New pill shows promise against Hard-to-Treat RET-Driven cancers

NCT ID NCT03157128

Disease control Sponsor: Eli Lilly and Company Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Jun 27, 2026

Summary

This study tests an oral drug called selpercatinib in people with advanced solid tumors that have RET gene alterations, including certain lung, thyroid, and colon cancers. The goal is to find the best dose and see if the drug can shrink tumors. About 857 participants are enrolled in this early-phase trial.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: Selpercatinib (LOXO-292), an oral targeted therapy
What this could lead to: If successful, this could provide a new treatment option for people with advanced cancers driven by RET gene changes, potentially shrinking tumors and delaying progression.
What could go wrong: This is an early-phase trial, so the drug may not work for everyone and could cause side effects. Results may not apply to all cancer types or stages.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 1/2

Runs two stages together: safety and dose first, then whether the treatment works.

Participants

857 people

The number who actually took part.

Started

May 2017

Expected to finish

Feb 2027

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

12 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Key Inclusion Criteria: For Phase 1: * Participants with a locally advanced or metastatic solid tumor that: * Has progressed on or is intolerant to standard therapy, or * For which 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 multikinase inhibitors (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) greater than or equal to (≥) 40 percent (%) (age less than \[\<\] 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 Cohort 1: Participants 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 and 2: * Enrollment will be restricted to participants with evidence of a RET gene alteration in tumor * At least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate to tumor type and not previously irradiated * Cohorts 3 and 4: Enrollment closed * Cohort 5: * Cohorts 1-4 without measurable disease * MCT not meeting the requirements for Cohorts 3 or 4 * 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: Participants who otherwise are eligible for Cohorts 1, 2 or 5 who discontinued another RET inhibitor may be eligible with prior Sponsor approval * Cohort 7: Participants with a histologically confirmed stage IB-IIIA NSCLC and a RET fusion; determined to be medically operable and tumor deemed resectable by a thoracic surgical oncologist, without prior systemic treatment for NSCLC Key Exclusion Criteria (Phase 1 and Phase 2): * Phase 2 Cohorts 1 and 2: an additional known oncogenic driver * Cohorts 3 and 4: Enrollment closed * Cohorts 1, 2 and 5: prior treatment with a selective RET inhibitor Notes: Participants otherwise eligible for Cohorts 1, 2, and 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 (selpercatinib). 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 2 weeks prior to planned start of LOXO-292 (selpercatinib) * Radiotherapy with a limited field of radiation for palliation within 1 week of planned start of LOXO-292 (selpercatinib), with the exception of participants 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 Common Terminology Criteria for Adverse Events (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. Participants 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 (selpercatinib) 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 (selpercatinib) or prolongation of the QT interval corrected (QTcF) greater than (\>) 470 milliseconds (msec) * Participants with implanted pacemakers may enter the study without meeting QTc criteria due to nonevaluable measurement if it is possible to monitor for QT changes. * Participants with bundle branch block may be considered for study entry if QTc is appropriate by a formula other than Fridericia's and if it is possible to monitor for QT changes. * Required treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and certain prohibited concomitant medications * Phase 2 Cohort 7 (neoadjuvant treatment): Participant must not have received prior systemic therapy for NSCLC.

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Conditions

The condition(s) this trial relates to.

breast neoplasm bronchial neoplasm bronchogenic carcinoma Carcinoma, Medullary central nervous system cancer colon carcinoma colonic neoplasm endocrine system disorder Head and Neck Neoplasms lung disorder lung neoplasm malignant endocrine neoplasm medullary thyroid gland carcinoma neoplasm Neoplasms by Site non-small cell lung carcinoma respiratory system disorder respiratory tract neoplasm RET fusion positive cancer Thoracic Neoplasms Thyroid Cancer, Papillary thyroid gland disorder Thyroid Neoplasms

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Any solid tumor Colon cancer Medullary thyroid cancer Non-small cell lung cancer

Contacts and locations

Locations

APHM Hôpital de la Timone

Marseille, 13385, France
Asan Medical Center

Seoul, Seoul-teukbyeolsi [Seoul], 05505, South Korea
BC Cancer Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada
Centre Leon Berard

Lyon, Auvergne-Rhône-Alpes, 69008, France
City of Hope National Medical Center

Duarte, California, 91010-0269, United States
Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States
Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States
Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States
Emory University

Atlanta, Georgia, 30329-5102, United States
Gustave Roussy

Villejuif, 94805, France
Hadassah Medical Center

Jerusalem, 9112001, Israel
Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States
Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan
Hospital Madrid Norte Sanchinarro

Madrid, 28050, Spain
Hospital Universitari Vall d'Hebron

Barcelona, Barcelona [Barcelona], 8035, Spain
Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain
Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States
Hyogo Cancer Center

