MOMA-313 + Olaparib for Solid Tumors

Recruiting at 23 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 trial explores the safety and tolerability of the new treatment MOMA-313, both alone and combined with Olaparib, a targeted cancer therapy, in individuals with certain solid tumors. The trial aims to determine the optimal dose and understand how the body processes these treatments. It seeks participants with advanced or metastatic solid tumors that cannot be cured, particularly those with HR-deficient mutations. Individuals with severe forms of cancer, such as prostate, breast, or pancreatic cancer, who have not tried similar treatments, may find this trial suitable. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have tested MOMA-313 in patients with certain advanced solid tumors. These studies assessed the treatment's safety and patient tolerance. Researchers found that MOMA-313 is generally well-tolerated, with manageable side effects.

When combined with olaparib, studies have shown that safety remains consistent, even for patients with extensive prior treatments. The FDA has already approved olaparib for other uses, indicating its general safety when used correctly.

This trial is in its early stages, aiming to evaluate the safety of these treatments and determine the best dose. Due to its early phase, information on long-term safety may be limited. However, the focus on safety and patient tolerance is a positive sign. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for solid tumors, which often involve chemotherapy or radiation, MOMA-313 is a novel therapy that targets cancer cells directly. Researchers are particularly excited about MOMA-313 in combination with olaparib because this duo could enhance the effectiveness of treatment by not only interfering with the cancer cells' DNA repair mechanisms but also amplifying the impact of each drug when used together. MOMA-313 as a monotherapy offers a unique approach by acting as a single-agent treatment, potentially reducing the side effects associated with combination therapies. This innovative strategy opens up new possibilities for treating solid tumors more effectively and with potentially fewer side effects.

What evidence suggests that this trial's treatments could be effective for homologous recombinant deficient solid tumors?

Research shows that MOMA-313 is a promising treatment for solid tumors with a genetic issue known as homologous recombination deficiency (HR-deficient). Studies have found that MOMA-313, which blocks a protein called Polθ, can shrink tumors in lab models of BRCA-deficient cancers, a type of HR-deficient cancer. In this trial, one group of participants will receive MOMA-313 as a monotherapy, while another group will test the combination of MOMA-313 with Olaparib, a drug effective against certain cancers. Early results suggest that this combination can lead to better outcomes for patients with HR-deficient tumors. Although more data is needed, this combination therapy targets weaknesses in cancer cells, making it a promising option. ^{1 2 6 7 8}

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

My organs are working well according to recent tests.

Written informed consent obtained according to local guidelines

Histologically confirmed disease for each treatment arm as follows:

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, 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]

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]

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]

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]

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]

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]

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. momatx.com momatx.com/wp-content/uploads/2024/10/2024-MOMA-313-poster-EORTC-NCI-AACR-_final.pdf

MOMA-313 is a potent, selective Polθ inhibitor that ... • MOMA-313 displays dose-dependent efficacy and drives tumor regressions in combination with olaparib against multiple BRCA-deficient PDX models in ...

2. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT06545942

UCSF Solid Tumor Trial → Orally Administered MOMA-313 in ... The data from this study conducted in patients with HR-deficient advanced or metastatic solid tumors, including safety, tolerability, PK/PDx findings, and ...

3. trialx.com trialx.com/clinical-trials/listings/297690/study-of-orally-administered-moma-313-in-participants-with-advanced-or-metastatic-solid-tumors/

Study of Orally Administered MOMA-313 in Participants ... The data from this study conducted in patients with HR-deficient advanced or metastatic solid tumors, including safety, tolerability, PK/PDx ...

4. clinicaltrialsarena.com clinicaltrialsarena.com/news/moma-patient-trial-moma-313/

MOMA Therapeutics doses first patient in trial of cancer drug The multi-centre, open-label study aims to evaluate MOMA-313's safety and tolerability in patients with solid tumours. Go deeper with ...

5. npcf.us npcf.us/clinical-trials/study-of-orally-administered-moma-313-in-participants-with-advanced-or-metastatic-solid-tumors/

Study Of Orally Administered MOMA-313 In Participants ... The data from this study conducted in patients with HR-deficient advanced or metastatic solid tumors, including safety, tolerability, PK/PDx findings, and ...

6. urologytimes.com urologytimes.com/view/study-launches-of-moma-313-in-solid-tumors-including-prostate-cancer

Study launches of MOMA-313 in solid tumors, including ... The phase 1 trial is assessing the safety and tolerability of MOMA-313 as both a monotherapy and in combination with olaparib in patients with HR-deficient ...

7. facingourrisk.org facingourrisk.org/research-clinical-trials/study/328/treating-advanced-cancers-with-dna-repair-mutations-using-moma-313-alone-or-in-combination-with-the-parp-inhibitor-olaparib

Treating Advanced Cancers with DNA-Repair Mutations ... This trial will study the safety, tolerability, and initial effectiveness of MOMA-313, a new type of targeted therapy, alone or in combination with the PARP ...

8. momatx.com momatx.com/posts/moma-therapeutics-announces-initiation-of-phase-1-clinical-trial-for-moma-313/

MOMA Therapeutics Announces Initiation of Phase 1 ... The Phase 1 trial (NCT06545942) is a multi-center, open-label study designed to evaluate the safety and tolerability of MOMA-313 as monotherapy ...