Rucaparib + Nivolumab for Ovarian Cancer

(ATHENA Trial)

Not currently recruiting at 296 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: ppharmaand GmbH

Must be taking: Platinum-based chemotherapy

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Active malignancy, Brain metastases, Autoimmune, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining rucaparib and nivolumab (also known as Opdivo, an immunotherapy drug) can prevent ovarian cancer from returning after initial treatment. It targets patients recently diagnosed with advanced ovarian cancer who responded well to their first chemotherapy and surgery. Participants must have completed specific surgeries and chemotherapy and provide enough tumor tissue for analysis. The trial includes four groups to compare the effects of the treatments and placebos (inactive substances). This research aims to find better ways to maintain remission in ovarian cancer patients. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on certain treatments like corticosteroids or other immunosuppressive medications.

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

Research shows that both rucaparib and nivolumab have been studied separately and together for treating ovarian cancer. Rucaparib alone has helped some patients live longer without their cancer worsening. However, adding nivolumab to rucaparib did not always improve outcomes.

Both drugs have undergone safety testing. Rucaparib and nivolumab are usually well-tolerated, but they can cause side effects. Common side effects of rucaparib include nausea, tiredness, and changes in blood cell counts. Nivolumab, an immunotherapy, may cause tiredness, skin rash, and inflammation in different body parts. The severity of these side effects can vary among patients.

This trial is in a later stage, indicating existing knowledge about the safety of these drugs. Both drugs are also approved for other conditions, indicating a known safety profile. However, individual reactions can differ, so discussing potential risks and benefits with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of rucaparib and nivolumab for ovarian cancer because it offers a novel approach by combining a PARP inhibitor with an immune checkpoint inhibitor. Rucaparib specifically targets and inhibits the PARP enzyme, which is crucial for repairing DNA damage in cancer cells, potentially leading to their death. Nivolumab, on the other hand, helps the immune system recognize and attack cancer cells by blocking the PD-1 pathway. Unlike traditional chemotherapy, which targets rapidly dividing cells indiscriminately, this combination aims to enhance the precision of attack on cancer cells while harnessing the body's immune response, potentially reducing side effects and improving outcomes.

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

Research shows that rucaparib alone holds promise for treating ovarian cancer. Patients taking rucaparib experienced a median progression-free survival (PFS) of 20.2 months, meaning the cancer did not worsen, compared to 9.2 months for those on a placebo. In this trial, participants in Arm A will receive a combination of rucaparib and nivolumab, while Arm B will receive rucaparib with an IV placebo. Arm C will receive a placebo with nivolumab, and Arm D will receive both oral and IV placebos. Previous studies suggest that adding nivolumab to rucaparib did not improve results and actually led to a shorter PFS. Overall, rucaparib appears effective on its own, but combining it with nivolumab might not provide additional benefits. ^{2 3 4 6 7}

Who Is on the Research Team?

Keiichi Fujiwara, MD, PhD

Principal Investigator

Lead Investigator for Asia

Bradley Monk, MD, FACS, FACOG

Principal Investigator

Lead Investigator and Coordinating Investigator for North America

Rebecca Kristeleit, Bsc MBChB FRCP PhD

Principal Investigator

Coordinating Investigator for Europe and the Middle East

Are You a Good Fit for This Trial?

This trial is for adults with advanced ovarian, fallopian tube, or primary peritoneal cancer who've had surgery and responded to first-line platinum-based chemotherapy. It's not for those with autoimmune diseases, other active cancers, brain metastases, prior treatments besides platinum chemo, lung conditions or on high-dose steroids/immunosuppressants.

Inclusion Criteria

My tumor can be tested with enough tissue.

I have been newly diagnosed with advanced ovarian, fallopian tube, or peritoneal cancer.

I've had surgery to remove my ovaries and part of the lining of my abdomen.

Exclusion Criteria

My cancer is a type of sarcoma, borderline tumor, or mucinous tumor.

