NCT02122913

Brief Summary

This research study is done to test the safety of the drug larotrectinib in adult cancer patients. The drug may be used to treat cancer with a change in a particular gene (NTRK1, NTRK2 or NTRK3), because it blocks the action of these genes in cancer cells. The study also investigates how the drug is absorbed and processed in the human body. This is the first study to test larotrectinib in humans with cancer, for whom no other effective therapy exists.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
75

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started May 2014

Longer than P75 for phase_1

Geographic Reach
1 country

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 16, 2014

Completed
9 days until next milestone

First Posted

Study publicly available on registry

April 25, 2014

Completed
9 days until next milestone

Study Start

First participant enrolled

May 4, 2014

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2017

Completed
4.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 9, 2021

Completed
Last Updated

February 5, 2026

Status Verified

February 1, 2026

Enrollment Period

2.8 years

First QC Date

April 16, 2014

Last Update Submit

February 3, 2026

Conditions

Solid Tumors Harboring NTRK Fusion

Keywords

Advanced solid tumorsNeurotrophic tyrosine receptor kinase (NTRK)NTRK1NTRK2NTRK3Fusion PositiveTRK fusionTRKATRKBTRKCETV6

Outcome Measures

Primary Outcomes (4)

  • Number of participants with adverse events

    25 months

  • Severity of adverse events

    The severity of adverse events will be assesssed according to the NCI CTCAE version 4.03.

    25 months

  • Maximum tolerated dose (MTD)

    25 months

  • Recommended dose for dose expansion

    25 months

Secondary Outcomes (6)

  • Maximum concentration of larotrectinib in plasma (Cmax)

    Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1

  • Time to maximum concentration of larotrectinib in plasma (Tmax)

    Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1

  • Half-life of larotrectinib in plasma (t1/2)

    Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1

  • Area under the concentration versus time curve of larotrectinib in plasma (AUC)

    Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1

  • Overall Response Rate (ORR)

    Up to 60 months

  • +1 more secondary outcomes

Study Arms (7)

Tumor patients_Dose 1

EXPERIMENTAL

Adult patients with solid tumors receiving 50 mg of BAY2757556 once daily (dose escalation cohort).

Drug: Larotrectinib (Vitrakvi, BAY2757556)

Tumor patients_Dose 2

EXPERIMENTAL

Adult patients with solid tumors receiving 100 mg of BAY2757556 once daily (dose escalation cohort).

Drug: Larotrectinib (Vitrakvi, BAY2757556)

Tumor patients_Dose 3

EXPERIMENTAL

Adult patients with solid tumors receiving 100 mg of BAY2757556 twice daily (dose escalation cohort).

Drug: Larotrectinib (Vitrakvi, BAY2757556)

Tumor patients_Dose 4

EXPERIMENTAL

Adult patients with solid tumors receiving 200 mg of BAY2757556 once daily (dose escalation cohort).

Drug: Larotrectinib (Vitrakvi, BAY2757556)

Tumor patients_Dose 5

EXPERIMENTAL

Adult patients with solid tumors receiving 150 mg of BAY2757556 twice daily (dose escalation cohort).

Drug: Larotrectinib (Vitrakvi, BAY2757556)

Tumor patients_Dose 6

EXPERIMENTAL

Adult patients with solid tumors receiving 200 mg of BAY2757556 twice daily (dose escalation cohort).

Drug: Larotrectinib (Vitrakvi, BAY2757556)

Tumor patients_Expansion

EXPERIMENTAL

Adults patients with solid tumors and neurotrophic tyrosine kinase (NTRK) genes or proteins of types 1 - 3 (dose expansion cohort). Patients receive either the recommended or maximum tolerated dose of BAY2757556 as determined in the dose escalation part.

Drug: Larotrectinib (Vitrakvi, BAY2757556)

Interventions

Larotrectinib (Vitrakvi, BAY2757556)DRUG

BAY2757556 will be administered orally as capsule or in liquid form over continuous 28-day cycles.

Also known as: LOXO-101
Tumor patients_Dose 1Tumor patients_Dose 2Tumor patients_Dose 3Tumor patients_Dose 4Tumor patients_Dose 5Tumor patients_Dose 6Tumor patients_Expansion

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Adult patients with a locally advanced or metastatic solid tumor that has progressed or was nonresponsive to available therapies, are unfit for standard chemotherapy or for which no standard or available curative therapy exists
  • Proof of a malignancy harboring a NTRK fusion
  • Eastern Cooperative Oncology Group (ECOG) score of 0, 1 or 2 and a life expectancy of at least 3 months
  • Adequate hematologic, hepatic, and renal function

You may not qualify if:

  • Patients with unstable primary central-nervous-system tumors or metastasis, exceptions possible
  • Clinically significant active cardiovascular disease or history of myocardial infarction
  • Active uncontrolled systemic bacterial, viral, or fungal infection
  • Current treatment with a strong CYP3A4 inhibitor or inducer
  • Pregnancy or lactation

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

UCHealth Cancer Center - Anschutz Medical Campus - University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Mass General Cancer Center

Boston, Massachusetts, 02114, United States

Location

UH Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

OHSU Hospital - Neurology

Portland, Oregon, 97239, United States

Location

Hospital of the University of Pennsylvania - Radiology

Philadelphia, Pennsylvania, 19104, United States

Location

UPMC Mercy - Oncology

Pittsburgh, Pennsylvania, 15219, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center - Texas Medical Center

Houston, Texas, 77030, United States

Location

Related Publications (14)

  • Waguespack SG, Drilon A, Lin JJ, Brose MS, McDermott R, Almubarak M, Bauman J, Casanova M, Krishnamurthy A, Kummar S, Leyvraz S, Oh DY, Park K, Sohal D, Sherman E, Norenberg R, Silvertown JD, Brega N, Hong DS, Cabanillas ME. Efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma. Eur J Endocrinol. 2022 Apr 29;186(6):631-643. doi: 10.1530/EJE-21-1259.

