Breast Cancer Clinical Trial

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

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.

View Full Description

Full 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 seven 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)
Cohort 7: RET fusion positive early-stage non-small cell lung cancer (NSCLC) participants who are candidates for definitive surgery. Participants will receive selpercatinib in a neoadjuvant and adjuvant setting. Participants will be followed for disease recurrence for up to 5 years from the date of surgery (closed)

View Eligibility Criteria

Eligibility Criteria

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.

Study is for people with:

Breast Cancer

Phase:

Phase 1

Estimated Enrollment:

875

Study ID:

NCT03157128

Recruitment Status:

Recruiting

Sponsor:

Loxo Oncology, Inc.

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There are 84 Locations for this study

See Locations Near You

Mayo Clinic of Scottsdale
Scottsdale Arizona, 85259, United States More Info
Contact
480-301-8000
Nina J Karlin
Principal Investigator
City of Hope National Medical Center
Duarte California, 91010, United States More Info
Contact
818-359-8111
Erminia Massarelli
Principal Investigator
University of California - San Diego
La Jolla California, 92161, United States More Info
Contact
858-822-6189
Lyudmila Bazhenova
Principal Investigator
UCLA Medical Center
Los Angeles California, 90095, United States More Info
Contact
310-794-1816
Jonathan W Goldman
Principal Investigator
Hoag Memorial Hospital Presbyterian
Newport Beach California, 92663, United States More Info
Contact
949-761-6767
Michael Demeure
Principal Investigator
Irvine Medical Center
Orange California, 92868, United States More Info
Contact
714-456-8105
Misako Nagasaka
Principal Investigator
UCSF Medical Center at Mission Bay
San Francisco California, 94115, United States More Info
Contact
415-885-3882
Hyunseok Kang
Principal Investigator
Kaiser Permanente
Santa Clara California, 95051, United States More Info
Contact
708-851-9588
Minggui Pan
Principal Investigator
Kaiser Permanente Medical Center
Vallejo California, 94589, United States More Info
Contact
5108913414
Jennifer Marie Suga
Principal Investigator
Sarah Cannon Research Institute at HealthOne
Denver Colorado, 80218, United States More Info
Contact
720-754-2610
Gerald S Falchook
Principal Investigator
Yale Cancer Center
New Haven Connecticut, 06510, United States More Info
Contact
203-737-5234
Frederick H Wilson
Principal Investigator
Johns Hopkins University
Washington District of Columbia, 20016, United States More Info
Contact
202-660-6500
Benjamin Levy
Principal Investigator
Mayo Clinic in Florida
Jacksonville Florida, 32224, United States More Info
Contact
904-953-2224
Victor Bernet
Principal Investigator
Memorial Hospital Pembroke
Pembroke Florida, 33028, United States More Info
Contact
954-265-4325
Luis Raez
Principal Investigator
Emory University
Atlanta Georgia, 30322, United States More Info
Contact
404-778-5378
Conor Steuer
Principal Investigator
University of Chicago Medicine-Comprehensive Cancer Center
Chicago Illinois, 60637, United States More Info
Christine M Bestvina
Principal Investigator
Ochsner Clinic Foundation
New Orleans Louisiana, 70121, United States More Info
Contact
504-842-3910
Marc R Matrana
Principal Investigator
University of Maryland Medical Center
Baltimore Maryland, 21201, United States More Info
Contact
410-328-8708
Christian Rolfo
Principal Investigator
Massachusetts General Hospital
Boston Massachusetts, 02114, United States More Info
Contact
617-726-2000
Lori Wirth
Principal Investigator
Dana-Farber Cancer Institute
Boston Massachusetts, 02215, United States More Info
Contact
617-632-2307
Jacob Sands
Principal Investigator
University of Michigan
Ann Arbor Michigan, 48109, United States More Info
Contact
734-764-1817
Francis Worden
Principal Investigator
START Midwest
Grand Rapids Michigan, 49546, United States More Info
Contact
616-954-5554
Nehal Lakhani
Principal Investigator
Mayo Clinic
Rochester Minnesota, 55905, United States More Info
Contact
5072844080
John Columbus Morris
Principal Investigator
Washington University Medical School
Saint Louis Missouri, 63110, United States More Info
