MOMA-313 + Olaparib for Solid Tumors

Recruiting at 19 trial locations

Overseen By MOMA Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: MOMA Therapeutics

Must be taking: PARP inhibitors

Must not be taking: Polymerase theta inhibitors

Disqualifiers: Cardiovascular disease, CNS metastasis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 21-28 day cycles

158 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This Phase 1, multi-center, open-label, dose escalation and dose optimization study is designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PDx), and preliminary clinical activity of MOMA-313 administered orally as a single agent or combination therapy in patients with homologous recombinant deficient solid tumors.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you must be fully recovered from the effects of prior therapy, and hormonal therapy is allowed. It's best to discuss your specific medications with the trial team.

What safety data exists for Olaparib (Lynparza) in humans?

Olaparib (Lynparza) has been studied for safety in various trials, including in Japanese and Chinese patients with advanced solid tumors, and in patients with breast or ovarian cancer. These studies generally show that Olaparib can be administered safely, though like many medications, it may have side effects. ^{1 2 3 4 5}

What makes the drug MOMA-313 + Olaparib unique for treating solid tumors?

The combination of MOMA-313 with Olaparib is unique because Olaparib is a PARP inhibitor that has shown effectiveness in treating cancers with specific genetic mutations, like BRCA mutations, by targeting cancer cells' DNA repair mechanisms. This combination may offer a novel approach for solid tumors, potentially enhancing the effectiveness of treatment by combining different mechanisms of action. ^{2 3 6 7 8}

What data supports the effectiveness of the drug Olaparib in treating solid tumors?

Olaparib, a drug used for certain types of breast and ovarian cancer, has shown effectiveness in patients with specific genetic mutations that affect DNA repair. It is particularly beneficial for those with BRCA mutations, and research suggests it may also help patients with other DNA repair issues. ^{2 3 6 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic solid tumors, such as pancreatic, prostate, ovarian, and breast cancers. Participants must have a deficiency in homologous recombination repair mechanisms within their tumor cells.

Inclusion Criteria

Histologically confirmed disease for each treatment arm as follows:

My organs are working well according to recent tests.

Written informed consent obtained according to local guidelines

Exclusion Criteria

I have been treated with a polymerase theta inhibitor before.

Undetectable viral load or CD4+ count ≥300 cells/μL

I don't have any health issues that could risk my safety or affect the study results.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MOMA-313 as a single agent or in combination with olaparib in dose-escalation and dose-optimization phases

21-28 day cycles

Multiple visits per cycle

Follow-up

Participants are monitored for safety, tolerability, and clinical activity after treatment

Up to 35 months

What Are the Treatments Tested in This Trial?

Interventions

• MOMA-313
• Olaparib

Trial Overview The study tests the safety and effects of MOMA-313 taken by mouth alone or combined with Olaparib. It's an early-phase trial to find the right dose and see how these drugs affect participants' bodies (PK/PDx) and their cancer.

How Is the Trial Designed?

Group I: MOMA-313 in Combination with Olaparib (Treatment Arm 2) Experimental Treatment 2 Interventions

MOMA-313 administered together with twice daily (BID) olaparib in 28-day cycles.

Group II: MOMA-313 Monotherapy (Treatment Arm 1) Experimental Treatment 1 Intervention

MOMA-313 administered as a single-agent in 21-day cycles.

Who Is Running the Clinical Trial?

MOMA Therapeutics

Lead Sponsor

Trials

1

Recruited

160+

Published Research Related to This Trial

Olaparib (Lynparza) is approved for treating adult patients with high-risk early breast cancer that has a germline BRCA mutation, following chemotherapy treatment.

This approval highlights Olaparib's role as an adjuvant therapy, which means it is used after initial treatments to help prevent cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Treatment for High-Risk Early Breast Cancer. Aschenbrenner, DS.[2022]

Olaparib is particularly effective for patients with BRCA-mutated ovarian cancer, but it also benefits a subset of patients with BRCA wild-type tumors that have loss-of-function mutations in DNA repair genes, showing similar treatment outcomes.

