RP-3467 + Olaparib for Cancer

(POLAR Trial)

Not currently recruiting at 10 trial locations

Overseen By Repare Clinical Representative

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Repare Therapeutics

Disqualifiers: Brain metastases, Active cancers, MDS, AML, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 20 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, RP-3467 (experimental treatment), alone or with another drug, Olaparib (also known as Lynparza), to evaluate their safety and effectiveness in treating certain advanced cancers. It focuses on cancers that have not responded to standard treatments, such as advanced ovarian, breast, prostate, or pancreatic cancer. Suitable candidates for this trial have one of these cancers and have not benefited from previous treatments. As a Phase 1 trial, participants may be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that RP-3467, when tested alone, was safe and well-tolerated in earlier studies. Participants generally handled the treatment well, with no major safety concerns reported. Olaparib, a drug often used to treat certain types of cancer, also has a strong safety record. It is generally considered safe, though some patients may experience side effects like nausea or tiredness.

When RP-3467 and olaparib are used together, studies aim to determine if they remain safe. As this is an early-phase trial, the main goal is to assess how well participants handle the treatments. Data on safety is still being collected. However, findings so far are promising for both treatments, whether used alone or together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about RP-3467 and its combination with Olaparib because these treatments offer a fresh approach to tackling cancer. Most traditional cancer treatments, like chemotherapy, target rapidly dividing cells, but RP-3467 works differently by enhancing the body's natural immune response to attack cancer cells. When combined with Olaparib, a PARP inhibitor that prevents cancer cells from repairing themselves, the treatment aims to produce a more potent anti-cancer effect. This dual mechanism of boosting the immune system while blocking cancer cell repair sets these treatments apart from existing options and holds promise for more effective outcomes.

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

Research has shown that olaparib effectively treats ovarian cancer, particularly in individuals with BRCA mutations. This drug prevents cancer cells from repairing themselves, slowing tumor growth. RP-3467 is a newer treatment, and early studies suggest it might improve outcomes and reduce side effects when combined with other treatments. In this trial, participants will join different treatment arms: one group will receive RP-3467 monotherapy, while another will receive a combination of RP-3467 and olaparib. Researchers are examining whether the combination works better for treating advanced solid tumors. Although these findings are promising, further research is needed to confirm the effects. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have specific molecular characteristics. Participants must meet certain health standards and not be receiving other cancer treatments.

Inclusion Criteria

I can provide a sample of my tumor, either from previous tests or a new biopsy.

My organs are functioning well.

My blood test results are within normal ranges.

Exclusion Criteria

I have brain metastases that are not well-managed and cause symptoms.

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

I have been treated with a Polθ inhibitor that is not RP-3467.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive RP-3467 alone or in combination with Olaparib with dose escalation to determine MTD or MAD

20 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib
• RP-3467

Trial Overview The study tests the safety and effects of RP-3467, a new potential cancer drug, both alone and combined with Olaparib, an existing treatment. It's to see how these drugs work in patients with advanced tumors.

How Is the Trial Designed?

Group I: Arm2: RP-3467 + Olaparib combination Experimental Treatment 2 Interventions

Eligible participants will be treated with escalating doses of RP-3467 in combination with Olaparib

Group II: Arm 1: RP-3467 monotherapy Experimental Treatment 1 Intervention

Eligible participants will be treated with escalating doses of RP-3467 monotherapy

Olaparib is already approved in European Union, United States for the following indications:

Approved in European Union as Lynparza for:

• Breast cancer
• Ovarian cancer
• Fallopian tube cancer
• Peritoneal cancer
• Pancreatic cancer
• Prostate cancer
• Endometrial cancer

Approved in United States as Lynparza for:

• Ovarian, fallopian tube, and primary peritoneal cancer
• Breast cancer
• Prostate cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Repare Therapeutics

Lead Sponsor

Trials

10

Recruited

1,300+

Published Research Related to This Trial

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]

Olaparib is an oral medication that inhibits poly (ADP-ribose) polymerase and is primarily developed for treating BRCA mutation-positive ovarian cancer, with its capsule formulation already approved in the EU and USA.

The drug is currently undergoing extensive clinical trials for various cancers, including breast, gastric, and pancreatic cancers, indicating its potential broad application in oncology beyond ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: first global approval. Deeks, ED.[2020]

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]

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 (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, 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 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 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]

Citations

1. ir.reparerx.com ir.reparerx.com/news-releases/news-release-details/repare-therapeutics-doses-first-patient-phase-1-clinical-trial-2

Repare Therapeutics Doses First Patient in Phase 1 ... “In addition, Repare's previously reported data established the potential for RP-3467 to improve efficacy and limit toxicity in combination ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06560632

NCT06560632 | Phase 1 Trial of RP-3467 Alone and in ... The DMC can recommend to the sponsor that the trial be stopped if it is not effective, is harming participants, or is unlikely to serve its scientific purpose.

3. clinicaltrialsarena.com clinicaltrialsarena.com/news/repare-solid-tumour-trial-2/

Repare doses first subject in Phase I solid tumour ... “In addition, Repare's previously reported data established the potential for RP-3467 to improve efficacy and limit toxicity in combination ...

4. clin.larvol.com clin.larvol.com/trial-detail/NCT06560632

Phase 1 Trial of RP-3467 Alone and in Combination With ... Upcoming expected milestone: Q4 2025: Topline safety, tolerability and early efficacy data from the POLAR trial in monotherapy and in combination with olaparib.

5. withpower.com withpower.com/trial/rp-3467-olaparib-for-cancer-33d02

RP-3467 + Olaparib for Cancer (POLAR Trial) Olaparib has shown effectiveness in treating ovarian cancer, particularly in patients with BRCA mutations, by helping to prevent cancer cells from repairing ...

6. crisprmedicinenews.com crisprmedicinenews.com/press-release-service/card/repare-therapeutics-announces-updated-positive-safety-and-tolerability-results-from-the-phase-1-myth/

Repare Therapeutics Announces Updated Positive Safety ... Repare Therapeutics Announces Updated Positive Safety and Tolerability Results from the Phase 1 MYTHIC Clinical Trial. Oct. 23, 2024. Data ...