Treating Advanced Cancers with BRCA or Other Related Gene Mutations Using Targeted Therapy MOMA-313 Alone or In Combination with the PARP Inhibitor Olaparib

About the Study

This trial will study an investigational drug called MOMA-313 given alone or together with a PARP inhibitor (olaparib). MOMA-313 is a targeted therapy that blocks the activity of an enzyme called “DNA polymerase theta.” People with certain advanced or metastatic cancers with any of the following mutations may be eligible for this trial: ATM, BRCA1, BRCA2, BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, and/or RAD54L mutations. The eligible mutations may depend on the stage of the study. The trial aims to understand MOMA-313 safety, tolerability, initial effectiveness, and how the drug moves through and affects the body.

What the Study Involves

This is a phase 1 trial that will study whether it is safe for participants with certain advanced or metastatic cancers to take a drug called “MOMA‑313” by itself or together with another drug called “olaparib”. Both MOMA-313 and olaparib will be administered orally.

Participants will be enrolled into one of two groups, depending on when they join the study.

• Group 1: The trial will begin by giving MOMA-313 by itself to a group of participants. If researchers determine that this dose is safe, another group of participants in this group will receive a higher dose of MOMA-313 by itself. This process of increasing the dose will continue until unacceptable side effects occur, or until it is clear that further dose increases will not be helpful.
• Group 2: After MOMA-313 has been deemed safe in Group 1, recruitment will begin for Group 2. This group will receive MOMA-313 and olaparib together. Group 2 will use the same process of increasing the dose as used for Group 1.

Once a dose is determined safe and acceptable in either arm of the study, additional participants may be enrolled to further confirm the safety, tolerability, and effectiveness of the dose, as well as to confirm the acceptability of the dose for future studies.

The study involves the following study periods and visits.

• A screening period to determine your eligibility in the study.
• A treatment period where you will receive your study treatment and be carefully monitored for safety and your cancer. There is no defined maximum length of treatment. As long as the study remains open, participants may continue treatment for as long as they want, unless their physicians or researchers determine that they should stop (for example, if they determine it is not safe or beneficial to continue treatment).
• An end of treatment visit and safety follow-up visit to evaluate your health once you have completed study treatment. End of treatment is usually conducted within 5 days from your last dose of study treatment and the safety follow-up visit is performed within 28 days from the end of treatment visit. 
• A long-term follow-up phone call every 3 months to assess status.

Study procedures will include blood samples, vital signs, physical examinations, cardiac monitoring, scans to evaluate the extent of disease, and daily dosing diary completion. Tumor biopsy samples will also be obtained but this is optional.  

Reimbursement is being offered to participants, which may include travel, lodging, and meals.

This trial will include adult participants (18 years or older) with cancer who have solid tumors that are “advanced” (large, complex, or aggressive) or “metastatic” (have spread to other parts of the body). Some requirements for participation include the following:

• You must have a specific gene mutation in your tumor that affects the ability of cells to repair DNA damage in a process called homologous recombination (HR). The HR-deficiency alterations that may qualify you for inclusion into the study are: ATM, BRCA1, BRCA2, BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, and/or RAD54L mutations. The eligible HR-deficiency alterations may depend on the stage of the study.
• You may be eligible for this study if you have had previous treatment with a PARP inhibitor or have not had previous treatment with a PARP inhibitor. In one part of the study, you must not have received a PARP inhibitor to be considered for the study.
• You must be fully recovered from effects of prior therapy, radiotherapy, and/or surgery.
• You must not be pregnant or breastfeeding.

Some exclusions into this trial include the following:

• You have a severe or uncontrolled systemic disease or infection.
• You have active liver disease or known HIV/AIDS-related illness (there are some exceptions).
• You have an active prior or ongoing cancer (there are some exceptions).
• You have impaired gastrointestinal function.
• You are receiving other systemic anticancer therapies.
• You have a known hypersensitivity to PARP inhibitors (only if you are being considered for the combination arm with MOMA-313 and olaparib).