A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001)

NCT03157128 | Active Not Recruiting Phase 1 Results FDA Drug

• 5 other identifiers: 17477J2G-OX-JZJALOXO-RET-170012017-000800-592023-507702-13-00
• Study Type: interventional
• Target: 857
• Locations: 16 countries
• Sites: 85

Brief Summary

This is an open-label, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of selpercatinib (also known as LOXO-292) administered orally to participants with advanced solid tumors, including rearranged during transfection (RET)-fusion-positive solid tumors, medullary thyroid cancer (MTC) and other tumors with RET activation.

Conditions

Medullary Thyroid Cancer; Colon Cancer; Any Solid Tumor; Non-Small Cell Lung Cancer

Keywords

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; RET-PTC9; ACBD5-RET; MYH13-RET; CUX1-RET; KIAA1468-RET; FRMD4A-RET; SQSTM1-RET; AFAP1L2-RET; PPFIBP2-RET; EML4-RET; PARD3-RET; G533C; C609F; C609G; C609R; C609S; C609Y; C611F; C611G; C611S; C611Y; C611W; C618F; C618R; C618S; C620F; C620R; C620S; C630R; C630Y; D631Y; C634F; C634G; C634R; C634S; C634W; C634Y; K666E; E768D; L790F; V804L; V804M; A883F; S891A; R912P; CLIP1-RET; Y806C; RET fusion; RET alteration; RET mutation; RET rearrangement; RET translocation; Neoplasms by Site; Neoplasms; Non-Small Cell Lung Cancer; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Cancer of Lung; Cancer of the Lung; Lung Cancer; Neoplasms, Lung; Neoplasms, Pulmonary; Pulmonary Cancer; Pulmonary Neoplasms; Respiratory Tract Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Medullary Thyroid Cancer; Papillary Thyroid Cancer; Thyroid Diseases; Thyroid Neoplasms; Cancer of the Thyroid; Cancer of Thyroid; Neoplasms, Thyroid; Thyroid Ademona; Thyroid Cancer; Thyroid Carcinoma; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thoracic Neoplasms; CNS tumor; Primary CNS tumor; Cancer of Colon; Cancer of the Colon; Colon Cancer; Colon Neoplasms; Colonic Cancer; Neoplasms, Colonic; Malignant tumor of Breast; Mammary Cancer; Mammary Carcinoma, Human; Mammary Neoplasm, Human; Neoplasms, Breast; Tumors, Breast; Human Mammary Carcinoma; Malignant Neoplasm of Breast; Breast Carcinoma; Breast Tumors; Cancer of the Breast; Breast Neoplasms; Breast Cancer; RET Inhibitor; MTC; NSCLC; selpercatinib; neo-adjuvant treatment in early stage NSCLC

Outcome Measures

Primary Outcomes (3)

• Phase 1: Maximum Tolerated Dose (MTD)

  The MTD is defined as the highest dose level at which none of the first 3 treated patients, or not more than 1 of the first 6 treated patients, experiences a DLT. A DLT is any adverse events that starts on or after first administration of study drug, as defined by National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. * Any Grade(G) ≥3 nonhematologic toxicity, excluding * G3 AST, ALT, and/or total bilirubin elevation for \<7 days. * G3 neutropenia \<7 days * G3 thrombocytopenia without clinically significant bleeding * G3 or G4 lymphopenia. * First occurrence of G3 or G4 electrolyte abnormalities * G3 fatigue, weakness, nausea; other manageable constitutional symptom * G3 or G4 vomiting or diarrhea that lasts for \<48hours with antiemetic/antidiarrheal medication in case of G3 and \<24 hours in case of G4 * G4 manageable constitutional symptom.

  Cycle 1 (cycle length = 28 days)

• Phase 1: Recommended Phase 2 Dose (RP2D)

  Phase 1: RP2D

  Cycle 1 (cycle length = 28 days)

• Phase 2: Objective Response Rate (ORR) Based on Independent Review Committee (IRC) Assessment

  Objective Response Rate was defined as the percentage of participants with best overall response of confirmed response (CR), or Partial response (PR). Response was confirmed by a repeat assessment no less than 28 days. * CR is defined as disappearance of all target lesions. * PR is defined as at least a 30% decrease in the sum of diameter (LD for non-nodal lesions and short axis diameter \[SAD\] for nodal lesions) of target lesions, taking as reference the baseline sum LD. ORR was assessed by independent review committee (IRC) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. 95% confidence interval was calculated using Clopper-Pearson method.

