soft-tissue sarcoma harboring NTRK fusions (arm closed)	Drug: BAY2757556 (Larotrectinib, Vitrakvi); Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles.; Other Names: LOXO-101
Experimental: Arm 4_Colorectal; Patients with solid colorectal tumors harboring NTRK fusions (arm closed)	Drug: BAY2757556 (Larotrectinib, Vitrakvi); Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles.; Other Names: LOXO-101
Experimental: Arm 5_Salivary; Patients with solid salivary tumors harboring NTRK fusions (arm closed)	Drug: BAY2757556 (Larotrectinib, Vitrakvi); Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles.; Other Names: LOXO-101
Experimental: Arm 6_Biliary; Patients with solid biliary tumors harboring NTRK fusions (arm closed)	Drug: BAY2757556 (Larotrectinib, Vitrakvi); Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles.; Other Names: LOXO-101
Experimental: Arm 7_Primary CNS; Patients with solid tumors in the primary central nervous system (CNS) harboring NTRK fusions (arm closed)	Drug: BAY2757556 (Larotrectinib, Vitrakvi); Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles.; Other Names: LOXO-101
Experimental: Arm 8_Other tumors; Patients with e.g. kidney cancer, squamous cell cancer of head or neck or ovarian solid tumors harboring NTRK fusions (arm closed)	Drug: BAY2757556 (Larotrectinib, Vitrakvi); Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles.; Other Names: LOXO-101
Experimental: Arm 9_Solid tumors without confirmed NTRK fusion; Patients eligible for arms 1 to 8, but with documented NTRK fusion from a laboratory where CLIA or equivalent certification cannot be confirmed by the sponsor at the time of consent (arm closed)	Drug: BAY2757556 (Larotrectinib, Vitrakvi); Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles.; Other Names: LOXO-101
Experimental: Arm 11_Bone health cohort; Patients with all tumor types harboring NTRK fusions, not eligible for the main prospective cohort, including patients with non-measurable disease	Drug: BAY2757556 (Larotrectinib, Vitrakvi); Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles.; Other Names: LOXO-101
Experimental: Arm 10_Prospective cohort; Patients with melanoma, non secretory breast and colorectal cancer or other tumor types harboring NTRK fusions, except soft tissue sarcoma, salivary gland and thyroid cancer (arm closed)	Drug: BAY2757556 (Larotrectinib, Vitrakvi); Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles.; Other Names: LOXO-101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Best overall response of confirmed complete response (CR) or partial response (PR) as determined by an independent radiology review committee using RECIST v1.1 or RANO criteria, as appropriate to tumor type.	Up to 120 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with safety-relevant changes in clinical parameters or vital signs after drug administration		Up to 120 months
Severity of safety-relevant changes in clinical parameters or vital signs after drug administration		Up to 120 months
Best overall response of confirmed CR or PR as determined by the treating Investigator using RECIST v1.1 or RANO criteria, as appropriate to tumor type		Up to 120 months
Duration of response (DOR): determined for subjects with best overall response of confirmed CR or PR by 1) an independent radiology review committee and 2) the treating Investigator	Duration of response is the number of months from the start of confirmed complete response or partial response to disease progression or death. Complete response, partial response and disease progression are assessed by an independent radiology committee (IRC).	Up to 120 months
Clinical benefit rate (CBR): best overall response of confirmed CR, PR, or stable disease lasting 16 or more weeks following the initiation of Larotrectinib		Up to 120 months
Rate of subjects that have any tumor regression as a best response, measured as shrinkage of target lesions		Up to 120 months
PFS: Number of months from initiation of larotrectinib to the earlier of disease progression or death due to any cause		Up to 120 months
Overall Survival (OS): Number of months from the initiation of larotrectinib to the date of death due to any cause.		Up to 120 months
Comparison of PFS following initiation of larotrectinib to that following the line of therapy immediately preceding larotrectinib in each subject who has received prior therapy		Up to 120 months
Number of subjects with AEs categorized by severity. (including all, serious, and those considered treatment related.)		Up to 120 months
Concordance coefficient	Concordance of prior molecular profiling that detected an NTRK fusion within the subject's tumor with the diagnostic test being evaluated by the Sponsor.	Up to 120 months

