Testing the Addition of an Anti-cancer Drug, BAY 1895344, to Usual Chemotherapy for Advanced Stage Solid Tumors, With a Specific Focus on Patients With Small Cell Lung Cancer, Poorly Differentiated Neuroendocrine Cancer, and Pancreatic Cancer

Summary

Participation Requirements

Description

PRIMARY OBJECTIVES: I. To assess safety and tolerability of each of the ATR kinase inhibitor BAY1895344 (BAY 1895344) plus topoisomerase 1 (top1) inhibitor (liposomal irinotecan [irinotecan liposome] [nal-IRI] or topotecan hydrochloride [topotecan]) combinations. II. To estimate maximum tolerated do...

PRIMARY OBJECTIVES: I. To assess safety and tolerability of each of the ATR kinase inhibitor BAY1895344 (BAY 1895344) plus topoisomerase 1 (top1) inhibitor (liposomal irinotecan [irinotecan liposome] [nal-IRI] or topotecan hydrochloride [topotecan]) combinations. II. To estimate maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of each of the combinations. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To estimate objective response rate (ORR), progression free survival (PFS), overall survival (OS) and duration of response (DOR) in patients treated with each combination. III. To estimate plasma pharmacokinetic (PK) characteristics of BAY 1895344 plus each top1 inhibitor (nal-IRI or topotecan) when used in combination. IV. To estimate changes in pharmacodynamic (PD) markers of deoxyribonucleic acid (DNA) damage (gamma-H2AX, pS343-NBS1) elicited by each combination from on-treatment tumor biopsies (in dose expansion cohorts only). EXPLORATORY OBJECTIVES: I. To estimate response outcomes (ORR, PFS, OS, DOR) in study patients by tumor ataxia telangiectasia mutated (ATM) expression loss (assessed by immunohistochemistry [IHC]). II. To estimate response outcomes (ORR, PFS, OS, DOR) in study patients with tumor DNA damage response (DDR) mutations (assessed by whole exome sequencing [WES] and ribonucleic acid [RNA] sequencing [RNA Seq]). OUTLINE: This is a dose-escalation study of BAY 1895344. Patients are assigned to 1 of 2 cohorts. COHORT I: Patients receive BAY 1895344 orally (PO) twice daily (BID) on days 1 and 2 and irinotecan liposome intravenously (IV) over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. COHORT II: Patients receive topotecan IV over 30 minutes on days 1-5 and BAY 1895344 PO BID on days 2 and 5. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 6 months.

Tracking Information