Phase 1 Study to Determine the MTD, Safety, Tolerability, PK and Preliminary Anti-tumor Effects of LNS8801alone and in Combination With Pembrolizumab

Summary

Participation Requirements

Description

In this Phase 1, first-in-human, open-label, multi-center study. Cohorts will enroll at least 3 patients in accordance with a traditional dose escalation 3+3 design, and the study will determine the MTD/RP2D of LNS8801. With permission from the Safety Review Committee (SRC), 2 cohorts may be expande...

In this Phase 1, first-in-human, open-label, multi-center study. Cohorts will enroll at least 3 patients in accordance with a traditional dose escalation 3+3 design, and the study will determine the MTD/RP2D of LNS8801. With permission from the Safety Review Committee (SRC), 2 cohorts may be expanded to include 8 to 10 patients to further explore PK and pharmacodynamics. LNS8801 will be administered 3 days/week or once or twice a day during 21 day cycle until disease progression or unacceptable toxicity occurs. Safety assessments will be performed on all patients at screening, throughout their participation in the study, and for 30 days (90 days in combination cohorts) following the last dose of study drug. Throughout the study, imaging of tumors for evidence of tumor response and/or progression will be performed; biopsies will be performed on accessible lesions. After the RP2D of LNS8801 is identified and the safety of dosing LNS8801 with pembrolizumab has been established, up to 27 patients who have previously had confirmed clinical benefit from a PD-1/L1 therapy (defined by stable disease, partial response, or complete response by RECIST v1.1 for at least 16 weeks) but have since relapsed on the same PD-1/L1 therapy will be dosed in expansion cohorts. The expansion cohorts will determine the effects of LNS8801 alone and in combination with pembrolizumab. LNS8801 capsules or tablets will be administered orally for 3 (Day 1 to Day 3) or 7 consecutive days per week (once or twice daily) for each 21 day cycle until disease progression or unacceptable toxicity occurs. Pembrolizumab will be dosed at 200 mg every 3 weeks with the first combination cohort to receive LNS8801 starting at the RP2D or one dose level below the MTD/RP2D determined in the monotherapy cohort. In the monotherapy expansion cohort, patients with a grade 3 immune related adverse event to prior immunotherapy will also be eligible for inclusion. Up to 100 patients will be accrued for this study at up to ten study sites in the United States.

Tracking Information