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Doz F, van Tilburg CM, Geoerger B, Hojgaard M, Ora I, Boni V, Capra M, Chisholm J, Chung HC, DuBois SG, Gallego-Melcon S, Gerber NU, Goto H, Grilley-Olson JE, Hansford JR, Hong DS, Italiano A, Kang HJ, Nysom K, Thorwarth A, Stefanowicz J, Tahara M, Ziegler DS, Gavrilovic IT, Norenberg R, Dima L, De La Cuesta E, Laetsch TW, Drilon A, Perreault S. Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors. Neuro Oncol. 2022 Jun 1;24(6):997-1007. doi: 10.1093/neuonc/noab274.
• Bebb DG, Banerji S, Blais N, Desmeules P, Gill S, Grin A, Feilotter H, Hansen AR, Hyrcza M, Krzyzanowska M, Melosky B, Noujaim J, Purgina B, Ruether D, Simmons CE, Soulieres D, Torlakovic EE, Tsao MS. Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Adults. Curr Oncol. 2021 Jan 15;28(1):523-548. doi: 10.3390/curroncol28010053.
• Perreault S, Chami R, Deyell RJ, El Demellawy D, Ellezam B, Jabado N, Morgenstern DA, Narendran A, Sorensen PHB, Wasserman JD, Yip S. Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Pediatric Patients. Curr Oncol. 2021 Jan 9;28(1):346-366. doi: 10.3390/curroncol28010038.
• Hong DS, DuBois SG, Kummar S, Farago AF, Albert CM, Rohrberg KS, van Tilburg CM, Nagasubramanian R, Berlin JD, Federman N, Mascarenhas L, Geoerger B, Dowlati A, Pappo AS, Bielack S, Doz F, McDermott R, Patel JD, Schilder RJ, Tahara M, Pfister SM, Witt O, Ladanyi M, Rudzinski ER, Nanda S, Childs BH, Laetsch TW, Hyman DM, Drilon A. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol. 2020 Apr;21(4):531-540. doi: 10.1016/S1470-2045(19)30856-3. Epub 2020 Feb 24.
• Drilon A, Laetsch TW, Kummar S, DuBois SG, Lassen UN, Demetri GD, Nathenson M, Doebele RC, Farago AF, Pappo AS, Turpin B, Dowlati A, Brose MS, Mascarenhas L, Federman N, Berlin J, El-Deiry WS, Baik C, Deeken J, Boni V, Nagasubramanian R, Taylor M, Rudzinski ER, Meric-Bernstam F, Sohal DPS, Ma PC, Raez LE, Hechtman JF, Benayed R, Ladanyi M, Tuch BB, Ebata K, Cruickshank S, Ku NC, Cox MC, Hawkins DS, Hong DS, Hyman DM. Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med. 2018 Feb 22;378(8):731-739. doi: 10.1056/NEJMoa1714448.
• Drilon A, Tan DSW, Lassen UN, Leyvraz S, Liu Y, Patel JD, Rosen L, Solomon B, Norenberg R, Dima L, Brega N, Shen L, Moreno V, Kummar S, Lin JJ. Efficacy and Safety of Larotrectinib in Patients With Tropomyosin Receptor Kinase Fusion-Positive Lung Cancers. JCO Precis Oncol. 2022 Jan;6:e2100418. doi: 10.1200/PO.21.00418.
• Lee YA, Lee H, Im SW, Song YS, Oh DY, Kang HJ, Won JK, Jung KC, Kwon D, Chung EJ, Hah JH, Paeng JC, Kim JH, Choi J, Kim OH, Oh JM, Ahn BC, Wirth LJ, Shin CH, Kim JI, Park YJ. NTRK and RET fusion-directed therapy in pediatric thyroid cancer yields a tumor response and radioiodine uptake. J Clin Invest. 2021 Sep 15;131(18):e144847. doi: 10.1172/JCI144847.
• O'Reilly EM, Hechtman JF. Tumour response to TRK inhibition in a patient with pancreatic adenocarcinoma harbouring an NTRK gene fusion. Ann Oncol. 2019 Nov 1;30(Suppl_8):viii36-viii40. doi: 10.1093/annonc/mdz385. Epub 2019 Dec 24.
• Shi E, Chmielecki J, Tang CM, Wang K, Heinrich MC, Kang G, Corless CL, Hong D, Fero KE, Murphy JD, Fanta PT, Ali SM, De Siena M, Burgoyne AM, Movva S, Madlensky L, Heestand GM, Trent JC, Kurzrock R, Morosini D, Ross JS, Harismendy O, Sicklick JK. FGFR1 and NTRK3 actionable alterations in "Wild-Type" gastrointestinal stromal tumors. J Transl Med. 2016 Dec 14;14(1):339. doi: 10.1186/s12967-016-1075-6.
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Helpful Links

• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2015
• Primary Completion (Actual): September 29, 2025
• Study Completion (Actual): September 29, 2025

Study Registration Dates

• First Submitted: October 12, 2015
• First Submitted That Met QC Criteria: October 13, 2015
• First Posted (Estimated): October 15, 2015

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Colorectal cancer; Non-small cell lung cancer; Breast cancer; Melanoma; Sarcoma; Thyroid cancer; NTRK1; NTRK2; NTRK3; Neurotrophic tyrosine receptor kinase (NTRK); Fusion Positive; TRK fusion; TRKA; TRKB; TRKC; ETV6; Salivary gland cancer; Biliary cancer; Central nervous system (CNS) Tumor
• Additional Relevant MeSH Terms: Endocrine System Diseases; Mouth Diseases; Stomatognathic Diseases; Neoplasms by Site; Intestinal Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Biliary Tract Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Lung Neoplasms; Skin Diseases; Breast Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Salivary Gland Diseases; Neuroendocrine Tumors; Neoplasms, Connective and Soft Tissue; Nevi and Melanomas; Skin Neoplasms; Thyroid Diseases; Mouth Neoplasms; Skin and Connective Tissue Diseases; Neoplasms; Biliary Tract Neoplasms; Colorectal Neoplasms; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Melanoma; Sarcoma; Thyroid Neoplasms; Salivary Gland Neoplasms; larotrectinib
• Other Study ID Numbers: 20289; LOXO-TRK-15002 (Other Identifier: Loxo Oncology, Inc); 2015-003582-28 (EudraCT Number); 2022-502667-38-00 (Other Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No