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
A Phase 1 Trial of the ATR Inhibitor BAY 1895344 in Combination With Cisplatin and With Cisplatin Plus Gemcitabine in Advanced Solid Tumors With an Emphasis on Urothelial Carcinoma
4 other identifiers
interventional
74
2 countries
8
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Aug 2021
Longer than P75 for phase_1
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 29, 2020
CompletedFirst Posted
Study publicly available on registry
July 30, 2020
CompletedStudy Start
First participant enrolled
August 25, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2026
April 13, 2026
December 1, 2025
4.8 years
July 29, 2020
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of adverse events
Toxicities will be tabulated and reported according to dose level, grade, type, cycle, and attribution. Tables will be created to summarize these toxicities and side effects, overall and by cohort. Proportions and associated 95% confidence intervals will be calculated for each cohort separately. Cumulative incidence curves will be used to estimate the proportion of patients who will discontinue therapy for reasons of toxicity or general inability to tolerate the regimen.
Up to 28 days after completion of study treatment
Recommended phase 2 dose (RP2D) of BAY 1895344
Up to 21 days from treatment start date
Secondary Outcomes (5)
Pharmacokinetic (PK) parameter - maximum concentration (Cmax)
Day 2 and day 9 after treatment start date
PK parameter - area under the concentration-time curve (AUC)
Day 2 and day 9 after treatment start date
Deoxyribonucleic acid (DNA) damage repair (DDR) mutations
Up to 2 years
Response rate
Up to 2 years
Progression-free survival (PFS)
Up to 2 years
Study Arms (2)
Arm I (cisplatin, elimusertib)
EXPERIMENTALPatients receive cisplatin IV over 1-2 hours on day 1 and 8, and elimusertib PO QD 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 (cisplatin, gemcitabine, elimusertib)
EXPERIMENTALPatients receive cisplatin IV over 1-2 hours on day 1 and 8, gemcitabine IV over 30 minutes on days 1 and 8, and elimusertib PO QD on days 2 and 9. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given PO
Given IV
Eligibility Criteria
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)
- 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)
- +21 more criteria
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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (8)
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
National Cancer Institute Developmental Therapeutics Clinic
Bethesda, Maryland, 20892, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Mamta Parikh
City of Hope Comprehensive Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 29, 2020
First Posted
July 30, 2020
Study Start
August 25, 2021
Primary Completion (Estimated)
June 30, 2026
Study Completion (Estimated)
June 30, 2026
Last Updated
April 13, 2026
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.