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Phase 1/2 Study of LOXO-292 in Patients With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03157128
Recruitment Status : Recruiting
First Posted : May 17, 2017
Last Update Posted : September 13, 2019
Sponsor:
Information provided by (Responsible Party):
Loxo Oncology, Inc.

Brief Summary:
This is a Phase 1/2, open-label, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of LOXO-292 administered orally to patients with advanced solid tumors, including RET-fusion-positive solid tumors, medullary thyroid cancer (MTC) and other tumors with RET activation.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Medullary Thyroid Cancer Colon Cancer Any Solid Tumor Drug: LOXO-292 Phase 1 Phase 2

Detailed Description:
This is an open-label, multi-center Phase 1/2 study in patients with advanced solid tumors, including RET fusion-positive solid tumors, MTC, and other tumors with RET activation. The trial will be conducted in 2 parts: phase 1 (dose escalation) and phase 2 (dose expansion). Patients with advanced cancer are eligible if they have progressed on or are intolerant to available standard therapies, or no standard or available curative therapy exists, or in the opinion of the Investigator, they would be unlikely to tolerate or derive significant clinical benefit from appropriate standard of care therapy, or they declined standard therapy. A dose of 160 mg BID has been selected as the recommended phase 2 dose (RP2D). Up to ~850 patients with advanced solid tumors harboring a RET gene alteration in tumor and/or blood will be enrolled to one of five phase 2 cohorts.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 970 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of Oral LOXO-292 in Patients With Advanced Solid Tumors, Including RET Fusion-Positive Solid Tumors, Medullary Thyroid Cancer, and Other Tumors With RET Activation (LIBRETTO-001)
Actual Study Start Date : May 9, 2017
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : May 2022


Arm Intervention/treatment
Experimental: LOXO-292
Phase 1 - Multiple doses of LOXO-292 Phase 2 - The maximum tolerated dose (MTD)/recommended dose for Phase 2 (RP2D)
Drug: LOXO-292
Oral LOXO-292




Primary Outcome Measures :
  1. Phase 1: Maximum tolerated dose (MTD) [ Time Frame: The first 28 days of treatment (Cycle 1) ]
  2. Phase 1: Recommended Phase 2 dose (RP2D) [ 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) ]
  3. Phase 2: Objective Response Rate [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
    As assessed by RECIST v1.1 or RANO, as appropriate to tumor type, as assessed by independent review committee (IRC)


Secondary Outcome Measures :
  1. Phase 1: Frequency, severity, and relatedness of TEAEs and serious adverse events (SAEs), changes in hematology and blood chemistry values, assessments of physical examinations, vital signs, and electrocardiograms (ECGs). [ 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) ]
  2. Phase 1: Plasma concentration of LOXO-292 and PK parameters, including but not limited toarea under the curve from time 0 to 24 hours (AUC0-24), maximum drug concentration (Cmax), time to maximum plasma concentration (Tmax), and degree of accumulation. [ Time Frame: Day 8 of Cycle 1 and Day 8 after Intra-patient Dose Escalation (Phase 1 only) ]
  3. Phase 1: ORR based on RECIST 1.1 or RANO, as appropriate to tumor type. [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
  4. Phase 2: ORR (by Investigator) [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
  5. Phase 2: best change in tumor size from baseline (by IRC and Investigator) [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
  6. Phase 2: DOR (by IRC and Investigator) [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
  7. Phase 2: CNS ORR (by IRC) [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
  8. Phase 2: CNS DOR (by IRC) [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
  9. Phase 2: time to any and best response (by IRC and Investigator) [ Time Frame: every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
  10. Phase 2: CBR (by IRC and Investigator) [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
  11. Phase 2: PFS (by IRC and Investigator) [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
  12. Phase 2: OS [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
  13. Phase 2: Frequency, severity and relatedness of TEAEs and SAEs, changes in hematology and blood chemistry values, assessments of physical examinations, vital signs and ECGs. [ 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) ]
  14. Phase 2: Plasma concentrations of LOXO-292 and PK parameters, including but not limited to AUC0-24, Cmax, and Tmax. [ Time Frame: Day 8 of Cycle 1 and Day 8 after Intra-patient Dose Escalation (Phase 2 only) ]

