Clinical Trial - NCT03157128

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

Recruiting

Sponsor: Loxo Oncology, Inc.

Collaborators: Eli Lilly and Company

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03157128

Protocol Info

Short Description: Phase 1 LOXO-292 in Advanced Solid Tumors
Long Description: A Phase 1/2 Study of Oral LOXO-292 in Patients with Advanced Solid Tumors, Including RET Fusion-Positive Solid Tumors, Medullary Thyroid Cancer, and Other Tumors with RET Activation (LIBRETTO-001)
MGH Status: Open
Sponsor: Loxo Oncology Inc.
Disease Program: Head & Neck

Next Steps


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Purpose

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.
Condition Title Intervention Phase
Non-Small Cell Lung Cancer Medullary Thyroid Cancer Colon Cancer Any Solid Tumor LOXO-292 Phase 1/Phase 2
Study Type Interventional
Official Title A Study of Oral LOXO-292 in Patients With Advanced Solid Tumors, Including RET Fusion-Positive Solid Tumors, Medullary Thyroid Cancer, and Other Tumors With RET Activation (LIBRETTO-001)

Primary Outcome Measures

Phase 1: MTD [Time Frame: The first 28 days of treatment (Cycle 1)] [Designated as safety issue: ]

Phase 1: RP2D [Time Frame: The first 28 days of treatment (Cycle 1) and every cycle (28 days) for approximately 12 months (or earlier if the participant discontinues from the study)] [Designated as safety issue: ]

Phase 2: Objective Response Rate [Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in participants who have not progressed.] [Designated as safety issue: ]


Secondary Outcome Measures

Phase 1: Number of Participants with a Treatment-Related Adverse Event(s) (TRAE[s]) [Time Frame: From the time of informed consent, for approximately 24 months (or earlier if the participant discontinues from the study), and through Safety Follow-up (28 days after the last dose)] [Designated as safety issue: ]

Phase 1: Number of Participants with an Abnormal Laboratory or Physical Exam Result(s) [Time Frame: From the time of informed consent, for approximately 24 months (or earlier if the participant discontinues from the study), and through Safety Follow-up (28 days after the last dose)] [Designated as safety issue: ]

Phase 1: Overall Response Rate (ORR) based on RECIST 1.1 or RANO, as Appropriate to Tumor Type [Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed] [Designated as safety issue: ]

Phase 2: ORR (by Investigator) [Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed] [Designated as safety issue: ]

Phase 2: Best Change in Tumor Size from Baseline (by IRC and Investigator) [Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed] [Designated as safety issue: ]

Phase 2: Duration of Response (DOR; by IRC and Investigator) [Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed] [Designated as safety issue: ]

Phase 2: Central Nervous System (CNS) ORR (by IRC) [Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed] [Designated as safety issue: ]

Phase 2: CNS DOR (by IRC) [Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed] [Designated as safety issue: ]

Phase 2: Time to Any and Best Response (by IRC and Investigator) [Time Frame: every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed] [Designated as safety issue: ]

Phase 2: CBR (by IRC and Investigator) [Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed] [Designated as safety issue: ]

Phase 2: PFS (by IRC and Investigator) [Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed] [Designated as safety issue: ]

Phase 2: Overall Survival (OS) [Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed] [Designated as safety issue: ]

Phase 2: Percentage of Participants with any Serious Adverse Event (SAE[s]) [Time Frame: From the time of informed consent, for approximately 24 months (or earlier if the participant discontinues from the study), and through Safety Follow-up (28 days after the last dose)] [Designated as safety issue: ]

Phase 1 and 2: Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve of LOXO-292 (Selpercatinib) [Time Frame: Cycle 1 Day 1 through Cycle 5 Day 1 (Cycle = 28 days)] [Designated as safety issue: ]

Phase 1 and 2: PK: Maximum Concentration (Cmax) of LOXO-292 (Selpercatinib) [Time Frame: Cycle 1 Day 1 through Cycle 5 Day 1 (Cycle = 28 days)] [Designated as safety issue: ]

Estimated Enrollment: 989
Study Start Date: May 2017
Estimated Study Completion Date: November 2023
Estimated Primary Completion Date: November 2022
Arms Assigned Interventions

Experimental:LOXO-292

Phase 1 - Multiple doses of LOXO-292 (selpercatinib) Phase 2 - The maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D)
Drug:LOXO-292
Oral LOXO-292

