Testing the Addition of an Anti-cancer Drug, BAY 1895344, to the Usual Chemotherapy Treatment (Cisplatin, or Cisplatin and Gemcitabine) for Advanced Solid Tumors With Emphasis on Urothelial Cancer

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PRIMARY OBJECTIVES: I. To establish the safety and tolerability of the combination of cisplatin + ATR kinase inhibitor BAY1895344 (BAY 1895344) in patients with advanced solid tumors. II. To establish the safety and tolerability of the combination of cisplatin + gemcitabine + BAY 1895344 in patients...

PRIMARY OBJECTIVES: I. To establish the safety and tolerability of the combination of cisplatin + ATR kinase inhibitor BAY1895344 (BAY 1895344) in patients with advanced solid tumors. II. To establish the safety and tolerability of the combination of cisplatin + gemcitabine + BAY 1895344 in patients with advanced solid tumors with an emphasis on urothelial carcinoma (UC). III. To establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of cisplatin + BAY 1895344 and cisplatin + gemcitabine + BAY 1895344. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To evaluate the pharmacokinetic profile of BAY 1895344 (in the doublet and triplet combinations) and gemcitabine (in the triplet) in combination with cisplatin. III. To further evaluate the toxicity of the combination of cisplatin + gemcitabine + BAY 1895344 in patients with UC. IV. To evaluate preliminary efficacy observed with cisplatin + BAY 1895344 and cisplatin + gemcitabine + BAY 1895344 in patients with advanced solid tumors, including UC. V. To evaluate the association between ATM expression by immunohistochemical staining and responses to therapy. EXPLORATORY OBJECTIVES: I. To evaluate the responses to therapy using whole exome sequencing (WES) and messenger ribonucleic acid (RNA) sequencing (RNA Seq) analysis of archival formalin fixed paraffin embedded (FFPE) tissue. II. To correlate drug exposure with response and/or toxicity. OUTLINE: This is a dose-escalation study of BAY 1895344. Patients are assigned to 1 of 2 arms. ARM I (DOUBLET COMBINATION): Patients receive cisplatin intravenously (IV) over 1-2 hours on day 1, and BAY 1895344 orally (PO) twice daily (BID) on days 2 and 9. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. ARM II (TRIPLET COMBINATION): Patients receive cisplatin IV over 1-2 hours on day 1, gemcitabine IV over 30 minutes on days 1 and 8, and BAY 1895344 PO BID on days 2 and 9. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, then every 3 months thereafter.

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