Other Outcome Measures:
  1. Differences in efficacy and safety based on LOXO-292 PK parameters. [ Time Frame: Day 8 of Cycle 1 and Day 8 after Intra-patient Dose Escalation ]
  2. Changes in CEA and calcitonin (patients with MTC) thyroglobulin (non-MTC thyroid cancer patients), ACTH and cortisol (patients with Cushing's disease related to their cancer) with LOXO-292 treatment. [ Time Frame: From the time of informed consent, Day 1 and Day 15 of Cycle 1, then with each radiologic disease assessment, and 7 days after the last dose. ]
  3. Identity of RET gene fusions, mutations, and concurrently activated oncogenic pathways in tumor biopsies and cfDNA. [ Time Frame: Up to 28 days prior to C1D1, Day 1 & Day 15 of Cycle 1, Day 1 of Cycle 3, then approximately every 8 weeks for 1 year, then every 12 weeks, & 7 days after the last dose, for approximately 24 months (or earlier if the patient discontinues from the study) ]
  4. Changes from baseline in disease-related symptoms and HRQoL, as measured by EORTC QLQ-C30 (adults), PedsQL for teens (ages 13-17 years), and PedsQL for children (age 12 years). [ Time Frame: Day 1 of Cycle 1, then approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose, for approximately 24 months (or earlier if the patient discontinues from the study) ]
  5. Changes from baseline in disease-related symptoms and HRQoL, as measured by patient bowel diaries (MTC patients only). [ Time Frame: Day 1, Day 8, Day 15, and Day 22 of Cycle 1, and Day 1 of each cycle, and 7 days after the last dose, for approximately 24 months (or earlier if the patient discontinues from the study) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

For Phase 1

  • Patients with a locally advanced or metastatic solid tumor who:

    • have progressed on or are intolerant to standard therapy, or
    • no standard therapy exists, or in the opinion of the Investigator, are not candidates for or would be unlikely to tolerate or derive significant clinical benefit from standard therapy, or
    • decline standard therapy
  • Prior MKIs with anti-RET activity are allowed.
  • A RET gene alteration is not required initially. Once adequate PK exposure is achieved, evidence of RET gene alteration in tumor and/or blood is required as identified through molecular assays, as performed for clinical evaluation.
  • Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as appropriate to tumor type.
  • Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 or Lansky Performance Score (LPS) ≥ 40% (age < 16 years) with no sudden deterioration 2 weeks prior to the first dose of study treatment.
  • Adequate hematologic, hepatic and renal function.
  • Life expectancy of at least 3 months.

For Phase 2

As for phase 1 with the following modifications:

  • For Cohorts 1 and 3 Subjects must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy.
  • Cohorts 1-4: enrollment will be restricted to patients with evidence of a RET gene alteration in tumor. However, a positive germline DNA test for a RET gene mutation is acceptable in the absence of tumor tissue testing for patients with MTC.
  • Cohorts 1-4: at least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate to tumor type and not previously irradiated.
  • Cohort 4: radiographic PD within the previous 14 months.

Note: Patients otherwise eligible for cohort 4 who do not demonstrate radiographic PD within the previous 14 months may be enrolled to cohort 5 if a compelling rationale is provided by the investigator and approved by the Sponsor.

  • Cohort 5: (up to 150 patients):

    • Cohorts 1-4 without measurable disease;
    • MTC not meeting the requirements for Cohorts 3 or 4; (a known RET mutation is not required)
    • MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with neuroendocrine features/differentiation, or poorly differentiated thyroid cancers with other RET alteration/activation may be allowed with prior Sponsor approval;
    • cfDNA positive for a RET gene alteration not known to be present in a tumor sample.
  • Cohort 6: Patients who otherwise are eligible for Cohorts 1-5 who discontinued another RET inhibitor due to intolerance may be eligible with prior Sponsor approval.

Key Exclusion Criteria (Phase 1 and Phase 2):

  • Phase 2 Cohorts 1-4: an additional known oncogenic driver.
  • Cohorts 1-5: prior treatment with a selective RET inhibitor

Notes:

Patients otherwise eligible for Cohorts 1-5 who discontinued another selective RET inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval.

Notes:

Patients otherwise eligible for Cohorts 1-5 who discontinued another selective RET inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval.

Notes:

Patients otherwise eligible for Cohorts 1-5 who discontinued another selective RET inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval.

- Investigational agent or anticancer therapy (including chemotherapy, biologic therapy, immunotherapy, anticancer Chinese medicine or other anticancer herbal remedy) within 5 half-lives or 2 weeks (whichever is shorter) prior to planned start of LOXO-292. In addition, no concurrent investigational anti-cancer therapy is permitted.

Note:

Potential exception for this exclusion criterion will require a valid scientific justification and approval from the Sponsor.