I have another type of cancer that is currently active.

I am currently taking more than 10 mg of prednisone daily or other immunosuppressive drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive maintenance treatment with rucaparib and/or nivolumab following response to front-line platinum-based chemotherapy

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Rucaparib

Trial Overview The study tests Rucaparib and Nivolumab as maintenance treatments after initial success with chemotherapy in ovarian cancer patients. It's a Phase 3 trial where participants are randomly assigned to receive either the drugs or placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: Japanese Open-label Safety Cohort Experimental Treatment 2 Interventions

Oral rucaparib + IV nivolumab

Group II: Arm C Experimental Treatment 2 Interventions

Oral placebo + IV nivolumab

Group III: Arm B Experimental Treatment 2 Interventions

Oral rucaparib + IV placebo

Group IV: Arm A Experimental Treatment 2 Interventions

Oral rucaparib + intravenous (IV) nivolumab

Group V: Arm D Placebo Group 2 Interventions

Oral placebo + IV placebo

Who Is Running the Clinical Trial?

ppharmaand GmbH

Lead Sponsor

Trials

12

Recruited

1,900+

pharmaand GmbH

Lead Sponsor

Trials

22

Recruited

4,300+

Clovis Oncology, Inc.

Lead Sponsor

Trials

65

Recruited

11,100+

Patrick J. Mahaffy

Clovis Oncology, Inc.

Chief Executive Officer since 2009

BA from Haverford College, MBA from Columbia University

Lindsey Rolfe

Clovis Oncology, Inc.

Chief Medical Officer since 2015

Specialist accreditation in pharmaceutical medicine

zr Pharma & GmbH

Lead Sponsor

Trials

21

Recruited

4,200+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Gynecologic Oncology Group

Collaborator

Trials

251

Recruited

65,400+

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Collaborator

Trials

41

Recruited

19,200+

Foundation Medicine

Industry Sponsor

Trials

37

Recruited

17,600+

Published Research Related to This Trial

In a phase III study involving 316 patients with platinum-resistant ovarian cancer, nivolumab did not improve overall survival compared to chemotherapy (gemcitabine or pegylated liposomal doxorubicin), with median overall survival of 10.1 months for nivolumab versus 12.1 months for chemotherapy.

Nivolumab was associated with fewer treatment-related adverse events (61.5% vs. 98.1% for chemotherapy), indicating it may be better tolerated, but it also showed worse progression-free survival (2.0 months vs. 3.8 months for chemotherapy).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA). Hamanishi, J., Takeshima, N., Katsumata, N., et al.[2023]

Rucaparib (RUBRACA) received accelerated FDA approval for treating advanced ovarian cancer in patients with BRCA mutations, showing a 54% objective response rate in a study of 106 patients who had undergone two or more prior chemotherapies.

The FoundationFocus CDx BRCA test was approved as a companion diagnostic to identify eligible patients, successfully verifying BRCA mutation status in 96% of tested cases, ensuring targeted treatment for those most likely to benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Rucaparib for the Treatment of Patients with Deleterious BRCA Mutation-Associated Advanced Ovarian Cancer. Balasubramaniam, S., Beaver, JA., Horton, S., et al.[2022]

Intra-tumoral immune cell density is a significant prognostic factor in epithelial ovarian cancer, suggesting that the immune environment plays a crucial role in disease outcomes.

Despite the rationale for using PD1/PD-L1 inhibitors in treating relapsed ovarian cancer, clinical trials have not shown promising results, leading to the exploration of combination therapies and earlier intervention strategies to improve efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors in ovarian cancer: where do we stand? Leary, A., Tan, D., Ledermann, J.[2021]

In a phase III study involving 888 patients with ovarian cancer in first clinical remission, abagovomab maintenance therapy was found to be safe and induced a measurable immune response, with common side effects including injection site reactions and fatigue.