Contact
314-362-7229
Saiama N Waqar
Principal Investigator
Comprehensive Cancer Centers of Nevada
Las Vegas Nevada, 89169, United States More Info
Contact
702-952-3400
Fadi S Braiteh
Principal Investigator
Roswell Park Cancer Institute
Buffalo New York, 14263, United States More Info
Contact
716-845-3099
Grace Dy
Principal Investigator
NYU Langone
New York New York, 10016, United States More Info
Contact
212-731-5662
Vamsidhar Velcheti
Principal Investigator
Memorial Sloan Kettering Cancer Center
New York New York, 10065, United States More Info
Contact
646-888-4206
Alexander Drilon
Principal Investigator
University of North Carolina
Chapel Hill North Carolina, 27599, United States More Info
Contact
866-869-1856
Jared Weiss
Principal Investigator
Cleveland Clinic Foundation
Cleveland Ohio, 44195, United States More Info
Contact
216-444-1128
Nathan Pennell
Principal Investigator
Ohio State University Hospital
Columbus Ohio, 43210, United States More Info
Contact
614-293-4680
Vineeth Sukrithan
Principal Investigator
Oregon Health and Science University
Portland Oregon, 97239, United States More Info
Contact
503-494-8534
Kyaw Z Thein
Principal Investigator
University of Pennsylvania Hospital
Philadelphia Pennsylvania, 19104, United States More Info
Contact
215-746-6344
Devraj Basu
Principal Investigator
Thomas Jefferson University
Philadelphia Pennsylvania, 19107, United States More Info
Marcia Brose
Principal Investigator
Sarah Cannon Research Institute SCRI
Nashville Tennessee, 37203, United States More Info
David Robert Spigel
Principal Investigator
Vanderbilt University Medical Center
Nashville Tennessee, 37232, United States More Info
Contact
6159368580
Jordan David Berlin
Principal Investigator
University of Texas Southwestern Medical Center at Dallas
Dallas Texas, 75390, United States More Info
Contact
214-648-4180
Tian Zhang
Principal Investigator
University of Texas MD Anderson Cancer Center
Houston Texas, 77030, United States More Info
Contact
713-745-6754
Vivek Subbiah
Principal Investigator
Huntsman Cancer Institute
Salt Lake City Utah, 84112, United States More Info
Contact
801-585-5986
Wallace L Akerley
Principal Investigator
Virginia Cancer Specialists, PC
Fairfax Virginia, 22031, United States More Info
Contact
703-280-5390
Alexander I Spira
Principal Investigator
University of Wisconsin-Madison Hospital and Health Clinic
Madison Wisconsin, 53792, United States More Info
Contact
608-262-2803
Mark Burkard
Principal Investigator
Royal North Shore Hospital
St. Leonards New South Wales, 2065, Australia More Info
Contact
61299267267
Bruce Robinson
Principal Investigator
Peter MacCallum Cancer Centre
Melbourne Victoria, 3000, Australia More Info
Contact
61385595000
Benjamin Solomon
Principal Investigator
BC Cancer Vancouver
Vancouver British Columbia, V5Z 4, Canada More Info
Contact
6048776000
Janessa Laskin
Principal Investigator
Rigshospitalet
Copenhagen København Ø, 2100, Denmark More Info
Contact
004535456353
Kristoffer Rohrberg
Principal Investigator
Hôpital Européen Georges Pompidou
Paris Cedex 15, 75908, France More Info
Contact
33156093714
Jacques Medioni
Principal Investigator
Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
Bordeaux , 33076, France More Info
Contact
556333244
Antoine Italiano
Principal Investigator
Centre Leon Berard
Lyon Cedex 08 , 69373, France More Info
Contact
33426556833
Philippe Cassier
Principal Investigator
APHM Hôpital de la Timone
Marseille , 13385, France More Info
Contact
33491385918
Pascale Tomasini
Principal Investigator
Institut du Cancer de Montpellier - Val d'aurelle
Montpellier Cedex 5 , 34298, France More Info
Contact
33467613100
Diego Tosi
Principal Investigator
Gustave Roussy
Villejuif Cedex , 94805, France More Info
Contact
33142114157
Benjamin Besse
Principal Investigator
Universitätsklinikum Würzburg A. ö. R.
Würzburg Bayern, 97080, Germany More Info
Contact
4993120139939
Barbara Deschler-Baier
Principal Investigator
Universitätsklinikum Köln
Köln Nordrhein-Westfalen, 50937, Germany More Info
Contact
492214783993
Jürgen Wolf
Principal Investigator
Prince of Wales Hospital
Hong Kong Shatin, New Territories, , Hong Kong More Info
Contact
85226322648
Herbert Ho Fung Loong
Principal Investigator
Sheba Medical Center