  • Major surgery (excluding placement of vascular access) within 4 weeks prior to planned start of LOXO-292.
  • Radiotherapy with a limited field of radiation for palliation within 1 week of planned start of LOXO-292, with the exception of patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation, which must be completed at least 4 weeks prior to the first dose of study treatment.
  • Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy.
  • Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. Patients are eligible if neurological symptoms and CNS imaging are stable and steroid dose is stable for 14 days prior to the first dose of LOXO-292 and no CNS surgery or radiation has been performed for 28 days, 14 days if stereotactic radiosurgery [SRS].
  • Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292 or prolongation of the QT interval corrected (QTcF) > 470 msec.
  • Required treatment with certain strong CYP3A4 inhibitors or inducers and certain prohibited concomitant medications.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03157128


Contacts
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Contact: Patient Advocacy 855-RET-4-292 (855-738-4292) clinicaltrials@loxooncology.com

  Hide Study Locations
Locations
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United States, Arizona
Mayo Clinic - Scottsdale Recruiting
Scottsdale, Arizona, United States, 85259
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
UCSD Medical Center Recruiting
La Jolla, California, United States, 92093-0698
University of California, Los Angeles (UCLA) - Medical Center Recruiting
Los Angeles, California, United States, 90095
Hoag Memorial Hospital Presbyterian Recruiting
Newport Beach, California, United States, 92663
Kaiser Permanente of Oakland Recruiting
Oakland, California, United States, 94612
University of California - Irvine Medical Center Recruiting
Orange, California, United States, 92868
Kaiser Permanente- Sacramento Recruiting
Sacramento, California, United States, 95814
Kaiser Permanente - San Francisco Recruiting
San Francisco, California, United States, 94115
University of California, San Francisco (UCSF) - Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94115
Kaiser Permanente - Santa Clara, CA Recruiting
Santa Clara, California, United States, 95051
Kaiser Permanente- Vallejo Recruiting
Vallejo, California, United States, 94589
United States, Colorado
Sarah Cannon Research Institute at HealthONE Recruiting
Denver, Colorado, United States, 80218
United States, Connecticut
Yale University School of Medicine - Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06510
United States, Florida
Mayo Clinic - Jacksonville Recruiting
Jacksonville, Florida, United States, 32224
Memorial Hospital Recruiting
Pembroke Pines, Florida, United States, 33028
United States, Georgia
Emory University School of Medicine Recruiting
Atlanta, Georgia, United States, 30322
United States, Illinois
University of Chicago Medicine Recruiting
Chicago, Illinois, United States, 60637
United States, Louisiana
Ochsner Clinic Foundation Recruiting
New Orleans, Louisiana, United States, 70121
United States, Maryland
Johns Hopkins Kimmel Cancer Center Recruiting
Baltimore, Maryland, United States, 20016
University of Maryland Medical Center Recruiting
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Henry Ford Health System Recruiting
Detroit, Michigan, United States, 48202
South Texas Accelerated Research Therapeutics (START) Midwest Recruiting
Grand Rapids, Michigan, United States, 49503
United States, Minnesota
Mayo Clinic - Rochester Recruiting
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
United States, Nevada
Comprehensive Cancer Centers of Nevada Recruiting
Las Vegas, Nevada, United States, 89169
United States, New York
Roswell Park Comprehensive Cancer Center Recruiting
Buffalo, New York, United States, 14263
New York Cancer and Blood Specialists Recruiting
East Setauket, New York, United States, 11733
New York University (NYU) Langone Medical Center Recruiting
New York, New York, United States, 10016
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, North Carolina
University of North Carolina (UNC) - Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
The James Cancer Hospital and Solove Research Institute, The Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43221
United States, Oregon
Oregon Health & Science University (OHSU) Recruiting
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Sarah Cannon Research Institute, LLC Recruiting
Nashville, Tennessee, United States, 37203
Vanderbilt University School of Medicine Recruiting
Nashville, Tennessee, United States, 37232
