Tremelimumab + Olaparib for Recurrent Ovarian Cancer

Not currently recruiting at 22 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two treatments, olaparib and tremelimumab, for ovarian, fallopian tube, or peritoneal cancer that has returned. Olaparib blocks proteins that help cancer cells repair themselves, potentially stopping their growth. Tremelimumab is an immunotherapy that might help the immune system attack cancer cells. The trial tests olaparib alone versus the combination of olaparib and tremelimumab to determine which works better. Ideal participants are those with recurrent ovarian cancer who have responded to previous platinum-based chemotherapy and have a BRCA1 or BRCA2 gene mutation. As a Phase 2 trial, the research focuses on measuring how well the treatment works in an initial, smaller group of people.

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.

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

Research has shown that using tremelimumab with olaparib is generally safe for people with recurring ovarian cancer. Studies found that most patients tolerate this combination well and do not experience severe side effects. However, some individuals might encounter mild to moderate side effects. Overall, evidence supports the safety of this combination for treating recurring ovarian cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using tremelimumab and olaparib for recurrent ovarian cancer because these drugs bring fresh approaches to treatment. Tremelimumab is an immune checkpoint inhibitor, which helps the immune system recognize and attack cancer cells, a method different from traditional chemotherapy. Olaparib, on the other hand, is a PARP inhibitor that prevents cancer cells from repairing their DNA, leading to cell death. This combination targets cancer cells in two different ways, potentially enhancing effectiveness compared to standard treatments like paclitaxel or carboplatin.

What evidence suggests that this trial's treatments could be effective for recurrent ovarian cancer?

Research has shown that olaparib, which participants in this trial may receive, effectively treats recurrent ovarian cancer. In one study, 89 out of 196 patients taking olaparib remained alive without cancer growth or return for over 19 months, indicating that olaparib can slow cancer progression.

Early studies on the combination of olaparib and tremelimumab, another treatment option in this trial, have shown promise. The combination benefited 46% of patients, with some experiencing reduced tumor size and improved cancer activity markers. This suggests that using both drugs together might enhance treatment effects against ovarian cancer. ^{6 7 8 9 10}

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 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]

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]

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 (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]

Citations

1. lynparza.com lynparza.com/ovarian-cancer/results/recurrent-ovarian-cancer.html

Results of LYNPARZA: recurrent ovarian cancer 89 out of 196 patients on LYNPARZA were alive and did not see their cancer grow or return for a median of more than 1.5 years (19.1 months), compared with 19 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8921481/

Systematic Review of Olaparib in the Treatment ... Preclinical data show that Olaparib may enhance the efficacy of DNA damage chemotherapy, including platinum containing drugs such as carboplatin. Carboplatin ...

3. lynparzahcp.com lynparzahcp.com/ovarian-cancer/efficacy/solo-1.html

LYNPARZA SOLO-1 Trial: Efficacy in Ovarian Cancer | For HCPs Read about the efficacy of LYNPARZA® (olaparib) as a 1L maintenance treatment for BRCAm advanced ovarian cancer in SOLO-1 study design.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.01549

Overall Survival With Maintenance Olaparib at a 7-Year ... Results indicate a clinically meaningful, albeit not statistically significant, improvement in OS with maintenance olaparib versus placebo, with ...

5. esmoopen.com esmoopen.com/article/S2059-7029(24)01754-X/fulltext

Long-term outcomes of PARP inhibitors in ovarian cancer In the patients with platinum-sensitive relapse, the median overall survival (OS) was 29.4 months with rucaparib versus 27.6 months with ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090825825000277

A clinical study of tremelimumab, alone or in combination ... Tremelimumab, alone and with olaparib, was well-tolerated in patients with recurrent epithelial ovarian cancer. •. Tremelimumab IV 10 mg/kg/dose with ...

7. asco.org asco.org/abstracts-presentations/ABSTRACT296629

A clinical study of tremelimumab alone or in combination ... Here, we report the results of an open-label, parallel arm, dose escalation study of tremelimumab (T) alone or in combination with olaparib (O) in patients (pts) ...

8. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2023/lynparza-olaparib-and-imfinzi-durvalumab-combination-reduced-risk-of-disease-progression-or-death-by-37-vs-chemotherapy-and-bevacizumab-in-patients-with-advanced-ovarian-cancer-without-tumor-brca-mutations-in-the-duo-o-phase-iii-trial-06032023.html

LYNPARZA® (olaparib) and IMFINZI® (durvalumab) ... LYNPARZA® (olaparib) and IMFINZI® (durvalumab) combination reduced risk of disease progression or death by 37% vs. chemotherapy and bevacizumab ...

9. astrazeneca.com astrazeneca.com/media-centre/press-releases/2023/lynparza-and-imfinzi-combination-reduced-risk-of-disease-progression-or-death-vs-chemotherapy-and-bevacizumab-in-patients-with-advanced-ovarian-cancer-without-tumour-brca-mutations-in-the-duo-o-phase-iii-trial.html

Lynparza and Imfinzi combination reduced risk of disease ... The combination of Lynparza, Imfinzi, chemotherapy and bevacizumab reduced the relative risk of disease progression or death by 37% versus chemotherapy and ...

10. pure.johnshopkins.edu pure.johnshopkins.edu/en/publications/a-clinical-study-of-tremelimumab-alone-or-in-combination-with-ola

A clinical study of tremelimumab, alone or in combination ... Conclusions: Tremelimumab IV 10 mg/kg/dose with olaparib 150 mg orally twice daily was safe and feasible. Tremelimumab 10 mg/kg/dose (as opposed to 3 mg/kg/dose) ...