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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:
  • Without measurable disease but otherwise meet criteria for Cohorts 1 and 2;
  • 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 due to intolerance may be eligible with prior Sponsor approval
  • Cohort 7: Participants must have a histologically confirmed stage IB-IIIA NSCLC by AJCC (The American Joint Committee on Cancer) version 8. The tumor must have been deemed resectable by a thoracic surgeon, the participant must be determined to be medically operable based on the determination of a thoracic surgeon, and the participant must not have received prior systemic therapy, including prior radiation therapy, 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 4 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)
  • Required treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and certain prohibited concomitant medications

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03157128

Locations

  • United States, Arizona
    • Mayo Clinic of Scottsdale Scottsdale, Arizona, United States, 85259
  • United States, California
    • City of Hope National Medical Center Duarte, California, United States, 91010-0269
    • University of California - San Diego La Jolla, California, United States, 92161
    • UCLA Medical Center Los Angeles, California, United States, 90095
    • Hoag Memorial Hospital Presbyterian Newport Beach, California, United States, 92663
    • Irvine Medical Center Orange, California, United States, 92868
    • UCSF Medical Center at Mission Bay San Francisco, California, United States, 94115
    • Kaiser Permanente Santa Clara, California, United States, 95051
    • Kaiser Permanente Medical Center Vallejo, California, United States, 94589
  • United States, Colorado
    • Sarah Cannon Research Institute at HealthOne Denver, Colorado, United States, 80218
  • United States, Connecticut
    • Yale Cancer Center New Haven, Connecticut, United States, 06510
  • United States, District of Columbia
    • Johns Hopkins University Washington, District of Columbia, United States, 20016
  • United States, Florida
    • Mayo Clinic-Jacksonville Jacksonville, Florida, United States, 32224
    • Memorial Hospital Pembroke Pembroke, Florida, United States, 33028
  • United States, Georgia
    • Emory University Atlanta, Georgia, United States, 30322
  • United States, Illinois
    • University of Chicago Medicine-Comprehensive Cancer Center Chicago, Illinois, United States, 60637
  • United States, Louisiana
    • Ochsner Clinic Foundation New Orleans, Louisiana, United States, 70121
  • United States, Maryland
    • University of Maryland Medical Center Baltimore, Maryland, United States, 21201
  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
    • Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02215
  • United States, Michigan
    • University of Michigan Ann Arbor, Michigan, United States, 48109
    • START Midwest Grand Rapids, Michigan, United States, 49546
  • United States, Minnesota
    • Mayo Clinic Rochester, Minnesota, United States, 55905
  • United States, Missouri
    • Washington University Medical School Saint Louis, Missouri, United States, 63110
  • United States, Nevada
    • Comprehensive Cancer Centers of Nevada Las Vegas, Nevada, United States, 89169
  • United States, New York
    • Roswell Park Cancer Institute Buffalo, New York, United States, 14263-0002
    • NYU Langone New York, New York, United States, 10016
    • Memorial Sloan Kettering Cancer Center New York, New York, United States, 10065
  • United States, North Carolina
    • University of North Carolina Chapel Hill, North Carolina, United States, 27599-7305
  • United States, Ohio
    • Cleveland Clinic Foundation Cleveland, Ohio, United States, 44195
    • Ohio State University Hospital Columbus, Ohio, United States, 43210
  • United States, Oregon
    • Oregon Health and Science University Portland, Oregon, United States, 97239
  • United States, Pennsylvania
    • University of Pennsylvania Hospital Philadelphia, Pennsylvania, United States, 19104
  • United States, Tennessee
    • Sarah Cannon Research Institute SCRI Nashville, Tennessee, United States, 37203
    • Vanderbilt University Medical Center Nashville, Tennessee, United States, 37232-6307
  • United States, Texas
    • University of Texas Southwestern Medical Center at Dallas Dallas, Texas, United States, 75390
    • University of Texas MD Anderson Cancer Center Houston, Texas, United States, 77030