Tel Hashomer Ramat Gan, 52656, Israel More Info
Contact
972526667591
Talia Golan
Principal Investigator
Shaare Zedek Medical Center
Jerusalem Yerushalayim, 91031, Israel More Info
Nir Peled
Principal Investigator
Soroka Medical Center - Pediatric Outpatient Clinic
Beer-Sheva , 84101, Israel More Info
Contact
972587040620
Julia Dudnik
Principal Investigator
Hadassah Medical Center
Jerusalem , 91120, Israel More Info
Contact
972508946057
Hovav Nechushtan
Principal Investigator
Istituto Nazionale dei Tumori
Milano Lombardie, 20133, Italy More Info
Contact
390223902906
Filippo De Braud
Principal Investigator
Nagoya University Hospital
Nagoya Aichi, 466-8, Japan More Info
Contact
81527412111
Masahiro Morise
Principal Investigator
National Cancer Center Hospital East
Kashiwa Chiba, 277-8, Japan More Info
Contact
81471331111
Koichi Goto
Principal Investigator
Hokkaido University Hospital
Sapporo Hokkaido, 060-8, Japan More Info
Contact
81 117161161
Jun Sakakibara
Principal Investigator
Hyogo Cancer Center
Akashi Hyogo, 673-8, Japan More Info
Contact
81789291151
Miyako Satouchi
Principal Investigator
Kanazawa University Hospital
Kanazawa Ishikawa, 920-8, Japan More Info
Contact
81762652000
Shinji Takeuchi
Principal Investigator
Kindai University Hospital
Osaka Sayama-shi Osaka, 589 8, Japan More Info
Contact
81723660221
Tsutomu Iwasa
Principal Investigator
Shizuoka Cancer Center
Nagaizumi Shizuoka, 411-8, Japan More Info
Contact
81559895222
Hirotsugu Kenmotsu
Principal Investigator
National Cancer Center Hospital
Chuo-ku Tokyo, 104-0, Japan More Info
Contact
81335422511
YUICHIRO OHE
Principal Investigator
Japanese Foundation for Cancer Research
Koto Tokyo, 135-8, Japan More Info
Contact
81335200111
Makoto Nishio
Principal Investigator
Tottori University Hospital
Yonago Tottori, 683-8, Japan More Info
Contact
81859331111
Tomohiro Sakamoto
Principal Investigator
National Hospital Organization Kyushu Cancer Center
Fukuoka , 811-1, Japan More Info
Contact
81925413231
Ryo Toyozawa
Principal Investigator
Okayama University Hospital
Okayama , 700-8, Japan More Info
Contact
81862357226
Kadoaki Ohashi
Principal Investigator
Osaka City General Hospital
Osaka , 534-0, Japan More Info
Contact
81669291221
Haruko Daga
Principal Investigator
National Cancer Center
Goyang-si Gyeonggi-do, 10408, Korea, Republic of More Info
Contact
82319201154
Ji-Youn Han
Principal Investigator
Seoul National University Bundang Hospital
Seongnam Kyǒnggi-do, 13620, Korea, Republic of More Info
Contact
82317877005
Yu Jung Kim
Principal Investigator
Asan Medical Center
Seoul Seoul-teukbyeolsi [Seoul], 05505, Korea, Republic of More Info
Contact
8222243214
Dae Ho Lee
Principal Investigator
Samsung Medical Center
Seoul Seoul-teukbyeolsi [Seoul], 06351, Korea, Republic of More Info
Contact
82234101132
Se Hoon Lee
Principal Investigator
Severance Hospital, Yonsei University Health System
Seoul , 03722, Korea, Republic of More Info
Contact
82222280880
Byoung Chul Cho
Principal Investigator
National Cancer Centre Singapore
Singapore , 16961, Singapore More Info
Contact
6564368000
Shao Weng Daniel Tan
Principal Investigator
Hospital Universitari Vall d'Hebron
Barcelona Barcelona [Barcelona], 8035, Spain More Info
Contact
934893000
Elena Garralda Cabanas
Principal Investigator
Hospital Universitario Fundación Jiménez Díaz
Madrid , 28040, Spain More Info
Contact
34915504800
Victor Moreno
Principal Investigator
Hospital Madrid Norte Sanchinarro
Madrid , 28050, Spain More Info
Contact
917567800
Valentina Boni
Principal Investigator
Kantonsspital Luzern
Luzern 16 Luzern, 6000, Switzerland More Info
Contact
0041412056849
Oliver Gautschi
Principal Investigator
Taichung Veterans General Hospital
Taichung , 40705, Taiwan More Info
Contact
886423592525
Kuo-Hsuan Hsu
Principal Investigator
National Taiwan University Hospital
Taipei , 10002, Taiwan More Info
Chih-Hsin Yang
Principal Investigator
Royal Marsden Hospital
Sutton Surrey, SM2 5, United Kingdom More Info
Contact
02086426011
Anna Minchom
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Breast Cancer

Phase:

Phase 1

Estimated Enrollment:

875

Study ID:

NCT03157128

Recruitment Status:

Recruiting

Sponsor:


Loxo Oncology, Inc.

How clear is this clinincal trial information?

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