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Solid Tumors Harboring NTRK FusionPhase 1NCT02122913

A Study to Test the Safety of the Investigational Drug Larotrectinib in Adults That May Treat Cancer

A Phase 1 study testing Larotrectinib (Vitrakvi, BAY2757556) in people with Solid Tumors Harboring NTRK Fusion, run by Bayer at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumors Harboring NTRK Fusion
What is being tested?
Larotrectinib (Vitrakvi, BAY2757556)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
75 participants
Where
8 sitesUnited States
Study dates
4 May 2014to 9 Apr 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

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

    Aurora, Colorado, 80045

  • Mass General Cancer Center

    Boston, Massachusetts, 02114

  • UH Seidman Cancer Center

    Cleveland, Ohio, 44106

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

    Houston, Texas, 77030

  • SCRI Oncology Partners

    Nashville, Tennessee, 37203

  • Hospital of the University of Pennsylvania - Radiology

    Philadelphia, Pennsylvania, 19104

  • UPMC Mercy - Oncology

    Pittsburgh, Pennsylvania, 15219

  • OHSU Hospital - Neurology

    Portland, Oregon, 97239

Other trials in United States

About this study

Official title: A Phase 1 Study of the Oral TRK Inhibitor Larotrectinib in Adult Patients With Solid Tumors

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.

Read the detailed description

The trial will be conducted in 2 parts: an initial dose escalation phase of larotrectinib in subjects with advanced solid tumors will be followed by an expansion phase in subjects with solid tumors having a NTRK fusion.

The objectives of the study are to determine the safety, pharmacokinetic profile, recommended dose and efficacy of orally administered larotrectinib in patients with NTRK fusions.

Being tested
Larotrectinib (Vitrakvi, BAY2757556)
Keywords
Advanced solid tumors, Neurotrophic tyrosine receptor kinase (NTRK), NTRK1, NTRK2, NTRK3, Fusion Positive, TRK fusion, TRKA, TRKB, TRKC, ETV6

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Larotrectinib (Vitrakvi, BAY2757556)Drug

    Also called LOXO-101

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

Study groups in NCT02122913
Study groupRoleWhat they receive
Tumor patients_Dose 1ExperimentalAdult patients with solid tumors receiving 50 mg of BAY2757556 once daily (dose escalation cohort).
Receives: Drug: Larotrectinib (Vitrakvi, BAY2757556)
Tumor patients_Dose 2ExperimentalAdult patients with solid tumors receiving 100 mg of BAY2757556 once daily (dose escalation cohort).
Receives: Drug: Larotrectinib (Vitrakvi, BAY2757556)
Tumor patients_Dose 3ExperimentalAdult patients with solid tumors receiving 100 mg of BAY2757556 twice daily (dose escalation cohort).
Receives: Drug: Larotrectinib (Vitrakvi, BAY2757556)
Tumor patients_Dose 4ExperimentalAdult patients with solid tumors receiving 200 mg of BAY2757556 once daily (dose escalation cohort).
Receives: Drug: Larotrectinib (Vitrakvi, BAY2757556)
Tumor patients_Dose 5ExperimentalAdult patients with solid tumors receiving 150 mg of BAY2757556 twice daily (dose escalation cohort).
Receives: Drug: Larotrectinib (Vitrakvi, BAY2757556)
Tumor patients_Dose 6ExperimentalAdult patients with solid tumors receiving 200 mg of BAY2757556 twice daily (dose escalation cohort).
Receives: Drug: Larotrectinib (Vitrakvi, BAY2757556)
Tumor patients_ExpansionExperimentalAdults 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.
Receives: Drug: Larotrectinib (Vitrakvi, BAY2757556)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with adverse events

    Measured: 25 months

  2. Severity of adverse events

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

    Measured: 25 months

  3. Maximum tolerated dose (MTD)

    Measured: 25 months

  4. Recommended dose for dose expansion

    Measured: 25 months

Secondary outcomes (6)

  1. Maximum concentration of larotrectinib in plasma (Cmax)

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

  2. Time to maximum concentration of larotrectinib in plasma (Tmax)

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

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

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

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

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

  5. Overall Response Rate (ORR)

    Assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or Response Assessment in Neuro-Oncology (RANO) as appropriate

    Measured: Up to 60 months

  6. Duration of Response (DOR)

    Measured: Up to 60 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Apr 2014 (estimated)
  2. Study start4 May 2014
  3. Primary completion1 Feb 2017
  4. Study completion9 Apr 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
75 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02122913
Sponsor's protocol ID
20288
Other IDs
LOXO-TRK-14001
Status last verified
Feb 2026
First submitted
16 Apr 2014
Last updated
5 Feb 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided: Availability of this study's data will 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.clinicalstudydatarequest.com 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 Study sponsors section of the portal.
Expanded access
Available

Publications

  • 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.

    PubMed 35333737

  • 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.

    PubMed 40267388

  • 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.

    PubMed 37934000

  • 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.

    PubMed 37769113

  • 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.

    PubMed 36689698

  • 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.

    PubMed 36606522

  • 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.

    PubMed 35536733

  • 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.

    PubMed 35085007

  • 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.

    PubMed 33467570

  • 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.

    PubMed 33435412

  • 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.

    PubMed 32105622

  • 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.

    PubMed 30624546

  • 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.

    PubMed 29466156

  • 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.

    PubMed 26216294

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Larotrectinib (Vitrakvi, BAY2757556) in people with Solid Tumors Harboring NTRK Fusion, run by Bayer at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with adverse events (time frame: 25 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02122913, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2026.

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