Testing the Targeted Therapy Elimusertib in Combination with Chemotherapy for Advanced Cancers

About the Study

This study is how well the drug elimusertib (a type of targeted therapy known as an ATR inhibitor) works when combined with chemotherapy for treating people with advanced cancers, including urothelial, ovarian, gastric, endometrial, triple-negative breast cancer and others.

What the Study Involves

There will be two groups in this study. All participants will receive the study drug elimusertib. People will be assigned to a group based on their cancer type. 

Group 1: Ovarian, endometrial, triple-negative breast, urothelial, gastric, biliary tract, lung, head and neck

• Participants will receive the chemotherapy drug cisplatin intravenously over 1-2 hours on day 1 and 8. 
• Participants will take elimusertib orally once daily on days 2 and 9. Treatment repeats every 21 days for up to 6 cycles as long as the cancer doesn’t get worse and there are no unacceptable side effects. 

Group 2: Urothelial cancers only

• Participants will receive cisplatin intravenously over 1-2 hours on day 1 and 8, gemcitabine intravenously over 20 minutes on days 1 and 8, and elimusertib orally once daily on days 2 and 9. Treatment repeats every 21 days for up to 6 cycles as long as there is no disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up to 30 days, then every 3 months thereafter.

Study Sites:

California

• Sacramento
  University of California Davis Comprehensive Cancer Center
  Contact Person: Dr. Mamta Parikh at 916-734-3089

Maryland

• Bethesda
  National Cancer Institute Developmental Therapeutics Clinic 
  Contact Person: Dr. Naoko Takebe at 800-411-1222

New York

• New York
  NYP/ Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
  Contact Person: Dr. Mark Stein at [email protected]

Ohio

• Columbus
  Ohio State University Comprehensive Cancer Center
  Contact Person: Dr. Ming Yin at  [email protected] or 800-293-5066

Pennsylvania

• Pittsburgh
  University of Pittsburgh Cancer Institute
  Contact Person: Dr. Leonard Appleman at 412-647-8073 

Wisconsin

• Madison
  University of Wisconsin Carbone Cancer Center
  Contact Person: Dr. Hamid Emamekhoo at 800-622-8922

Ontario, Canada

• Toronto
  University Health Network-Princess Margaret Hospital
  Contact 416-946-4501 or [email protected]  

People 18 years and older who meet the following criteria:

• Advanced solid tumor for which cisplatin-based therapy would be appropriate, including:
  • Urothelial cancer
  • Penile cancer
  • Esophageal and gastric cancers
  • Ovarian cancer
  • Endometrial cancer
  • Cervical cancer
  • Triple negative breast cancer
• For the second arm of the study
  • Participants with advanced or unresectable urothelial cancer
• Participants with prior cisplatin treatment must have received the last treatment at least 6 months prior to enrollment
• Prior treatment with PARP inhibitors and/or immune checkpoint inhibitor therapy is permitted
• People with HIV, Hepatitis B or Hepatitis C must be undectable
• Participants with brain metastases or leptomeningeal disease are eligible if:
  • follow-up brain imaging of treated brain metastases after therapy shows no evidence of cancer getting worse.
  • immediate brain or nervous system treatment is not required and unlikely to be during the first cycle of therapy
  • participants with stable brain metastases that have no symptoms
• Participants with known history or current symptoms of cardiac disease, or history of treatment with drugs that damage the heart need to be checked to make sure their heart function is ok 

• Life expectancy of less than 6 weeks
• Other cancer diagnoses requiring treatment, except for certain types of skin cancer or prostate cancer (if only on androgen deprivation therapy)
• Significant peripheral neuropathy (weakness, numbness, and pain in the hands and feet due to nerve damage) 
• Hearing loss
• Must NOT have had prior treatment with ATR inhibitor or current treatment with any other investigational agents
• Participants who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study. Participants who have had targeted therapies (such as PARP inhibitors) within 2 weeks prior to entering the study
• Participants with any additional current uncontrolled illness
• Participants with psychiatric illness/social situations that would limit the ability to follow study requirements
• Pregnant people (breastfeeding should be discontinued if the mother is treated with the anti-cancer drug BAY 1895344 and for 4 months after end of treatment)