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

NCT03157128 — Phase 1 / Phase 2, Active not recruiting, 857 participants, Eli Lilly and Company

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A Phase 1/2 Study of Oral Selpercatinib (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)

Registry	NCT03157128, acronym LIBRETTO-001
Status	Active not recruiting
Phase	Phase 1 / Phase 2
Study type	Interventional; na, single group, masking: none, treatment
Enrollment	857 (Actual)
Sponsor	Eli Lilly and Company (Industry); collaborators: Loxo Oncology, Inc.
Conditions	Non-Small Cell Lung Cancer, Medullary Thyroid Cancer, Colon Cancer, Any Solid Tumor
Interventions	LOXO-292 (Drug)
Dates	start 2017-05-02, primary completion 2025-02-14, completion 2027-02-01 (estimated), first posted 2017-05-17, last updated 2026-04-16
Locations	85 sites in United States, Australia, Canada, Denmark, France, Germany, Hong Kong, Israel and 8 more countries

-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.

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+Detailed description

This is an open-label, multi-center Phase 1/2 study in participants 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 - completed) and phase 2 (dose expansion). Participants 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 milligrams (mg) twice a day (BID) has been selected as the recommended phase 2 dose (RP2D). Approximately 875 participants with advanced solid tumors harboring a RET gene alteration in tumor and/or blood will be enrolled to one of six phase 2 cohorts:

* Cohort 1: Advanced RET fusion positive solid tumor other than NSCLC or thyroid cancer for participants who progressed on or intolerant to first line therapy (open)
* Cohort 2: Advanced RET fusion positive solid tumor other than NSCLC or thyroid cancer for treatment naïve participants (open)
* Cohort 3: Advanced RET-mutant MTC participants who progressed on or intolerant to first line therapy (closed)
* Cohort 4: Advanced RET-mutant MTC participants who are treatment naïve (closed)
* Cohort 5: Advanced RET-altered solid tumor for participants other than NSCLC or thyroid cancer and RET-mutant MEN2 spectrum tumors (e.g. pheochromocytoma) otherwise ineligible for cohorts 1-4. See details in inclusion/exclusion criteria (open)
* Cohort 6: Participants otherwise eligible for Cohorts 1-5 who discontinued another RET inhibitor due to intolerance may be eligible with prior Sponsor approval (closed)

+Arms and interventions

Arm	Type	Interventions	Description
Phase 1: 20 mg Selpercatinib QD	Experimental	Drug: LOXO-292	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.
Phase 1: 20 mg Selpercatinib BID	Experimental	Drug: LOXO-292	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.
Phase 1: 40 mg Selpercatinib BID	Experimental	Drug: LOXO-292	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.
Phase 1: 60 mg Selpercatinib BID	Experimental	Drug: LOXO-292	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.
Phase 1: 160 mg Selpercatinib QD	Experimental	Drug: LOXO-292	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.
Phase 1: 80 mg Selpercatinib BID	Experimental	Drug: LOXO-292	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.
Phase 1: 120 mg Selpercatinib BID	Experimental	Drug: LOXO-292	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.
Phase 1: 160 mg Selpercatinib BID	Experimental	Drug: LOXO-292	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.
Phase 1: 200 mg Selpercatinib BID	Experimental	Drug: LOXO-292	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.
Phase 1: 240 mg Selpercatinib BID	Experimental	Drug: LOXO-292	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.
Phase 2, Cohort 1: RET Fusion Solid Tumor	Experimental	Drug: LOXO-292	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.
Phase 2, Cohort 2: RET Fusion Solid Tumor Without Standard Therapy	Experimental	Drug: LOXO-292	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.
Phase 2, Cohort 3: RET Mutant MTC	Experimental	Drug: LOXO-292	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.
Phase 2, Cohort 4: RET Mutant MTC Without Standard Therapy	Experimental	Drug: LOXO-292	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.
Phase 2, Cohort 5: Advanced RET Altered Solid Tumor	Experimental	Drug: LOXO-292	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.
Phase 2, Cohort 6: RET Inhibitor-Discontinued Participants	Experimental	Drug: LOXO-292	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.

LOXO-292 (Drug), also known as Selpercatinib, LY3527723: Oral LOXO-292

+Outcome measures

Primary outcomes

Phase 1: Maximum Tolerated Dose (MTD) [Cycle 1 (cycle length = 28 days)]: 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.
Phase 1: Recommended Phase 2 Dose (RP2D) [Cycle 1 (cycle length = 28 days)]: Phase 1: RP2D
Phase 2: Objective Response Rate (ORR) Based on Independent Review Committee (IRC) Assessment [Approximately for up to 7 years 8 months]: 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.

