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.
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)
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.
Check Your Eligibility
Let’s see if you might be eligible for this study.
What is your age and gender ?
There are 84 Locations for this study
Scottsdale Arizona, 85259, United States More Info
Principal Investigator
Duarte California, 91010, United States More Info
Principal Investigator
La Jolla California, 92161, United States More Info
Principal Investigator
Los Angeles California, 90095, United States More Info
Principal Investigator
Newport Beach California, 92663, United States More Info
Principal Investigator
Orange California, 92868, United States More Info
Principal Investigator
San Francisco California, 94115, United States More Info
Principal Investigator
Santa Clara California, 95051, United States More Info
Principal Investigator
Vallejo California, 94589, United States More Info
Principal Investigator
Denver Colorado, 80218, United States More Info
Principal Investigator
New Haven Connecticut, 06510, United States More Info
Principal Investigator
Washington District of Columbia, 20016, United States More Info
Principal Investigator
Jacksonville Florida, 32224, United States More Info
Principal Investigator
Pembroke Florida, 33028, United States More Info
Principal Investigator
Atlanta Georgia, 30322, United States More Info
Principal Investigator
Chicago Illinois, 60637, United States More Info
Principal Investigator
New Orleans Louisiana, 70121, United States More Info
Principal Investigator
Baltimore Maryland, 21201, United States More Info
Principal Investigator
Boston Massachusetts, 02114, United States More Info
Principal Investigator
Boston Massachusetts, 02215, United States More Info
Principal Investigator
Ann Arbor Michigan, 48109, United States More Info
Principal Investigator
Grand Rapids Michigan, 49546, United States More Info
Principal Investigator
Rochester Minnesota, 55905, United States More Info
Principal Investigator
Saint Louis Missouri, 63110, United States More Info
Principal Investigator
Las Vegas Nevada, 89169, United States More Info
Principal Investigator
Buffalo New York, 14263, United States More Info
Principal Investigator
New York New York, 10016, United States More Info
Principal Investigator
New York New York, 10065, United States More Info
Principal Investigator
Chapel Hill North Carolina, 27599, United States More Info
Principal Investigator
Cleveland Ohio, 44195, United States More Info
Principal Investigator
Columbus Ohio, 43210, United States More Info
Principal Investigator
Portland Oregon, 97201, United States More Info
Principal Investigator
Philadelphia Pennsylvania, 19104, United States More Info
Principal Investigator
Philadelphia Pennsylvania, 19107, United States More Info
Principal Investigator
Nashville Tennessee, 37203, United States More Info
Principal Investigator
Nashville Tennessee, 37232, United States More Info
Principal Investigator
Dallas Texas, 75390, United States More Info
Principal Investigator
Houston Texas, 77030, United States More Info
Principal Investigator
Salt Lake City Utah, 84112, United States More Info
Principal Investigator
Fairfax Virginia, 22031, United States More Info
Principal Investigator
Madison Wisconsin, 53792, United States More Info
Principal Investigator
St. Leonards New South Wales, 2065, Australia More Info
Principal Investigator
Melbourne Victoria, 3000, Australia More Info
Principal Investigator
Vancouver British Columbia, V5Z 4, Canada More Info
Principal Investigator
Copenhagen København Ø, 2100, Denmark More Info
Principal Investigator
Paris Cedex 15, 75908, France More Info
Principal Investigator
Marseille , 13385, France More Info
Principal Investigator
Montpellier Cedex 5 , 34298, France More Info
Principal Investigator
Würzburg Bayern, 97080, Germany More Info
Principal Investigator
Köln Nordrhein-Westfalen, 50937, Germany More Info
Principal Investigator
Hong Kong Shatin, New Territories, , Hong Kong More Info
Principal Investigator
Tel Hashomer Ramat Gan, 52656, Israel More Info
Principal Investigator
Jerusalem Yerushalayim, 91031, Israel More Info
Principal Investigator
Beer-Sheva , 84101, Israel More Info
Principal Investigator
Milano Lombardie, 20133, Italy More Info
Principal Investigator
Nagoya Aichi, 466-8, Japan More Info
Principal Investigator
Kashiwa Chiba, 277-8, Japan More Info
Principal Investigator
Sapporo Hokkaido, 060-8, Japan More Info
Principal Investigator
Kanazawa Ishikawa, 920-8, Japan More Info
Principal Investigator
Osaka Sayama-shi Osaka, 589 8, Japan More Info
Principal Investigator
Nagaizumi Shizuoka, 411-8, Japan More Info
Principal Investigator
Chuo-ku Tokyo, 104-0, Japan More Info
Principal Investigator
Koto Tokyo, 135-8, Japan More Info
Principal Investigator
Yonago Tottori, 683-8, Japan More Info
Principal Investigator
Fukuoka , 811-1, Japan More Info
Principal Investigator
Goyang-si Gyeonggi-do, 10408, Korea, Republic of More Info
Principal Investigator
Seongnam KyÇ’nggi-do, 13620, Korea, Republic of More Info
Principal Investigator
Seoul Seoul-teukbyeolsi [Seoul], 05505, Korea, Republic of More Info
Principal Investigator
Seoul Seoul-teukbyeolsi [Seoul], 06351, Korea, Republic of More Info
Principal Investigator
Seoul , 03722, Korea, Republic of More Info
Principal Investigator
Singapore , 16961, Singapore More Info
Principal Investigator
Luzern 16 Luzern, 6000, Switzerland More Info
Principal Investigator
Taichung , 40705, Taiwan More Info
Principal Investigator
Taipei , 10002, Taiwan More Info
Principal Investigator
Sutton Surrey, SM2 5, United Kingdom More Info
Principal Investigator
How clear is this clinincal trial information?