  Approximately for up to 7 years 8 months

Secondary Outcomes (17)

• Phase 1: Number of Participants With a Treatment-Related Adverse Event(s) (TRAE[s])

  Up to 28 days

• Phase 1: Number of Participants With an Abnormal Laboratory Values

  Up to 28 days

• Phase 2: Overall Response Rate (ORR) Based on RECIST 1.1 or RANO, as Appropriate to Tumor Type

  Approximately for up to 9 years 8 months

• Phase 2: ORR (by Investigator)

  Approximately for up to 9 years 8 months

• Phase 2: Best Change in Tumor Size From Baseline (by IRC and Investigator)

  Approximately for up to 9 years 8 months

Study Arms (16)

Phase 1: 20 mg Selpercatinib QD

EXPERIMENTAL

Participants received Selpercatinib 20 milligrams (mg) administered orally once daily (QD), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.

Drug: LOXO-292

Phase 1: 20 mg Selpercatinib BID

EXPERIMENTAL

Participants received Selpercatinib 20 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.

Drug: LOXO-292

Phase 1: 40 mg Selpercatinib BID

EXPERIMENTAL

Participants received Selpercatinib 40 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.

Drug: LOXO-292

Phase 1: 60 mg Selpercatinib BID

EXPERIMENTAL

Participants received Selpercatinib 60 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.

Drug: LOXO-292

Phase 1: 160 mg Selpercatinib QD

EXPERIMENTAL

Participants received Selpercatinib 160 milligrams (mg) administered orally once daily (QD), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.

Drug: LOXO-292

Phase 1: 80 mg Selpercatinib BID

EXPERIMENTAL

Participants received Selpercatinib 80 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.

Drug: LOXO-292

Phase 1: 120 mg Selpercatinib BID

EXPERIMENTAL

Participants received Selpercatinib 120 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.

Drug: LOXO-292

Phase 1: 160 mg Selpercatinib BID

EXPERIMENTAL

Participants received Selpercatinib 160 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.

Drug: LOXO-292

Phase 1: 200 mg Selpercatinib BID

EXPERIMENTAL

Participants received Selpercatinib 200 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.

Drug: LOXO-292

Phase 1: 240 mg Selpercatinib BID

EXPERIMENTAL

Participants received Selpercatinib 240 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.

Drug: LOXO-292

Phase 2, Cohort 1: RET Fusion Solid Tumor

EXPERIMENTAL

Participants with Rearranged during transfection (RET) Fusion solid tumor progressed on/intolerant to standard first line therapy received Selpercatinib 160 milligrams (mg) administered orally twice daily (BID), in a continuous 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.

Drug: LOXO-292

Phase 2, Cohort 2: RET Fusion Solid Tumor Without Standard Therapy

EXPERIMENTAL

Participants with RET Fusion solid tumor without standard first line therapy received Selpercatinib 160 milligrams (mg) administered orally twice daily (BID), in a continuous 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.

Drug: LOXO-292

Phase 2, Cohort 3: RET Mutant MTC

EXPERIMENTAL

Participants with RET mutant medullary thyroid cancer (MTC) progressed on/intolerant to standard first line therapy received Selpercatinib 160 milligrams (mg) administered orally twice daily (BID), in a continuous 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.

Drug: LOXO-292

Phase 2, Cohort 4: RET Mutant MTC Without Standard Therapy

EXPERIMENTAL

Participants with RET mutant MTC without prior standard first line therapy or other kinase inhibitor(s) with anti-RET activity received Selpercatinib 160 milligrams (mg) administered orally twice daily (BID), in a continuous 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.

Drug: LOXO-292

Phase 2, Cohort 5: Advanced RET Altered Solid Tumor

EXPERIMENTAL

Participants with RET altered solid tumor (cohorts 1-4, disease not measurable; MTC not eligible for Cohort 3 or 4; MTC syndrome spectrum cancer; circulating free tumor DNA \[cfDNA+\] for RET alteration not known to be present in tumor) received Selpercatinib 160 milligrams (mg) administered orally twice daily (BID), in a continuous 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.

Drug: LOXO-292

Phase 2, Cohort 6: RET Inhibitor-Discontinued Participants

EXPERIMENTAL

Participants otherwise eligible for Cohorts 1-5 who discontinued other RET inhibitors received Selpercatinib 160 milligrams (mg) administered orally twice daily (BID), in a continuous 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.

