Tremelimumab + Olaparib for Recurrent Ovarian Cancer

Recruiting at 21 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, CYP3A4 inhibitors

Disqualifiers: Active infection, Liver disease, Autoimmune, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

61 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase II trial studies how well olaparib with or without tremelimumab works in treating patients with ovarian, fallopian tube, or peritoneal cancer that has come back (recurrent). PARPs are proteins that help repair deoxyribonucleic acid (DNA) mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Immunotherapy with monoclonal antibodies, such as tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving olaparib and tremelimumab together may work better than olaparib alone in treating patients with ovarian, fallopian tube, or peritoneal cancer.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, hormonal therapy for cancer must be stopped at least 28 days before enrollment, and any other cancer treatments, including chemotherapy and radiation, must also be stopped at least 28 days prior. If you are on potent CYP3A4 inhibitors or inducers, these must be discontinued before starting treatment.

What safety data exists for the treatment of Tremelimumab + Olaparib in humans?

Olaparib, also known as Lynparza, has been tested in various trials for ovarian cancer and is generally considered safe, but it can cause side effects like nausea, fatigue, and anemia (low red blood cell count). Serious conditions like myelodysplastic syndrome (a blood disorder) and acute myeloid leukemia (a type of blood cancer) occurred in a small percentage of patients. There is no specific safety data available for the combination of Tremelimumab and Olaparib. ^{1 2 3 4 5}

What makes the drug combination of Tremelimumab and Olaparib unique for treating recurrent ovarian cancer?

The combination of Tremelimumab and Olaparib is unique because it combines an immune checkpoint inhibitor (Tremelimumab) with a PARP inhibitor (Olaparib), potentially enhancing the immune system's ability to fight cancer while also targeting cancer cell DNA repair mechanisms. This dual approach may offer a novel treatment option for patients with recurrent ovarian cancer, especially those who have not responded to standard therapies. ^{2 3 6 7 8}

What data supports the effectiveness of the drug combination Tremelimumab and Olaparib for recurrent ovarian cancer?

Research shows that Olaparib, a drug used in the treatment, has shown promising results in treating ovarian cancer, especially in patients with certain genetic mutations. Additionally, studies have explored the use of Olaparib in combination with other drugs, suggesting potential benefits in treating ovarian cancer. ^{1 2 3 5 9}

Who Is on the Research Team?

Sarah F Adams

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for adults with recurrent high-grade ovarian, fallopian tube, or peritoneal cancer that's sensitive to platinum-based therapy. Participants must have a BRCA1/2 mutation and measurable disease. They should not have progressed on PARP inhibitors if used before and can't be pregnant. People with certain heart conditions, active infections, autoimmune diseases requiring recent treatment, or those on immunosuppressants are excluded.

Inclusion Criteria

My body weight is over 30 kg.

Your white blood cell count is at least 1,500 per microliter.

I have used a PARP inhibitor for my BRCA1 or BRCA2 mutation.

Exclusion Criteria

I have moderate to severe nerve pain or damage.

I have an autoimmune disease treated with medication in the last 2 years.

I do not have any serious ongoing illnesses that could affect my participation in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive olaparib with or without tremelimumab. Tremelimumab is administered every 4 weeks for 4 doses, then every 12 weeks for up to 2 years.

Up to 2 years

Regular visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs monthly for 3 months, then every 3 months for 2 years, followed by every 6 months for 3 years.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib
• Tremelimumab

Trial Overview The study is testing the effectiveness of combining Olaparib (a PARP inhibitor) with Tremelimumab (an immunotherapy drug) versus using Olaparib alone in patients whose cancer has returned. It aims to see if this combination helps the immune system better attack cancer cells and prevents them from repairing themselves.

How Is the Trial Designed?

Group I: Arm II (olaparib, tremelimumab) Experimental Treatment 4 Interventions

Patients receive olaparib as in Arm I. Patients also receive tremelimumab IV over 60 minutes on day 1. Cycles of tremelimumab repeat every 4 weeks for 4 doses and then every 12 weeks for up to 2 years total in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI as well as blood sample collection throughout the trial.

Group II: Arm I (olaparib) Active Control 4 Interventions

Patients receive olaparib PO BID in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI as well as blood sample collection throughout the trial.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Published Research Related to This Trial

A pilot study in Korea is investigating biomarker-driven targeted therapies for 68 patients with platinum-resistant recurrent ovarian cancer, focusing on HRD and PD-L1 status to tailor treatments.

Patients will receive different combinations of treatments based on their biomarker status, with the primary goal of assessing the response rate 6 months after starting treatment, highlighting a personalized approach to cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An umbrella study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer: a Korean Gynecologic Oncology Group study (KGOG 3045), AMBITION. Lee, JY., Yi, JY., Kim, HS., et al.[2020]

Olaparib (OLA) monotherapy showed a similar overall objective response rate (ORR) compared to chemotherapy (CT) in patients with relapsed ovarian cancer, with ORR of 24.3% for OLA and 28.3% for CT, indicating comparable efficacy.

In patients with platinum-resistant ovarian cancer (PROC) who had received more than four prior lines of treatment, OLA demonstrated a higher ORR of 22.9% compared to 0% for CT, suggesting that OLA may be more effective in heavily pretreated cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized CLIO/BGOG-ov10 trial of olaparib monotherapy versus physician's choice chemotherapy in relapsed ovarian cancer. Vanderstichele, A., Loverix, L., Busschaert, P., et al.[2022]

Olaparib significantly improves overall survival in patients with recurrent platinum-sensitive ovarian cancer, with a hazard ratio of 1.24 based on a meta-analysis of 7 randomized controlled trials involving 2406 patients.

However, the treatment is associated with a higher incidence of adverse events, particularly for grades 3 or higher, indicating that while olaparib is effective, it also carries a risk of significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review of Olaparib in the Treatment of Recurrent Platinum Sensitive Ovarian Cancer. Chen, Q., Li, X., Zhang, Z., 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 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]

Olaparib, approved by the FDA for patients with advanced ovarian cancer carrying BRCA mutations, showed a 34% objective response rate in a trial of 137 patients who had undergone three or more prior chemotherapy treatments, with a median response duration of 7.9 months.

Common side effects included anemia, nausea, and fatigue, with a small risk (2%) of developing myelodysplastic syndrome or acute myeloid leukemia, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with Three or More Lines of Chemotherapy. Kim, G., Ison, G., McKee, AE., 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 effective first-line maintenance treatment for adults with advanced ovarian cancer who have responded to platinum-based chemotherapy, significantly improving progression-free survival compared to placebo in phase III trials.

When combined with bevacizumab, olaparib further enhances treatment efficacy in patients with homologous recombination deficiency (HRD), but does not show benefits in HRD-negative tumors, indicating its targeted effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer. Paik, J.[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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

An umbrella study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer: a Korean Gynecologic Oncology Group study (KGOG 3045), AMBITION. [2020]

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

Randomized CLIO/BGOG-ov10 trial of olaparib monotherapy versus physician's choice chemotherapy in relapsed ovarian cancer. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Systematic Review of Olaparib in the Treatment of Recurrent Platinum Sensitive Ovarian Cancer. [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

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

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

FDA Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with Three or More Lines of Chemotherapy. [2022]

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

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

8. France pubmed.ncbi.nlm.nih.gov

Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer. [2022]

9. 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]