Secondary outcomes

Phase 1: Number of Participants With a Treatment-Related Adverse Event(s) (TRAE[s]) [Up to 28 days]: Phase 1: Number of Participants with a TRAE(s) is reported.
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 based on RECIST 1.1 or RANO, as Appropriate to Tumor Type
Phase 2: ORR (by Investigator) [Approximately for up to 9 years 8 months]: Phase 2: ORR (by Investigator)
Phase 2: Best Change in Tumor Size From Baseline (by IRC and Investigator) [Approximately for up to 9 years 8 months]: Phase 2: Best Change in Tumor Size from Baseline (by IRC and Investigator)
Phase 2: Duration of Response (DOR; by IRC and Investigator) [Approximately for up to 9 years 8 months]: Phase 2: DOR (by IRC and Investigator)
Phase 2: Central Nervous System (CNS) ORR (by IRC) [Approximately for up to 9 years 8 months]: Phase 2: CNS ORR (by IRC)
Phase 2: CNS DOR (by IRC) [Approximately for up to 9 years 8 months]: Phase 2: CNS DOR (by IRC)
Phase 2: Time to Any and Best Response (by IRC and Investigator) [Approximately for up to 9 years 8 months]: Phase 2: Time to Any and Best Response (by IRC and Investigator)
Phase 2: CBR (by IRC and Investigator) [Approximately for up to 9 years 8 months]: Phase 2: CBR (by IRC and Investigator)
Phase 2: PFS (by IRC and Investigator) [Approximately for up to 9 years 8 months]: Phase 2: PFS (by IRC and Investigator)
Phase 2: Overall Survival (OS) [Approximately for up to 9 years 8 months]: Phase 2: OS
Phase 2: Percentage of Participants With Any Serious Adverse Event (SAE[s]) [Approximately for up to 9 years 8 months]: Phase 2: Percentage of Participants with any SAE(s)
Phase 2: Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve of LOXO-292 (Selpercatinib) [Cycle 5 Day 1 (Cycle = 28 days)]: Phase 2: PK: AUC of LOXO-292 (Selpercatinib)
Phase 2: PK: Maximum Concentration (Cmax) of LOXO-292 (Selpercatinib) [Cycle 5 Day 1 (Cycle = 28 days)]: Phase 2: PK: Cmax of LOXO-292 (Selpercatinib)
Phase 1: Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours [Cycle 1 Day 8: Predose, 1, 2, 4, 8, 24 hours post dose (cycle length = 28 days)]
Phase 1: Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) [Cycle 1 Day 8: Predose, 1, 2, 4, 8, 24 hours post dose (cycle length = 28 days)]

+Eligibility

Sex: All, ages: 12 Years to any

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.

+Locations (85)