  • United States, Utah
    • Huntsman Cancer Institute Salt Lake City, Utah, United States, 84112
  • United States, Virginia
    • Virginia Cancer Specialists, PC Fairfax, Virginia, United States, 22031
  • United States, Wisconsin
    • University of Wisconsin-Madison Hospital and Health Clinic Madison, Wisconsin, United States, 53792
  • Australia, New South Wales
    • Royal North Shore Hospital St. Leonards, New South Wales, Australia, 2065
  • Australia, Victoria
    • Peter MacCallum Cancer Centre Melbourne, Victoria, Australia, 3000
  • Canada, British Columbia
    • British Columbia Cancer Agency Vancouver, British Columbia, Canada, V5Z 4E6
  • Denmark, København Ø
    • Rigshospitalet Copenhagen, København Ø, Denmark, 2100
  • France, Cedex 15
    • Hôpital Européen Georges Pompidou Paris, Cedex 15, France, 75908
  • France,
    • Institut Bergonie Bordeaux, , France, 33076
    • Centre Leon Berard Lyon Cedex 08, , France, 69373
    • APHM Hôpital de la Timone Marseille, , France, 13385
    • Institut du Cancer de Montpellier - Val d'aurelle Montpellier Cedex 5, , France, 34298
    • Gustave Roussy Villejuif Cedex, , France, 94805
  • Germany, Bayern
    • Universitätsklinikum Würzburg A. ö. R. Würzburg, Bayern, Germany, 97080
  • Germany, Nordrhein-Westfalen
    • Universitätsklinikum Köln Köln, Nordrhein-Westfalen, Germany, 50937
  • Hong Kong, Shatin, New Territories
    • Prince of Wales Hospital Hong Kong, Shatin, New Territories, Hong Kong,
  • Israel, Ramat Gan
    • Sheba Medical Center Tel Hashomer, Ramat Gan, Israel, 5265601
  • Israel,
    • Soroka Medical Center - Pediatric Outpatient Clinic Beer-Sheva, , Israel, 8410101
    • Hadassah Medical Center Jerusalem, , Israel, 91120
  • Italy, Lombardie
    • Istituto Nazionale dei Tumori Milano, Lombardie, Italy, 20133
  • Japan, Aichi
    • Nagoya University Hospital Nagoya, Aichi, Japan, 466-8560
  • Japan, Chiba
    • National Cancer Center Hospital East Kashiwa, Chiba, Japan, 277 8577
  • Japan, Hokkaido
    • Hokkaido University Hospital Sapporo, Hokkaido, Japan, 060-8648
  • Japan, Hyogo
    • Hyogo Cancer Center Akashi, Hyogo, Japan, 673-8558
  • Japan, Ishikawa
    • Kanazawa University Hospital Kanazawa, Ishikawa, Japan, 920 8641
  • Japan, Osaka
    • Kindai University Hospital Osaka Sayama-shi, Osaka, Japan, 589 8511
  • Japan, Shizuoka
    • Shizuoka Cancer Center Sunto-Gun, Shizuoka, Japan, 411-8777
  • Japan, Tokyo
    • National Cancer Center Hospital Chuo-ku, Tokyo, Japan, 104-0045
    • The Cancer Institute Hospital of JFCR Koto-ku, Tokyo, Japan, 135-8550
  • Japan, Tottori
    • Tottori University Hospital Yonago, Tottori, Japan, 683-0826
  • Japan,
    • Kyushu Cancer Center Fukuoka, , Japan, 811-1395
    • Okayama University Hospital Okayama, , Japan, 700-8558
    • Osaka City General Hospital Osaka, , Japan, 534-0021
  • Korea, Republic of, Geonggi-do
    • Seoul National University Bundang Hospital Seongnam, Geonggi-do, Korea, Republic of, 13620
  • Korea, Republic of, Gyeonggi-do
    • National Cancer Center Goyang-si, Gyeonggi-do, Korea, Republic of, 10408
  • Korea, Republic of, Seoul-teukbyeolsi [Seoul]
    • Asan Medical Center Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of, 05505
    • Samsung Medical Center Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of, 06351
  • Korea, Republic of,
    • Severance Hospital Seoul, , Korea, Republic of, 03722
  • Singapore,
    • National Cancer Center Singapore Singapore, , Singapore, 169610
  • Spain,
    • Hospital Universitari Vall d'Hebron Barcelona, , Spain, 08035
    • Fundacion Jimenez Diaz Madrid, , Spain, 28040
    • Hospital Madrid Norte Sanchinarro Madrid, , Spain, 28050
  • Switzerland, Luzern
    • Kantonsspital Luzern Luzern 16, Luzern, Switzerland, 6000
  • Taiwan,
    • Taichung Veterans General Hospital Taichung, , Taiwan, 40705, ROC
    • National Taiwan University Hospital Taipei, , Taiwan, 10002
  • United Kingdom, Surrey
    • Royal Marsden Hospital Sutton, Surrey, United Kingdom, SM2 5PT

Sponsors and Collaborators

Loxo Oncology, Inc.

Eli Lilly and Company

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03157128
Other Study ID Numbers: J2G-OX-JZJA
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Eli Lilly and Company:

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

Additional relevant MeSH terms:

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Colonic Neoplasms

Thyroid Neoplasms

Carcinoma, Neuroendocrine

Thyroid Diseases

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on June 16, 2021