A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001) (LIBRETTO-001)
Non-Small Cell Lung Cancer, Medullary Thyroid Cancer, Colon Cancer
About this trial
This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring 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
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.
Sites / Locations
- Mayo Clinic of ScottsdaleRecruiting
- City of Hope National Medical CenterRecruiting
- University of California - San DiegoRecruiting
- Hoag Memorial Hospital Presbyterian
- Irvine Medical CenterRecruiting
- UCSF Medical Center at Mission BayRecruiting
- Sarah Cannon Research Institute at HealthOneRecruiting
- Yale Cancer CenterRecruiting
- Johns Hopkins UniversityRecruiting
- Mayo Clinic in FloridaRecruiting
- Memorial Hospital PembrokeRecruiting
- Emory UniversityRecruiting
- University of Chicago Medicine-Comprehensive Cancer CenterRecruiting
- Ochsner Clinic FoundationRecruiting
- University of Maryland Medical CenterRecruiting
- Dana-Farber Cancer InstituteRecruiting
- University of MichiganRecruiting
- START MidwestRecruiting
- Mayo ClinicRecruiting
- Washington University Medical SchoolRecruiting
- Roswell Park Cancer InstituteRecruiting
- NYU LangoneRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- University of North CarolinaRecruiting
- Cleveland Clinic FoundationRecruiting
- Ohio State University HospitalRecruiting
- Oregon Health and Science UniversityRecruiting
- University of Pennsylvania HospitalRecruiting
- Thomas Jefferson UniversityRecruiting
- Sarah Cannon Research Institute SCRIRecruiting
- Vanderbilt University Medical CenterRecruiting
- University of Texas Southwestern Medical Center at DallasRecruiting
- Huntsman Cancer InstituteRecruiting
- USO-Virginia Cancer Specialists, PCRecruiting
- University of Wisconsin-Madison Hospital and Health ClinicRecruiting
- Royal North Shore HospitalRecruiting
- BC Cancer VancouverRecruiting
- RigshospitaletRecruiting
- Hôpital Européen Georges PompidouRecruiting
- Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud OuestRecruiting
- Centre Leon BerardRecruiting
- APHM Hôpital de la TimoneRecruiting
- Institut du Cancer de Montpellier - Val d'aurelle
- Universitätsklinikum Würzburg A. ö. R.Recruiting
- Universitätsklinikum KölnRecruiting
- Sheba Medical CenterRecruiting
- Shaare Zedek Medical Center
- Soroka Medical Center - Pediatric Outpatient ClinicRecruiting
- Hadassah Medical CenterRecruiting
- Istituto Nazionale dei TumoriRecruiting
- Nagoya University HospitalRecruiting
- National Cancer Center Hospital EastRecruiting
- Hokkaido University HospitalRecruiting
- Hyogo Cancer CenterRecruiting
- Kanazawa University HospitalRecruiting
- Kindai University HospitalRecruiting
- Tominaga HospitalRecruiting
- National Cancer Center HospitalRecruiting
- Japanese Foundation for Cancer ResearchRecruiting
- Tottori University HospitalRecruiting
- National Hospital Organization Kyushu Cancer CenterRecruiting
- Okayama University HospitalRecruiting
- Osaka City General HospitalRecruiting
- National Cancer CenterRecruiting
- Seoul National University Bundang HospitalRecruiting
- Asan Medical CenterRecruiting
- Samsung Medical CenterRecruiting
- Severance Hospital, Yonsei University Health SystemRecruiting
- National Cancer Centre SingaporeRecruiting
- Hospital Universitari Vall d'HebronRecruiting
- Hospital Universitario Fundación Jiménez DíazRecruiting
- Hospital Madrid Norte SanchinarroRecruiting
- Kantonsspital LuzernRecruiting
- Taichung Veterans General HospitalRecruiting
- National Taiwan University HospitalRecruiting
- Royal Marsden HospitalRecruiting
Arms of the Study
Arm 1
Experimental
LOXO-292
Phase 1 - Multiple doses of LOXO-292 (selpercatinib) Phase 2 - The maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D)