Facility	City	Country
Mayo Clinic of Scottsdale	Scottsdale, Arizona	United States
City of Hope National Medical Center	Duarte, California	United States
UCLA Medical Center	Los Angeles, California	United States
Hoag Memorial Hospital Presbyterian	Newport Beach, California	United States
Kaiser Permanente	Oakland, California	United States
Irvine Medical Center	Orange, California	United States
University of California - San Diego	San Diego, California	United States
UCSF Medical Center at Mission Bay	San Francisco, California	United States
Kaiser Permanente Medical Center	Walnut Creek, California	United States
Sarah Cannon Research Institute at HealthOne	Denver, Colorado	United States
Yale Cancer Center	New Haven, Connecticut	United States
Mayo Clinic in Florida	Jacksonville, Florida	United States
Memorial Hospital Pembroke	Pembroke, Florida	United States
Emory University	Atlanta, Georgia	United States
University of Chicago Medicine-Comprehensive Cancer Center	Chicago, Illinois	United States
Ochsner Clinic Foundation	New Orleans, Louisiana	United States
University of Maryland Medical Center	Baltimore, Maryland	United States
Johns Hopkins University	Baltimore, Maryland	United States
Massachusetts General Hospital	Boston, Massachusetts	United States
Dana-Farber Cancer Institute	Boston, Massachusetts	United States
University of Michigan	Ann Arbor, Michigan	United States
START Midwest	Grand Rapids, Michigan	United States
Mayo Clinic	Rochester, Minnesota	United States
Washington University Medical School	St Louis, Missouri	United States
Comprehensive Cancer Centers of Nevada	Las Vegas, Nevada	United States
Roswell Park Cancer Institute	Buffalo, New York	United States
NYU Langone	New York, New York	United States
Memorial Sloan Kettering Cancer Center	New York, New York	United States
University of North Carolina	Chapel Hill, North Carolina	United States
Cleveland Clinic Foundation	Cleveland, Ohio	United States
Ohio State University Hospital	Columbus, Ohio	United States
Oregon Health and Science University	Portland, Oregon	United States
University of Pennsylvania Hospital	Philadelphia, Pennsylvania	United States
Thomas Jefferson University	Philadelphia, Pennsylvania	United States
Sarah Cannon Research Institute SCRI	Nashville, Tennessee	United States
Vanderbilt University Medical Center	Nashville, Tennessee	United States
University of Texas Southwestern Medical Center at Dallas	Dallas, Texas	United States
University of Texas MD Anderson Cancer Center	Houston, Texas	United States
Huntsman Cancer Institute	Salt Lake City, Utah	United States
USO-Virginia Cancer Specialists, PC	Fairfax, Virginia	United States
University of Wisconsin-Madison Hospital and Health Clinic	Madison, Wisconsin	United States
Royal North Shore Hospital	St Leonards, New South Wales	Australia
Peter MacCallum Cancer Centre	Melbourne, Victoria	Australia
BC Cancer Vancouver	Vancouver, British Columbia	Canada
Rigshospitalet	Copenhagen	Denmark
Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest	Bordeaux, Aquitaine	France
Centre Leon Berard	Lyon, Auvergne-Rhône-Alpes	France
APHM Hôpital de la Timone	Marseille	France
Institut du Cancer de Montpellier - Val d'aurelle	Montpellier	France
Gustave Roussy	Villejuif	France
Hôpital Européen Georges Pompidou	Paris, Île-de-France Region	France
Universitätsklinikum Würzburg A. ö. R.	Würzburg, Bavaria	Germany
Universitätsklinikum Köln	Cologne, North Rhine-Westphalia	Germany
Prince of Wales Hospital	Hong Kong, Shatin, New Territories	Hong Kong
Sheba Medical Center	Ramat Gan, Central District	Israel
Shaare Zedek Medical Center	Jerusalem, Jerusalem	Israel
Soroka Medical Center - Pediatric Outpatient Clinic	Beersheba	Israel
Hadassah Medical Center	Jerusalem	Israel
Istituto Nazionale dei Tumori	Milan, Lombardy	Italy
Nagoya University Hospital	Nagoya, Aichi-ken	Japan
National Cancer Center Hospital East	Kashiwa, Chiba	Japan
Hokkaido University Hospital	Sapporo, Hokkaido	Japan
Hyogo Cancer Center	Akashi, Hyōgo	Japan
Kanazawa University Hospital	Kanazawa, Ishikawa-ken	Japan
Kindai University Hospital	Osaka Sayama-shi, Osaka	Japan
Tominaga Hospital	Nagaizumi-cho,Sunto-gun, Shizuoka	Japan
National Cancer Center Hospital	Chuo-ku, Tokyo	Japan
Japanese Foundation for Cancer Research	Koto, Tokyo	Japan
Tottori University Hospital	Yonago, Tottori	Japan
National Hospital Organization Kyushu Cancer Center	Fukuoka	Japan
Okayama University Hospital	Okayama	Japan
Osaka City General Hospital	Osaka	Japan
National Cancer Centre Singapore	Singapore, Central Singapore	Singapore
National Cancer Center	Goyang-si, Kyǒnggi-do	South Korea
Seoul National University Bundang Hospital	Seongnam, Kyǒnggi-do	South Korea
Severance Hospital, Yonsei University Health System	Seoul, Seoul-teukbyeolsi [Seoul]	South Korea
Asan Medical Center	Seoul, Seoul-teukbyeolsi [Seoul]	South Korea
Samsung Medical Center	Seoul	South Korea
Hospital Universitari Vall d'Hebron	Barcelona, Barcelona [Barcelona]	Spain
Hospital Universitario Fundación Jiménez Díaz	Madrid	Spain
Hospital Madrid Norte Sanchinarro	Madrid	Spain
Kantonsspital Luzern	Lucerne, Canton of Lucerne	Switzerland
Taichung Veterans General Hospital	Taichung	Taiwan
National Taiwan University Hospital	Taipei	Taiwan
Royal Marsden Hospital	London	United Kingdom

+Publications

Results publication: 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
Results publication: Raez LE, Massey AC, Barker SS, Peterson PM, Liming K, Pennell NA. Long-term safety of selpercatinib for Rearranged during transfection (RET)-activated advanced solid tumors in LIBRETTO-001: differing patterns of adverse events over time. Oncologist. 2024 Dec 6;29(12):1068-1078. doi: 10.1093/oncolo/oyae282. PMID 39471424
Results publication: 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
Results publication: 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
Results publication: 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
Results publication: 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
Results publication: 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
Results publication: 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
Results publication: 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
Results publication: 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
Results publication: 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
Results publication: 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
Results publication: 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
Results publication: 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

+Study documents

Study Protocol (PDF, 2023-08-15)
Statistical Analysis Plan (PDF, 2022-12-19)

+Investigators

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), Study director, Eli Lilly and Company

+Funding

NIH grants: 2023, 2017

My Notes

Public

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