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

Running, not enrolling · Phase 1

Conditions studied: Advanced Bile Duct Carcinoma, Advanced Breast Carcinoma, Advanced Cervical Carcinoma, Advanced Endometrial Carcinoma, Advanced Esophageal Carcinoma, Advanced Gastric Carcinoma, Advanced Head and Neck Carcinoma, Advanced Lung Non-Small Cell Carcinoma, Advanced Lung Small Cell Carcinoma, Advanced Malignant Solid Neoplasm, Advanced Ovarian Carcinoma, Advanced Penile Carcinoma, Advanced Pleural Malignant Mesothelioma, Advanced Urothelial Carcinoma, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Clinical Stage III Gastric Cancer AJCC v8, Clinical Stage IV Gastric Cancer AJCC v8, Stage III Cervical Cancer AJCC v8, Stage III Distal Bile Duct Cancer AJCC v8, Stage III Intrahepatic Bile Duct Cancer AJCC v8, Stage III Lung Cancer AJCC v8, Stage III Ovarian Cancer AJCC v8, Stage III Penile Cancer AJCC v8, Stage III Pleural Diffuse Malignant Mesothelioma AJCC v8, Stage IV Cervical Cancer AJCC v8, Stage IV Distal Bile Duct Cancer AJCC v8, Stage IV Intrahepatic Bile Duct Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, Stage IV Ovarian Cancer AJCC v8, Stage IV Penile Cancer AJCC v8, Stage IV Pleural Diffuse Malignant Mesothelioma AJCC v8, Triple-Negative Breast Carcinoma, Unresectable Urothelial Carcinoma

In brief

This phase I trial identifies the best dose, possible benefits and/or side effects of BAY 1895344 in combination with chemotherapy in treating patients with solid tumors or urothelial cancer that has spread to other places in the body (advanced). BAY 1895344 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Cisplatin and gemcitabine are chemotherapy drugs that stop the growth of tumor cells by killing the cells. Combining BAY 1895344 with chemotherapy treatment (cisplatin, or cisplatin and gemcitabine) may be effective for the treatment of advanced solid tumors, including urothelial cancer.

Key facts

Study ID

NCT04491942

Run by

National Cancer Institute (NCI)

People needed

74

Starts

2021-08-25

Expected to finish

2027-06-30

Last updated by the study team

2026-07-31

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Histologically-confirmed advanced solid tumor with measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria, for which cisplatin-based therapy would be considered appropriate, including:
• Non-small cell lung cancer (NSCLC)
• UC
• Penile cancer
• Malignant pleural mesothelioma
• Small cell lung cancer
• Biliary tract cancer
• Esophageal and gastric cancers
• Ovarian cancer
• Endometrial cancer
• Cervical cancer
• Head and neck cancer
• Triple-negative breast cancer (Her2/neu-negative, estrogen receptor [ER]/progesterone receptor [PR]-negative breast cancer)
• For the expansion cohort of the triplet combination at MTD/RP2D only:
• Patients with histologically confirmed advanced or unresectable urothelial carcinoma are eligible
• The histology should be predominantly urothelial (>= 50% of sample evaluated contains urothelial histology)
• Age >= 18 years. Because no dosing or adverse event data are currently available on the use of BAY 1895344 in combination with gemcitabine and cisplatin in patients < 18 years of age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Availability of archival FFPE tissue
• Prior cisplatin exposure of < 300 mg/m\^2. Patients with prior cisplatin treatment must have received last cisplatin treatment > 6 months prior to enrollment
• Prior treatment with PARP inhibitors is permitted (such as olaparib, rucaparib, or other experimental inhibitors of PARP administered in a clinical trial)
• Prior immune checkpoint inhibitor therapy is permitted (including anti-programmed cell death protein 1 [PD-1], anti-PD-ligand [L]1 therapy, such as pembrolizumab, nivolumab, avelumab, durvalumab, atezolizumab, or anti-cytotoxic t-lymphocyte protein 4 [CTLA4] therapy such as ipilimumab, or other experimental immune checkpoint pathway inhibitors administered in a clinical trial)
• Leukocytes >= 3,000/mcL
• Hemoglobin >= 9 g/dL
• Neutrophil count >= 1,500/mcL

You may not qualify if…

• Life expectancy < 6 weeks by investigator assessment
• Other active malignancy requiring treatment, except for cutaneous malignancies that require resection such as squamous cell carcinoma, basal cell carcinoma, or cutaneous melanoma, and except for prostate cancer if only on androgen deprivation therapy
• Significant peripheral neuropathy (grade 2 or higher by Common Terminology Criteria for Adverse Events [CTCAE])
• Sensorineural hearing loss (grade 2 or higher by CTCAE)
• Must NOT have had prior treatment with ATR inhibitor (prior BAY1895344 or other investigational ATR inhibitors), or current treatment with any other investigational agents
• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study. Patients who have targeted therapies (such as PARP inhibitors) within 2 weeks prior to entering the study
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to BAY 1895344 or other agents used in study
• Patients receiving any medications that are substrates of CYP3A4 with a narrow therapeutic window, or strong inhibitors/inducers of CYP3A4 are ineligible, if they cannot be transferred to alternative medication. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• Patients with uncontrolled intercurrent illness
• Patients with psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because BAY 1895344 as a DNA-damage response inhibitor, cisplatin, and gemcitabine may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with BAY 1895344 breastfeeding should be discontinued if the mother is treated with BAY 1895344 and for 4 months after end of treatment. These potential risks may also apply to other agents used in this study

Where it is running

• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States
• National Cancer Institute Developmental Therapeutics Clinic — Bethesda, Maryland, United States
• National Institutes of Health Clinical Center — Bethesda, Maryland, United States
• NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center — New York, New York, United States
• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States
• UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States
• University of Wisconsin Carbone Cancer Center - University Hospital — Madison, Wisconsin, United States
• University Health Network-Princess Margaret Hospital — Toronto, Ontario, Canada

Full record on ClinicalTrials.gov

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