Olaparib for Advanced Cancer

Recruiting at 135 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Colony-stimulating factors, PARP inhibitors

Disqualifiers: Active malignancy, CNS metastases, HIV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 53 months

390 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received any anti-cancer treatments like chemotherapy, biological therapy, or targeted therapy within 3 weeks before starting the study. It's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug Olaparib (Lynparza) for advanced cancer?

Olaparib (Lynparza) has shown effectiveness in treating ovarian cancer, particularly in patients with BRCA mutations, by demonstrating antitumor activity and improving progression-free survival (the time during which the cancer does not get worse). It is also approved for use in high-risk early breast cancer with BRCA mutations, indicating its potential effectiveness in other advanced cancers with similar genetic profiles. ^{1 2 3 4 5}

Is Olaparib (Lynparza) safe for humans?

Olaparib (Lynparza) has been studied for safety in various cancers, including breast and ovarian cancer. It generally has a manageable safety profile, meaning that while there may be side effects, they are typically not severe and can be managed with medical care. ^{1 2 6 7 8}

What makes the drug Olaparib unique for treating advanced cancer?

Olaparib is unique because it is a PARP inhibitor (a type of drug that blocks an enzyme involved in repairing damaged DNA) and is used specifically for cancers with BRCA mutations, which are often resistant to other treatments. It is taken orally and has shown effectiveness in treating various cancers, including ovarian and breast cancer, by targeting tumors with faulty DNA repair mechanisms. ^{1 2 3 4 8}

What is the purpose of this trial?

This study will evaluate the efficacy and safety of olaparib (MK-7339) monotherapy in participants with multiple types of advanced cancer (unresectable and/or metastatic) that: 1) have progressed or been intolerant to standard of care therapy; and 2) are positive for homologous recombination repair mutation (HRRm) or homologous recombination deficiency (HRD).

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with advanced cancers that have worsened after standard care or if they're intolerant to it. They must have specific genetic changes (HRRm/HRD positive) and be able to provide a biopsy. Participants need a life expectancy of at least 3 months, good organ function, and an ECOG status of 0 or 1. Men must use contraception; women not pregnant/breastfeeding should also use effective birth control.

Inclusion Criteria

My advanced cancer has no cure and standard treatments have failed.

My breast cancer is due to a BRCA mutation.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have been diagnosed with MDS, AML, or conditions that suggest I might have them.

You are allergic to the ingredients in olaparib.

I have an active hepatitis infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral olaparib, 300 mg twice daily (BID) for advanced cancer treatment

Up to 53 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Olaparib

Trial Overview The study tests Olaparib's effectiveness and safety in treating various advanced cancers with certain genetic mutations (HRRm/HRD). Patients previously treated without success are given this medication as monotherapy to see how well it works against their cancer.

Participant Groups

Group I: Olaparib Experimental Treatment 1 Intervention

Participants with HRRm or HRD-positive advanced cancer will receive oral olaparib, 300 mg twice daily (BID).

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?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

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 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]

The OPINION study is evaluating the safety and efficacy of olaparib as a maintenance therapy for women with high-grade serous or endometrioid platinum-sensitive relapsed ovarian cancer who do not have BRCA mutations, involving patients who have undergone at least two prior lines of platinum-based chemotherapy.

The primary goal of the study is to assess progression-free survival, which will help determine how effective olaparib is in delaying cancer progression in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. Poveda, AM., Davidson, R., Blakeley, C., 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, a PARP inhibitor, has shown significant clinical benefits in improving progression-free survival for patients with BRCA1 or BRCA2 mutated HER2 negative metastatic breast cancer compared to standard chemotherapy.

The drug has a manageable safety profile, making it a promising treatment option, particularly for triple negative breast cancer, although further research is needed to optimize its use with other therapies and identify suitable biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of breast cancer. Griguolo, G., Dieci, MV., Guarneri, V., et al.[2019]

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]

References

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

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

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

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

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

Olaparib: first global approval. [2020]

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

Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. [2020]

6. Germany pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of breast cancer. [2019]

8. England pubmed.ncbi.nlm.nih.gov

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