PHASE 1 STUDY OF LOXO-292 IN PATIENTS WITH ADVANCED SOLID TUMORS, RET-FUSION LUNG CANCER AND MEDULLARY THYROID CANCER

Loxo Oncology

Cancers solides dont cancer médullaire de la thyroïde et cancer bronchique non à petites cellules avec activation de RET

Interventionnelle

Phase I

105

clinicaltrials@loxooncology.com

Etats Unis, Corée, Espagne, France: Institut Gustave Roussy

Maximum tolerated dose (MTD) [ Time Frame: The first 28 days of treatment (Cycle 1) ]

Recommended dose for further study [ Time Frame: The first 28 days of treatment (Cycle 1) and every cycle (28 days) for approximately 12 months (or earlier if the patient discontinues from the study) ]

· Diagnosis during Dose Escalation (Part 1) – Locally advanced or metastatic solid tumor refractory to standard of care therapy, or for whom no standard of care therapy is available, or who in the opinion of the Investigator, is not a candidate for, or would be unlikely to tolerate or derive significant clinical benefit from standard of care therapy.

· Once a safe dose level is achieved that is consistent with inhibiting RET, patients must have advanced NSCLC, MTC or other advanced solid tumor with evidence of RET alteration or other evidence of increased RET activity in tumor tissue and/or blood.

· Any number of prior TKIs.

· 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.

· Adequate hematologic, hepatic and renal function.

· Life expectancy of at least 3 months

For MTC: PD within the previous 14 months as defined by RECIST 1.1.

•    For NSCLC patients, a targetable mutation in EGFR, or targetable rearrangement involving ALK or ROS1.
•    Investigational agent or anticancer therapy within 2 weeks (14 days) prior to planned start of LOXO-292.
•    Major surgery (excluding placement of vascular access) within 4 weeks prior to planned start of LOXO-292.
•    Radiotherapy with a limited field of radiation for palliation within 1 week of planned start of LOXO-292, with the exception of patients 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.
•    Symptomatic primary CNS tumor or metastases (stable CNS tumor/metastases is allowed).
•    Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292 or prolongation of the QT interval corrected (QTcF) > 470 msec.
•    Required treatment with certain strong CYP3A4 inhibitors or inducers.