Bioequivalence and the Tolerability and Antitumor Activity of Selinexor Combination Treatment

Description

Monotherapy Period

For the Monotherapy Period of Study KCP-330-027, patients will be allocated to one of two test formulation treatment arms for once weekly dosing over a period of 3 weeks. A third test formulation of 100-mg oral suspension will be allocated on Week 3 to 6 patients in total out of the 38 patients planned to be enrolled. Approximately 38 patients will be enrolled, with a maximum of 20 patients for each disease type (NSCLC or CRC). In the CRC Cohort, at least 10 patients should have the KRAS mutation. Patients will be randomized to 1 of the 2 treatment arms; disease type (NSCLC or CRC) will be a randomization factor. The number of patients enrolled may be adjusted based on the results of the interim analysis performed after the first 16 pharmacokinetics (PK) evaluable patients have completed Week 2.

For Weeks 1 and 2 (and Week 3 for patients receiving the 100-mg oral suspension), following an overnight fast of at least 10 hours, patients will be fed a standard low-fat meal 30 minutes prior to administration of once weekly selinexor. Patients should finish the meal in 30 minutes or less; however, selinexor dose should be administered 30 minutes after start of the meal. Blood sampling for selinexor PK analyses will be collected predose (10 minutes before taking selinexor), 15 min (3 min), 30 min (3 min), 1 hour (5 min), 1.5 hours (7 min), 2 hours (10 min), 3 hours (10 min), 4 hours (10 min), 5 hours (10 min), 6 hours (10 min), 8 hours (20 min), 10 hours (20 min; optional timepoint), 24 hours (30 min), 30 hours (30 min), and 48 hours (1 hour) post selinexor dose. Practitioners must record the actual clock time for selinexor dose and each sample drawn.

If a patient experiences emesis during the first 6 hours of the PK sampling, the results will be excluded from the PK analysis dataset.

Safety will be evaluated through reporting of treatment-emergent adverse events (TEAEs), physical examinations (PE), and clinical laboratory testing.

Computed tomography (CT) or magnetic resonance imaging (MRI) will be performed at screening.

Patients who complete the Monotherapy Period will be considered for continuation to the Combination Therapy Period if they do not meet any exclusion criteria for reassessment. If a patient experiences significant toxicity related to selinexor and can't start the combination therapy immediately following monotherapy, dose interruption and weekly retesting are allowed for up to 21 days after the End of Monotherapy Treatment Visit. Patients requiring >21 days to recover from toxicities related to selinexor should be discussed with the Sponsor's Medical Monitor for documented approval to continue to the Combination Therapy Period. Reassessment may be extended then and following Medical Monitor approval up to 28 days.

Combination Therapy Period Patients enrolled in the Combination Therapy Period will receive combination treatment with selinexor once weekly and either docetaxel (NSCLC patients) or pembrolizumab (CRC patients) every 3 weeks until progressive disease (PD) or intolerable toxicity.

Safety will be assessed through the continuous reporting of AEs, regularly scheduled clinical laboratory tests (hematologic and chemical), and physical examinations.

Tumor assessment will be performed with either CT or MRI (CT with contrast preferred; for each patient, the imaging method should remain the same throughout the study).

Patients will be followed for up to 1 year after the 30-Day Safety Visit (approximately 30 days after the last dose of combination therapy). Patients who discontinued due to PD will be followed for survival, and patients who discontinued for reasons other than PD will have tumor assessments until PD or until the start of new anti-neoplastic therapy and will be followed for survival.

Details