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
United States, Utah
Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
United States, Wisconsin
University of Wisconsin - Carbone Cancer Center Recruiting
Madison, Wisconsin, United States, 53792
Australia
Peter MacCallum Cancer Institute Recruiting
Melbourne, Australia, 3000
Royal North Shore Hospital Recruiting
Saint Leonards, Australia, NSW 2065
Canada, British Columbia
British Columbia Cancer Agency Recruiting
Vancouver, British Columbia, Canada, VSZ 4E6
Denmark
The Finsen Centre Recruiting
Copenhagen, Denmark, 2100
France
Institut Bergonie Recruiting
Bordeaux, France, 33076
Centre Leon Berard Recruiting
Lyon, France, 69008
Hospital La Timone Recruiting
Marseille, France, 13005
ICM - Institut Regional du Cancer de Montpellier Recruiting
Montpellier, France, 34298
Hopital Europeen Georges Pompidou Recruiting
Paris, France, 75015
Gustave Roussy Recruiting
Villejuif, France, 94805
Germany
Uniklinik Koeln Recruiting
Koeln, Germany, 50937
Universitatsklinikum Wurzburg - Department of Internal Medicine I Recruiting
Würzburg, Germany, D-97080
Hong Kong
Prince of Wales Hospital - Department of Clinical Oncology Recruiting
Shatin, Hong Kong
Israel
Soroka University Medical Center - Dept. of Oncology Recruiting
Be'er Sheva, Israel, 8410101
Hadassah Hebrew University Medical Center Ein Karem Recruiting
Jerusalem, Israel, 9112001
Sheba Medical Center Recruiting
Tel HaShomer, Israel, 5265601
Italy
Istituto Nazionale Tumori - National Cancer Institute Recruiting
Milano, Italy, 20133
Japan
National Cancer Center Hospital East Recruiting
Kashiwa, Chiba, Japan, 277-8577
Hyogo Cancer Center Recruiting
Akashi, Japan, 673-8558
National Hospital Organization Kyushu Cancer Center Recruiting
Fukuoka, Japan
Hokkaido University Hospital Recruiting
Hokkaido, Japan, 060-8648
Kanazawa University Hospital Recruiting
Kanazawa City, Japan, 920-8641
Nagoya University Hospital Recruiting
Nagoya, Japan, 466-8560
Okayama University Hospital Recruiting
Okayama, Japan, 700-8558
Osaka City General Hospital Recruiting
Osaka, Japan, 5340021
Shizuoka Cancer Center Recruiting
Shizuoka, Japan, 411-8777
National Cancer Center Hospital Recruiting
Tokyo, Japan, 104-0045
Cancer Institute Hospital of JFCR Recruiting
Tokyo, Japan, 135-8550
Tottori University Hospital Recruiting
Tottori, Japan, 683-8504
Kindai University Hospital, Faculty of Medicine Recruiting
Ōsaka-sayama, Japan, 589-8511
Korea, Republic of
National Cancer Center Recruiting
Goyang-si, Korea, Republic of, 10408
Seoul National University Bundang Hospital Recruiting
Gyeonggi-do, Korea, Republic of, 13620
Severance Hospital, Yonsei University Health System Recruiting
Seoul, Korea, Republic of, 03722
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 05505
Samsung Medical Center Recruiting
Seoul, Korea, Republic of, 06351
Singapore
National Cancer Centre Recruiting
Singapore, Singapore, 169610
Spain
Hospital Universitario Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Fundacion Jimenez Diaz, START-Madrid Recruiting
Madrid, Spain, 28040
START Madrid, Hospital Universitario HM Sanchinarro Recruiting
Madrid, Spain, 28050
Switzerland
Luzerner General Hospital Recruiting
Luzern, Switzerland, 6000
Taiwan
Taichung Veterans General Hospital Recruiting
Taichung, Taiwan, 40705
National Taiwan University Hospital Recruiting
Taipei City, Taiwan, 10002 R.O.C
United Kingdom
Royal Marsden Hospital - Surrey Recruiting
Surrey, United Kingdom, SM2 5PT
Sponsors and Collaborators
Loxo Oncology, Inc.
Investigators
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Study Director: S. Michael Rothenberg, MD, PhD Loxo Oncology Medical Monitor, VP of R&D

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Responsible Party: Loxo Oncology, Inc.
ClinicalTrials.gov Identifier: NCT03157128     History of Changes
Other Study ID Numbers: LOXO-RET-17001
2017-000800-59 ( EudraCT Number )
First Posted: May 17, 2017    Key Record Dates
Last Update Posted: September 13, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Loxo Oncology, Inc.:
LOXO-292
KIF5B-RET
M918T
CCDC6-RET
RET-PTC1
NCOA4-RET
RET-PTC
RET-PTC3
RET-PTC4
PRKAR1A-RET
RET-PTC2
GOLGA5-RET
RET-PTC5
ERC1-RET
KTN1-RET
RET-PTC8
HOOK3-RET
PCM1-RET
TRIM24-RET
RET-PTC6
TRIM27-RET
TRIM33-RET
RET-PTC7
AKAP13-RET
FKBP15-RET
SPECC1L-RET
TBL1XR1-RET
BCR-RET
FGRF1OP-RET
RFG8-RET
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Colonic Neoplasms
Thyroid Neoplasms
Carcinoma, Neuroendocrine
Thyroid Diseases
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Endocrine System Diseases
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Endocrine Gland Neoplasms
Head and Neck Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Adenocarcinoma