Drug: LOXO-292

Interventions

LOXO-292 DRUG

Oral LOXO-292

Also known as: Selpercatinib, LY3527723

Phase 1: 120 mg Selpercatinib BID; Phase 1: 160 mg Selpercatinib BID; Phase 1: 160 mg Selpercatinib QD; Phase 1: 20 mg Selpercatinib BID; Phase 1: 20 mg Selpercatinib QD; Phase 1: 200 mg Selpercatinib BID; Phase 1: 240 mg Selpercatinib BID; Phase 1: 40 mg Selpercatinib BID; Phase 1: 60 mg Selpercatinib BID; Phase 1: 80 mg Selpercatinib BID; Phase 2, Cohort 1: RET Fusion Solid Tumor; Phase 2, Cohort 2: RET Fusion Solid Tumor Without Standard Therapy; Phase 2, Cohort 3: RET Mutant MTC; Phase 2, Cohort 4: RET Mutant MTC Without Standard Therapy; Phase 2, Cohort 5: Advanced RET Altered Solid Tumor; Phase 2, Cohort 6: RET Inhibitor-Discontinued Participants

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Loxo Oncology, Inc.: collaborator

Study Sites (85)

Mayo Clinic of Scottsdale

Scottsdale, Arizona, 85259, United States

Location

City of Hope National Medical Center

Duarte, California, 91010-0269, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

Kaiser Permanente

Oakland, California, 94611-5400, United States

Location

Irvine Medical Center

Orange, California, 92868, United States

Location

University of California - San Diego

San Diego, California, 92103, United States

Location

UCSF Medical Center at Mission Bay

San Francisco, California, 94158, United States

Location

Kaiser Permanente Medical Center

Walnut Creek, California, 94596, United States

Location

Sarah Cannon Research Institute at HealthOne

Denver, Colorado, 80218, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

Location

Memorial Hospital Pembroke

Pembroke, Florida, 33028, United States

Location

Emory University

Atlanta, Georgia, 30329-5102, United States

Location

University of Chicago Medicine-Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905-0002, United States

Location

Washington University Medical School

St Louis, Missouri, 63110, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

NYU Langone

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University Hospital

Columbus, Ohio, 43210-1257, United States

Location

Oregon Health and Science University

Portland, Oregon, 97201, United States

Location

University of Pennsylvania Hospital

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Sarah Cannon Research Institute SCRI

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-6303, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75390-9063, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

USO-Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

University of Wisconsin-Madison Hospital and Health Clinic

Madison, Wisconsin, 53792, United States

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

BC Cancer Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Rigshospitalet

Copenhagen, 2200, Denmark

Location

Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest

Bordeaux, Aquitaine, 33076, France

Location

Centre Leon Berard

Lyon, Auvergne-Rhône-Alpes, 69008, France

Location

APHM Hôpital de la Timone

Marseille, 13385, France

Location

Institut du Cancer de Montpellier - Val d'aurelle

Montpellier, 34298, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Hôpital Européen Georges Pompidou

Paris, Île-de-France Region, 75015, France

Location

Universitätsklinikum Würzburg A. ö. R.

Würzburg, Bavaria, 97080, Germany

Location

Universitätsklinikum Köln

Cologne, North Rhine-Westphalia, 50931, Germany

Location

Prince of Wales Hospital

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

Location

Sheba Medical Center

Ramat Gan, Central District, 5262100, Israel

Location

Shaare Zedek Medical Center

Jerusalem, Jerusalem, 9103102, Israel

Location

Soroka Medical Center - Pediatric Outpatient Clinic

Beersheba, 8410101, Israel

Location

Hadassah Medical Center

Jerusalem, 9112001, Israel

Location

Istituto Nazionale dei Tumori

Milan, Lombardy, 20133, Italy

Location

Nagoya University Hospital

Nagoya, Aichi-ken, 466-8560, Japan

Location

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan

Location

Hyogo Cancer Center

Akashi, Hyōgo, 673-8558, Japan

Location

Kanazawa University Hospital

Kanazawa, Ishikawa-ken, 920-8641, Japan

Location

Kindai University Hospital

Osaka Sayama-shi, Osaka, 589 8511, Japan

Location

Tominaga Hospital

Nagaizumi-cho,Sunto-gun, Shizuoka, 411-8777, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Japanese Foundation for Cancer Research

Koto, Tokyo, 135-8550, Japan

Location

Tottori University Hospital

Yonago, Tottori, 683-8504, Japan

Location

National Hospital Organization Kyushu Cancer Center

Fukuoka, 811-1395, Japan

Location

Okayama University Hospital

Okayama, 700-8558, Japan

Location

Osaka City General Hospital

Osaka, 534-0021, Japan

Location

National Cancer Centre Singapore

Singapore, Central Singapore, 169610, Singapore

Location

National Cancer Center

Goyang-si, Kyǒnggi-do, 10408, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, Kyǒnggi-do, 13620, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, Seoul-teukbyeolsi [Seoul], 03722, South Korea