Akashi, Hyōgo, 673-8558, Japan
Hôpital Européen Georges Pompidou

Paris, Île-de-France Region, 75015, France
Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest

Bordeaux, Aquitaine, 33076, France
Institut du Cancer de Montpellier - Val d'aurelle

Montpellier, 34298, France
Irvine Medical Center

Orange, California, 92868, United States
Istituto Nazionale dei Tumori

Milan, Lombardy, 20133, Italy
Japanese Foundation for Cancer Research

Koto, Tokyo, 135-8550, Japan
Johns Hopkins University

Baltimore, Maryland, 21287, United States
Kaiser Permanente

Oakland, California, 94611-5400, United States
Kaiser Permanente Medical Center

Walnut Creek, California, 94596, United States
Kanazawa University Hospital

Kanazawa, Ishikawa-ken, 920-8641, Japan
Kantonsspital Luzern

Lucerne, Canton of Lucerne, 6000, Switzerland
Kindai University Hospital

Osaka Sayama-shi, Osaka, 589 8511, Japan
Massachusetts General Hospital

Boston, Massachusetts, 02114, United States
Mayo Clinic

Rochester, Minnesota, 55905-0002, United States
Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States
Mayo Clinic of Scottsdale

Scottsdale, Arizona, 85259, United States
Memorial Hospital Pembroke

Pembroke, Florida, 33028, United States
Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States
NYU Langone

New York, New York, 10016, United States
Nagoya University Hospital

Nagoya, Aichi-ken, 466-8560, Japan
National Cancer Center

Goyang-si, Kyǒnggi-do, 10408, South Korea
National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan
National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan
National Cancer Centre Singapore

Singapore, Central Singapore, 169610, Singapore
National Hospital Organization Kyushu Cancer Center

Fukuoka, 811-1395, Japan
National Taiwan University Hospital

Taipei, 10002, Taiwan
Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States
Ohio State University Hospital

Columbus, Ohio, 43210-1257, United States
Okayama University Hospital

Okayama, 700-8558, Japan
Oregon Health and Science University

Portland, Oregon, 97201, United States
Osaka City General Hospital

Osaka, 534-0021, Japan
Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia
Prince of Wales Hospital

Hong Kong, Shatin, New Territories, 999077, Hong Kong
Rigshospitalet

Copenhagen, 2200, Denmark
Roswell Park Cancer Institute

Buffalo, New York, 14263, United States
Royal Marsden Hospital

London, SW3 6JJ, United Kingdom
Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia
START Midwest

Grand Rapids, Michigan, 49546, United States
Samsung Medical Center

Seoul, 06351, South Korea
Sarah Cannon Research Institute SCRI

Nashville, Tennessee, 37203, United States
Sarah Cannon Research Institute at HealthOne

Denver, Colorado, 80218, United States
Seoul National University Bundang Hospital

Seongnam, Kyǒnggi-do, 13620, South Korea
Severance Hospital, Yonsei University Health System

Seoul, Seoul-teukbyeolsi [Seoul], 03722, South Korea
Shaare Zedek Medical Center

Jerusalem, Jerusalem, 9103102, Israel
Sheba Medical Center

Ramat Gan, Central District, 5262100, Israel
Soroka Medical Center - Pediatric Outpatient Clinic

Beersheba, 8410101, Israel
Taichung Veterans General Hospital

Taichung, 40705, Taiwan
Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States
Tominaga Hospital

Nagaizumi-cho,Sunto-gun, Shizuoka, 411-8777, Japan
Tottori University Hospital

Yonago, Tottori, 683-8504, Japan
UCLA Medical Center

Los Angeles, California, 90095, United States
UCSF Medical Center at Mission Bay

San Francisco, California, 94158, United States
USO-Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States
University of California - San Diego

San Diego, California, 92103, United States
University of Chicago Medicine-Comprehensive Cancer Center

Chicago, Illinois, 60637, United States
University of Maryland Medical Center

Baltimore, Maryland, 21201, United States
University of Michigan

Ann Arbor, Michigan, 48109, United States
University of North Carolina

Chapel Hill, North Carolina, 27514, United States
University of Pennsylvania Hospital

Philadelphia, Pennsylvania, 19104, United States
University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States
University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75390-9063, United States
University of Wisconsin-Madison Hospital and Health Clinic

Madison, Wisconsin, 53792, United States
Universitätsklinikum Köln

Cologne, North Rhine-Westphalia, 50931, Germany
Universitätsklinikum Würzburg A. ö. R.

Würzburg, Bavaria, 97080, Germany
Vanderbilt University Medical Center

Nashville, Tennessee, 37232-6303, United States
Washington University Medical School

St Louis, Missouri, 63110, United States
Yale Cancer Center

New Haven, Connecticut, 06520, United States

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