The study suggests that patients with specific HRR gene mutations, even without BRCA mutations, can be identified as a group that may respond well to olaparib, indicating a potential for broader use of this treatment in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. Hodgson, DR., Dougherty, BA., Lai, Z., et al.[2020]

Olaparib, a PARP inhibitor, showed a 36% objective response rate in women with relapsed ovarian cancer and a germline BRCA1/2 mutation, even after they had undergone multiple lines of chemotherapy, indicating its efficacy in this challenging patient population.

The median duration of response to olaparib was 7.4 months, and the safety profile was consistent across patients who had received three or more lines of prior chemotherapy, with similar rates of serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Matulonis, UA., Penson, RT., Domchek, SM., et al.[2022]

Olaparib is a powerful inhibitor of PARP-1 and PARP-2, showing effectiveness in treating ovarian cancer, particularly in patients with germline BRCA mutations.

Phase III trials are currently evaluating olaparib's efficacy as a maintenance therapy after initial treatment in patients with BRCA mutations, highlighting its potential role in long-term cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer. Gunderson, CC., Moore, KN.[2016]

Olaparib is an effective oral treatment for patients with BRCA mutation-positive ovarian cancer, approved for maintenance therapy after platinum-based chemotherapy, showing good tolerability with common side effects like nausea, fatigue, and anemia being mild to moderate.

Long-term monitoring is recommended due to a low risk of serious hematological complications, such as anemia and myelodysplastic syndrome, ensuring patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. Lheureux, S., Bowering, V., Karakasis, K., et al.[2015]

The combination of olaparib and carboplatin was found to be safe and effective in treating breast and ovarian cancer in patients with germline BRCA1 or BRCA2 mutations, with 50% of patients showing a partial response and one patient achieving a complete response.

Proteomic analysis indicated that high levels of FOXO3a expression before treatment may predict a better response to the therapy, suggesting a potential biomarker for future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses. Lee, JM., Hays, JL., Annunziata, CM., et al.[2022]

In a Phase I study involving 28 Japanese patients with advanced solid tumors, olaparib tablets at doses of 200 and 300 mg twice daily were found to be tolerable, with no dose-limiting toxicities reported.

The most common side effects included nausea, decreased appetite, anemia, and constipation, but no confirmed antitumor responses were observed, leading to the selection of 300 mg bid as the recommended dose for future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of the olaparib tablet formulation in Japanese patients with advanced solid tumours. Yonemori, K., Tamura, K., Kodaira, M., et al.[2022]

The pharmacokinetic (PK) profile of olaparib in Chinese patients with advanced solid tumors is similar to that observed in Western and Japanese populations, confirming that the recommended dose of 300 mg twice daily is appropriate for this group.

When olaparib was combined with paclitaxel, there was a significant decrease in olaparib exposure, and while adverse events were rare, hematological side effects were more common in patients receiving the combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of olaparib tablets as monotherapy and in combination with paclitaxel: results of a Phase I study in Chinese patients with advanced solid tumours. Yuan, P., Shentu, J., Xu, J., et al.[2020]

Olaparib is an effective treatment for patients with platinum-sensitive, relapsed BRCA-mutated high-grade serous ovarian cancer, showing significant improvement in progression-free survival compared to placebo in a study of 265 patients.

The treatment is generally well tolerated, with most side effects being mild to moderate, although fatigue, anemia, and neutropenia were noted as more severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: a review of its use as maintenance therapy in patients with ovarian cancer. Frampton, JE.[2016]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

New Adjuvant Treatment for High-Risk Early Breast Cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer. [2016]

5. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Safety and tolerability of the olaparib tablet formulation in Japanese patients with advanced solid tumours. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of olaparib tablets as monotherapy and in combination with paclitaxel: results of a Phase I study in Chinese patients with advanced solid tumours. [2020]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Olaparib: a review of its use as maintenance therapy in patients with ovarian cancer. [2016]