    PMID: 35333737BACKGROUND

  • Brose MS, Westphalen CB, Pan X, Bernard-Gauthier V, Kurtinecz M, Guo H, Aris V, Brett NR, Majdi A, Subbiah V, Pennell NA, Kehl KL, Drilon A. Larotrectinib Compared With Real-World Non-Tropomyosin Receptor Kinase Inhibitor Therapies in Patients With Tropomyosin Receptor Kinase Fusion Cancer. JCO Precis Oncol. 2025 Apr;9:e2400500. doi: 10.1200/PO-24-00500. Epub 2025 Apr 23.

    PMID: 40267388DERIVED

  • Subbiah V, Burris HA 3rd, Kurzrock R. Revolutionizing cancer drug development: Harnessing the potential of basket trials. Cancer. 2024 Jan;130(2):186-200. doi: 10.1002/cncr.35085. Epub 2023 Nov 7.

    PMID: 37934000DERIVED

  • Kummar S, Shen L, Hong DS, McDermott R, Keedy VL, Casanova M, Demetri GD, Dowlati A, Melcon SG, Lassen UN, Leyvraz S, Liu T, Moreno V, Patel J, Patil T, Mallick AB, Sousa N, Tahara M, Ziegler DS, Norenberg R, Arvis P, Brega N, Drilon A, Tan DSW. Larotrectinib efficacy and safety in adult patients with tropomyosin receptor kinase fusion sarcomas. Cancer. 2023 Dec 1;129(23):3772-3782. doi: 10.1002/cncr.35036. Epub 2023 Sep 28.

    PMID: 37769113DERIVED

  • Bokemeyer C, Paracha N, Lassen U, Italiano A, Sullivan SD, Marian M, Brega N, Garcia-Foncillas J. Survival Outcomes of Patients With Tropomyosin Receptor Kinase Fusion-Positive Cancer Receiving Larotrectinib Versus Standard of Care: A Matching-Adjusted Indirect Comparison Using Real-World Data. JCO Precis Oncol. 2023 Jan;7:e2200436. doi: 10.1200/PO.22.00436.

    PMID: 36689698DERIVED

  • Rudzinski ER, Drilon A, Moore A, Spinosa S, Willi M, Laetsch TW. Testing methods to diagnose TRK fusion cancer - a plain language summary and patient perspective. Future Oncol. 2022 Dec;18(38):4141-4151. doi: 10.2217/fon-2022-0863. Epub 2023 Jan 6.

    PMID: 36606522DERIVED

  • Le X, Baik C, Bauman J, Gilbert J, Brose MS, Grilley-Olson JE, Patil T, McDermott R, Raez LE, Johnson JM, Shen L, Tahara M, Ho AL, Norenberg R, Dima L, Brega N, Drilon A, Hong DS. Larotrectinib Treatment for Patients With TRK Fusion-Positive Salivary Gland Cancers. Oncologist. 2022 May 10;29(6):e779-88. doi: 10.1093/oncolo/oyac080. Online ahead of print.

    PMID: 35536733DERIVED

  • 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.

    PMID: 35085007DERIVED

  • 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.

    PMID: 33467570DERIVED

  • 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.

    PMID: 33435412DERIVED

  • 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.

    PMID: 32105622DERIVED

  • Hong DS, Bauer TM, Lee JJ, Dowlati A, Brose MS, Farago AF, Taylor M, Shaw AT, Montez S, Meric-Bernstam F, Smith S, Tuch BB, Ebata K, Cruickshank S, Cox MC, Burris HA 3rd, Doebele RC. Larotrectinib in adult patients with solid tumours: a multi-centre, open-label, phase I dose-escalation study. Ann Oncol. 2019 Feb 1;30(2):325-331. doi: 10.1093/annonc/mdy539.

    PMID: 30624546DERIVED

  • 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.

    PMID: 29466156DERIVED

  • Doebele RC, Davis LE, Vaishnavi A, Le AT, Estrada-Bernal A, Keysar S, Jimeno A, Varella-Garcia M, Aisner DL, Li Y, Stephens PJ, Morosini D, Tuch BB, Fernandes M, Nanda N, Low JA. An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101. Cancer Discov. 2015 Oct;5(10):1049-57. doi: 10.1158/2159-8290.CD-15-0443. Epub 2015 Jul 27.

    PMID: 26216294DERIVED

Related Links

MeSH Terms

Interventions

larotrectinib

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR
Expanded Access
Yes

Study Record Dates

First Submitted

April 16, 2014

First Posted

April 25, 2014

Study Start

May 4, 2014

Primary Completion

February 1, 2017

Study Completion

April 9, 2021

Last Updated

February 5, 2026

Record last verified: 2026-02

Locations

US(8)