Study of a New InvestigationaI Inhibitor to Treat People with Advanced Solid Tumors

About the Study

The study will test if an investigational treatment, XL309, is safe and works when used alone or in combination with a PARP inhibitor to treat people with some advanced solid tumors. The study is looking to enroll adults with certain types of cancer, including those with:

• BRCA1 or BRCA2 mutations (HER2-negative breast cancer, prostate cancer and pancreatic cancer);
• high-grade ovarian, fallopian tube or primary peritoneal cancer; or
• other solid tumors with certain genetic mutations.

XL309 is an inhibitor that blocks an enzyme called USP1. Blocking USP1 in cancer cells may prevent tumors from repairing their damaged DNA, causing the cancer cells to die.

Some people in the study will be treated with XL309 in combination with olaparib. Olaparib is an inhibitor that blocks an enzyme called PARP. Olaparib is approved to treat certain cancers, including some forms of breast cancer, ovarian cancer, pancreatic cancer and prostate cancer.

The use of XL309, alone or in combination with olaparib, is being investigated in this clinical trial and has not been approved by the FDA. Safety and efficacy have not been established and are being studied as part of this trial.

What the Study Involves

This is a phase 1, open-label study, which means if you take part in the study, you and your doctor will know which drug(s) are being given. The study will be run in two different parts:

• Part 1 will focus on learning about the safety of the study drug (XL309) and how the study drug works at different doses.  
• Part 2 will focus on how the study treatments (XL309 alone or in combination with olaparib) affect the human body and if the treatments work to treat cancer.

If you are eligible and decide to take part in the XL309 study:

• You may receive the investigational treatment (XL309) alone or in combination with the PARP inhibitor (olaparib).
• The dose and combination of study drugs will depend on your cancer type and when you enroll in the study.
  • XL309 is taken by mouth, once a day.
  • Olaparib is taken by mouth, twice a day.
• You will be in the study for about 4 to 6 months. The length of time you are on the study can depend on how your cancer responds to the treatment, and if you have any side effects. You or your doctor can choose to stop the study treatment at any time.
• You will visit the doctor for:
  • lab tests and physical exams (about every 1-4 weeks)
  • scans (about every 8 weeks)  

The time between visits will depend on which part of the study you join.

• You will return 28 days after your final dose for a follow-up visit.

Talk to your doctor to learn more about this study and if it may be an option for you.

People may be eligible who: 

• Are aged 18 years or older
• Have locally advanced or metastatic:
• High-grade serous ovarian cancer (including primary peritoneal cancer and fallopian tube cancer)
• HER2-negative breast cancer with a BRCA1 or BRCA2 mutation or acquired BRCA1 or BRCA2 tumor mutation
  (somatic mutation)
• Castration-resistant prostate cancer with a BRCA1 or BRCA2 mutation or acquired BRCA1 or BRCA2 tumor mutation (somatic mutation)
• Pancreatic cancer with a BRCA1 or BRCA2 mutation or acquired BRCA1 or BRCA2 tumor mutation (somatic mutation)
• Other solid tumors with a homologous recombination repair (HRR) mutation or homologous recombination deficiency
  (HRD)
• Have cancer that continued to grow after prior treatment, or who had to stop prior treatment due to side effects or who have no other approved treatment options.

Note: If you had treatment with a PARP inhibitor before, you may be eligible for the study. Talk to the study doctor about how your body tolerated prior PARP inhibitor therapy to see if you are eligible for this study treatment.

There are other requirements to participate in this study. The study doctor will help determine if this study is right for you.

People may not be eligible who:

• Had prior treatment with a USP1 inhibitor
• Have certain heart conditions
• Have other medical conditions that may affect their ability to participate in the study

There are other requirements to participate in this study. The study doctor will help determine if this study is right for you.