Rucaparib + Nivolumab for Ovarian Cancer

(ATHENA Trial)

Recruiting at 248 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

1097 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 3, randomized, multinational, double-blind, dual placebo-controlled, 4-arm study evaluating rucaparib and nivolumab as maintenance treatment following response to front-line treatment in newly diagnosed ovarian cancer patients. Response to treatment will be analyzed based on homologous recombination (HR) status of tumor samples.

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.

What data supports the effectiveness of the drug combination Rucaparib and Nivolumab for ovarian cancer?

Rucaparib has shown potential as a maintenance treatment for ovarian cancer, while Nivolumab, when used alone, has limited effectiveness. However, combining Nivolumab with other treatments, like Rucaparib, might enhance its benefits, as suggested by strategies to improve outcomes in ovarian cancer. ^{1 2 3 4 5}

Is the combination of Rucaparib and Nivolumab safe for treating ovarian cancer?

Rucaparib has been studied for ovarian cancer and is generally safe, but it can cause side effects like nausea, fatigue, and anemia. Most side effects are mild and manageable with treatment adjustments. There is no specific safety data available for the combination of Rucaparib and Nivolumab. ^{6 7 8 9 10}

How is the drug Rucaparib + Nivolumab unique for treating ovarian cancer?

Rucaparib is a unique drug for ovarian cancer because it is a PARP inhibitor, which means it blocks proteins that help repair DNA damage in cancer cells, making it particularly effective in cancers with BRCA mutations. When combined with Nivolumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, this combination offers a novel approach by targeting both DNA repair and immune evasion mechanisms in ovarian cancer. ^{2 9 11 12 13}

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. United States 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). [2023]

2. India pubmed.ncbi.nlm.nih.gov

Rucabarib: A new lease of life for ovarian cancer patients. [2022]

3. United States 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. [2021]

4. United States 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. [2021]

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

Immune checkpoint inhibitors in ovarian cancer: where do we stand? [2021]

6. France pubmed.ncbi.nlm.nih.gov

Management of Adverse Events During Rucaparib Treatment for Relapsed Ovarian Cancer: A Review of Published Studies and Practical Guidance. [2023]

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

Rucaparib: A Poly(ADP-Ribose) Polymerase Inhibitor for BRCA-Mutated Relapsed Ovarian Cancer. [2022]

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

Efficacy and safety of rucaparib treatment in patients with BRCA-mutated, relapsed ovarian cancer: final results from Study 10. [2023]

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

Rucaparib: a novel PARP inhibitor for BRCA advanced ovarian cancer. [2019]

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

FDA Approval Summary: Rucaparib for the Treatment of Patients with Deleterious BRCA Mutation-Associated Advanced Ovarian Cancer. [2022]

11. France pubmed.ncbi.nlm.nih.gov

Rucaparib: A Review in Ovarian Cancer. [2021]

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

Characterization of patients with long-term responses to rucaparib treatment in recurrent ovarian cancer. [2022]

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

Emerging treatment options for ovarian cancer: focus on rucaparib. [2022]