Location

Asan Medical Center

Seoul, Seoul-teukbyeolsi [Seoul], 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona [Barcelona], 8035, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Madrid Norte Sanchinarro

Madrid, 28050, Spain

Location

Kantonsspital Luzern

Lucerne, Canton of Lucerne, 6000, Switzerland

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

Related Publications (13)

• Gautschi O, Park K, Solomon BJ, Tomasini P, Loong HH, De Braud F, Goto K, Peterson P, Barker S, Liming K, Oxnard GR, Frimodt-Moller B, Drilon A. Selpercatinib in RET Fusion-Positive Non-Small Cell Lung Cancer: Final Safety and Efficacy, Including Overall Survival, From the LIBRETTO-001 Phase I/II Trial. J Clin Oncol. 2025 May 20;43(15):1758-1764. doi: 10.1200/JCO-24-02076. Epub 2025 Feb 21.

  PMID: 39983053 DERIVED

• Wirth LJ, Brose MS, Subbiah V, Worden F, Solomon B, Robinson B, Hadoux J, Tomasini P, Weiler D, Deschler-Baier B, Tan DSW, Maeda P, Lin Y, Singh R, Bayt T, Drilon A, Cassier PA. Durability of Response With Selpercatinib in Patients With RET-Activated Thyroid Cancer: Long-Term Safety and Efficacy From LIBRETTO-001. J Clin Oncol. 2024 Sep 20;42(27):3187-3195. doi: 10.1200/JCO.23.02503. Epub 2024 Aug 2.

  PMID: 39094065 DERIVED

• Deschler-Baier B, Krebs M, Kroiss M, Chatterjee M, Gundel D, Kestler C, Kerscher A, Kunzmann V, Appenzeller S, Maurus K, Rosenwald A, Bargou R, Gerhard-Hartmann E, Venkataramani V. Rapid response to selpercatinib in RET fusion positive pancreatic neuroendocrine carcinoma confirmed by smartwatch. NPJ Precis Oncol. 2024 Jul 31;8(1):167. doi: 10.1038/s41698-024-00659-x.

  PMID: 39085487 DERIVED

• Deschler-Baier B, Konda B, Massarelli E, Hu MI, Wirth LJ, Xu X, Wright J, Clifton-Bligh RJ. Clinical Activity of Selpercatinib in RET-mutant Pheochromocytoma. J Clin Endocrinol Metab. 2025 Feb 18;110(3):e600-e606. doi: 10.1210/clinem/dgae283.

  PMID: 38661071 DERIVED

• 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: 37934000 DERIVED

• Duke ES, Bradford D, Marcovitz M, Amatya AK, Mishra-Kalyani PS, Nguyen E, Price LSL, Fourie Zirkelbach J, Li Y, Bi Y, Kraft J, Dorff SE, Scepura B, Stephenson M, Ojofeitimi I, Nair A, Han Y, Tezak Z, Lemery SJ, Pazdur R, Larkins E, Singh H. FDA Approval Summary: Selpercatinib for the Treatment of Advanced RET Fusion-Positive Solid Tumors. Clin Cancer Res. 2023 Sep 15;29(18):3573-3578. doi: 10.1158/1078-0432.CCR-23-0459.

  PMID: 37265412 DERIVED

• Murciano-Goroff YR, Falcon CJ, Lin ST, Chacko C, Grimaldi G, Liu D, Wilhelm C, Iasonos A, Drilon A. Central Nervous System Disease in Patients With RET Fusion-Positive NSCLC Treated With Selpercatinib. J Thorac Oncol. 2023 May;18(5):620-627. doi: 10.1016/j.jtho.2023.01.008. Epub 2023 Jan 16.

  PMID: 36657661 DERIVED

• Drilon A, Subbiah V, Gautschi O, Tomasini P, de Braud F, Solomon BJ, Shao-Weng Tan D, Alonso G, Wolf J, Park K, Goto K, Soldatenkova V, Szymczak S, Barker SS, Puri T, Bence Lin A, Loong H, Besse B. Selpercatinib in Patients With RET Fusion-Positive Non-Small-Cell Lung Cancer: Updated Safety and Efficacy From the Registrational LIBRETTO-001 Phase I/II Trial. J Clin Oncol. 2023 Jan 10;41(2):385-394. doi: 10.1200/JCO.22.00393. Epub 2022 Sep 19.