However, the study concluded that abagovomab did not significantly prolong recurrence-free survival (RFS) or overall survival (OS) compared to placebo, indicating that it may not be an effective maintenance therapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abagovomab as maintenance therapy in patients with epithelial ovarian cancer: a phase III trial of the AGO OVAR, COGI, GINECO, and GEICO--the MIMOSA study. Sabbatini, P., Harter, P., Scambia, G., et al.[2021]

Rucaparib, a poly(ADP-ribose) polymerase inhibitor, is effective as a treatment for relapsed ovarian cancer, but 61.8% of patients experience serious adverse events (AEs), highlighting the need for careful monitoring.

Common AEs include gastrointestinal issues, fatigue, and anemia, with 16.2% of patients discontinuing treatment due to these side effects; therefore, managing these AEs is essential for maintaining treatment adherence and improving patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Adverse Events During Rucaparib Treatment for Relapsed Ovarian Cancer: A Review of Published Studies and Practical Guidance. Lorusso, D., García-Donas, J., Sehouli, J., et al.[2023]

In a study of 100 women with recurrent epithelial ovarian cancer, the combination of ipilimumab and nivolumab resulted in a significantly higher response rate (31.4%) compared to nivolumab alone (12.2%), indicating improved efficacy of the combination therapy.

The median progression-free survival was also longer for the combination group (3.9 months) compared to nivolumab alone (2 months), although both treatments had similar rates of severe adverse events, suggesting that the combination therapy is relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase II Trial of Nivolumab Versus Nivolumab and Ipilimumab for Recurrent or Persistent Ovarian Cancer: An NRG Oncology Study. Zamarin, D., Burger, RA., Sill, MW., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03522246

NCT03522246 | A Study in Ovarian Cancer Patients ... This is a Phase 3, randomized, multinational, double-blind, dual placebo-controlled, 4-arm study evaluating rucaparib and nivolumab as maintenance treatment

2. touchoncology.com touchoncology.com/gynaecological-cancers/conference-hub/addition-of-nivolumab-to-rucaparib-did-not-improve-clinical-outcomes-in-newly-diagnosed-advanced-high-grade-ovarian-cancer/

Addition of nivolumab to rucaparib did not improve clinical ... In the MONO arm, rucaparib showed sustained progression-free survival (PFS) of 20.2 months after first-line treatment. However, the COMBO arm ...

3. medscape.com medscape.com/viewarticle/nivolumab-rucaparib-not-superior-rucaparib-maintenance-tx-2024a1000gq5

Worse PFS Seen with Nivolumab-Rucaparib in Ovarian ... The study showed the combination therapy was associated with numerically shorter median PFS compared with rucaparib monotherapy in the intent-to ...

4. clin.larvol.com clin.larvol.com/trial-detail/NCT03522246

A Study in Ovarian Cancer Patients Evaluating Rucaparib ... In the intention-to-treat (ITT) population, treatment with rucaparib elicited a median PFS of 20.2 months (95% CI, 15.6-24.7) vs 9.2 months (95% CI, 8.5-12.2) ...

5. oncnursingnews.com oncnursingnews.com/view/rucaparib-maintenance-extends-progression-free-survival-in-advanced-ovarian-cancer

Rucaparib Maintenance Extends Progression-Free ... Maintenance therapy with rucaparib monotherapy improved progression-free survival compared with placebo. However, the treatment also ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03522246

NCT03522246 | A Study in Ovarian Cancer Patients ... This is a Phase 3, randomized, multinational, double-blind, dual placebo-controlled, 4-arm study evaluating rucaparib and nivolumab as maintenance treatment

7. onclive.com onclive.com/view/athena-trial-of-maintenance-rucaparib-nivolumab-in-ovarian-cancer-completes-target-enrollment

ATHENA Trial of Maintenance Rucaparib/Nivolumab in ... The pivotal phase 3 ATHENA trial, which will examine the safety and efficacy of rucaparib in combination with nivolumab as maintenance treatment.