  PMID: 36122315 DERIVED

• Subbiah V, Wolf J, Konda B, Kang H, Spira A, Weiss J, Takeda M, Ohe Y, Khan S, Ohashi K, Soldatenkova V, Szymczak S, Sullivan L, Wright J, Drilon A. Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial. Lancet Oncol. 2022 Oct;23(10):1261-1273. doi: 10.1016/S1470-2045(22)00541-1. Epub 2022 Sep 12.

  PMID: 36108661 DERIVED

• Rolfo C, Hess LM, Jen MH, Peterson P, Li X, Liu H, Lai Y, Sugihara T, Kiiskinen U, Vickers A, Summers Y. External control cohorts for the single-arm LIBRETTO-001 trial of selpercatinib in RET+ non-small-cell lung cancer. ESMO Open. 2022 Aug;7(4):100551. doi: 10.1016/j.esmoop.2022.100551. Epub 2022 Aug 2.

  PMID: 35930972 DERIVED

• Subbiah V, Gainor JF, Oxnard GR, Tan DSW, Owen DH, Cho BC, Loong HH, McCoach CE, Weiss J, Kim YJ, Bazhenova L, Park K, Daga H, Besse B, Gautschi O, Rolfo C, Zhu EY, Kherani JF, Huang X, Kang S, Drilon A. Intracranial Efficacy of Selpercatinib in RET Fusion-Positive Non-Small Cell Lung Cancers on the LIBRETTO-001 Trial. Clin Cancer Res. 2021 Aug 1;27(15):4160-4167. doi: 10.1158/1078-0432.CCR-21-0800. Epub 2021 Jun 4.

  PMID: 34088726 DERIVED

• Wirth LJ, Sherman E, Robinson B, Solomon B, Kang H, Lorch J, Worden F, Brose M, Patel J, Leboulleux S, Godbert Y, Barlesi F, Morris JC, Owonikoko TK, Tan DSW, Gautschi O, Weiss J, de la Fouchardiere C, Burkard ME, Laskin J, Taylor MH, Kroiss M, Medioni J, Goldman JW, Bauer TM, Levy B, Zhu VW, Lakhani N, Moreno V, Ebata K, Nguyen M, Heirich D, Zhu EY, Huang X, Yang L, Kherani J, Rothenberg SM, Drilon A, Subbiah V, Shah MH, Cabanillas ME. Efficacy of Selpercatinib in RET-Altered Thyroid Cancers. N Engl J Med. 2020 Aug 27;383(9):825-835. doi: 10.1056/NEJMoa2005651.

  PMID: 32846061 DERIVED

• Drilon A, Oxnard GR, Tan DSW, Loong HHF, Johnson M, Gainor J, McCoach CE, Gautschi O, Besse B, Cho BC, Peled N, Weiss J, Kim YJ, Ohe Y, Nishio M, Park K, Patel J, Seto T, Sakamoto T, Rosen E, Shah MH, Barlesi F, Cassier PA, Bazhenova L, De Braud F, Garralda E, Velcheti V, Satouchi M, Ohashi K, Pennell NA, Reckamp KL, Dy GK, Wolf J, Solomon B, Falchook G, Ebata K, Nguyen M, Nair B, Zhu EY, Yang L, Huang X, Olek E, Rothenberg SM, Goto K, Subbiah V. Efficacy of Selpercatinib in RET Fusion-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2020 Aug 27;383(9):813-824. doi: 10.1056/NEJMoa2005653.

  PMID: 32846060 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Carcinoma, Medullary; Colonic Neoplasms; Neoplasms by Site; Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Thyroid Cancer, Papillary; Thyroid Diseases; Thyroid Neoplasms; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thoracic Neoplasms; Central Nervous System Neoplasms; Breast Neoplasms

Interventions

selpercatinib

Condition Hierarchy (Ancestors)

Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms, Nerve Tissue; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Bronchial Diseases; Adenocarcinoma, Papillary; Nervous System Neoplasms; Nervous System Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

08005455979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: May 9, 2017
• First Posted: May 17, 2017
• Study Start: May 2, 2017
• Primary Completion: February 14, 2025
• Study Completion (Estimated): February 1, 2027
• Last Updated: April 16, 2026
• Results First Posted: April 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (41); TW (2); FR (6); SG (1); KR (5); IT (1); CH (1); CA (1); DE (2); GB (1); DK (1); ES (3); AU (2); HK (1); IL (4); JP (13)