Chemo + Immunotherapy for Advanced Ovarian Cancer

Overseen By Rebecca Arend, MD, MSPH

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Alabama at Birmingham

Must be taking: Carboplatin, Paclitaxel

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Mucinous tumors, Pneumonitis, MDS/AML, 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: 1

20 Participants Needed

Trial Summary

What is the purpose of this trial?

this is a trial evaluating three chemotherapy agents in patients with newly diagnosed ovarian cancer patients that are Stage III or Stage IV prior to surgery to remove the tumor. After surgery there will be additional chemotherapy given.

Do I need to stop my current medications to join the trial?

The trial requires a washout period (time without taking certain medications) for specific drugs that affect liver enzymes, such as certain antibiotics and antifungals, before starting olaparib. If you are taking these medications, you may need to stop them for 2 to 5 weeks before joining the trial. For other medications, the protocol does not specify, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug combination of Carboplatin, Olaparib, and Pembrolizumab for advanced ovarian cancer?

Research shows that combining pembrolizumab with carboplatin has shown activity in recurrent ovarian cancer, and the combination of olaparib and carboplatin has been found to be tolerable and beneficial in heavily pretreated ovarian cancer patients, suggesting potential effectiveness of this drug combination. ^{1 2 3 4 5}

Is the combination of chemo and immunotherapy safe for treating advanced ovarian cancer?

The combination of olaparib and carboplatin has been found to be generally tolerable, though it can cause side effects like low blood cell counts (neutropenia and thrombocytopenia) and anemia. Pembrolizumab, an immune therapy, can cause serious lung inflammation (pneumonitis) in a small percentage of patients. Overall, these treatments have shown to be safe for many patients, but they do have potential risks. ^{2 3 4 6 7}

How does the chemo and immunotherapy treatment for advanced ovarian cancer differ from other treatments?

This treatment combines chemotherapy with immunotherapy, which is unique because chemotherapy can enhance the immune system's ability to recognize and attack cancer cells, potentially improving the effectiveness of immunotherapy. This approach is different from traditional treatments that typically use chemotherapy or immunotherapy alone. ^{2 3 8 9 10}

Research Team

Rebecca C. Arend

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

This trial is for women over 18 with advanced (Stage III/IV) ovarian cancer, who haven't had treatment yet. They should be in good health otherwise, not pregnant or breastfeeding, and willing to use contraception. Women must have a certain level of organ function and a specific tumor type to join.

Inclusion Criteria

I am a woman aged 18 or older.

I am eligible for carboplatin and paclitaxel chemotherapy before surgery to reduce my tumor size.

My blood counts and organ functions are within the required ranges for the study.

Exclusion Criteria

I am taking strong or moderate drugs that affect liver enzymes and can't stop them for the study.

I have not had a whole blood transfusion in the last 4 months but may have had other blood component transfusions over a month ago.

I have a serious health condition that is not under control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive a one-cycle lead-in of carboplatin (with or without) paclitaxel followed by three cycles of carboplatin, paclitaxel, and pembrolizumab prior to interval debulking surgery

12-20 weeks

Multiple visits for chemotherapy administration

Interval Debulking Surgery

Participants undergo interval debulking surgery after neoadjuvant chemotherapy

1 week

1 surgical visit

Post-Surgery Chemotherapy

Participants receive three cycles of carboplatin, paclitaxel, and pembrolizumab after interval debulking surgery

9-12 weeks

Multiple visits for chemotherapy administration

Maintenance Therapy

Participants receive maintenance therapy with olaparib and pembrolizumab, with optional bevacizumab if no complete response is achieved

24-36 months

Regular visits for maintenance therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Regular follow-up visits

Treatment Details

Interventions

• Carboplatin
• Olaparib
• Pembrolizumab

Trial Overview The study tests three chemotherapy drugs—Carboplatin, Paclitaxel (Taxol), and Pembrolizumab—before surgery to remove the tumor. After surgery, Olaparib combined with Pembrolizumab is given as maintenance therapy to prevent cancer from coming back.

Participant Groups

Group I: Carbo/taxol/pembro followed by maintenance of olaparib/pembro post-surgery Experimental Treatment 2 Interventions

neoadjuvant carbo/taxol/pembro followed by maintenance olaparib/pembro post- surgery

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Merck Sharp & Dohme LLC

Industry 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

Findings from Research

In a phase Ib trial involving 26 patients with advanced PD-L1-positive ovarian cancer, pembrolizumab demonstrated a confirmed objective response rate of 11.5%, indicating some level of antitumor activity, with 1 complete response and 2 partial responses observed.

The treatment was generally well-tolerated, with 73.1% of patients experiencing treatment-related adverse events, but no deaths or treatment discontinuations due to these events, suggesting that pembrolizumab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Varga, A., Piha-Paul, S., Ott, PA., et al.[2019]

The combination of pembrolizumab and carboplatin was found to be well-tolerated and showed activity in patients with recurrent platinum-resistant ovarian cancer, with a median overall survival of 11.3 months.

Patients with a higher ratio of peripheral CD8+PD1+Ki67+ T cells to tumor burden had significantly longer overall survival, suggesting this ratio could help identify those who may benefit more from this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with low-dose carboplatin for recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer: survival and immune correlates. Liao, JB., Gwin, WR., Urban, RR., et al.[2022]

The combination of olaparib and carboplatin is tolerable and shows clinical benefit in patients with BRCA wild-type high-grade serous ovarian carcinoma, with a clinical benefit rate of 64% in heavily pretreated patients.

The maximum tolerated dose was established at olaparib 400 mg twice daily with carboplatin AUC4, although significant side effects like neutropenia and thrombocytopenia were observed, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/Ib study of olaparib and carboplatin in heavily pretreated recurrent high-grade serous ovarian cancer at low genetic risk. Lampert, EJ., Hays, JL., Kohn, EC., et al.[2023]

In a study of 120 ovarian cancer patients, the combination of olaparib with paclitaxel and carboplatin significantly improved the objective remission rate and disease control rate compared to the standard treatment with paclitaxel and carboplatin alone.

The addition of olaparib also resulted in lower levels of tumor markers and a reduced rate of tumor metastasis after one year, all without increasing the incidence of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib and paclitaxel in combination with carboplatin in treatment of ovarian cancer: influence on disease control. Zhang, H., Zhang, Y.[2022]

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]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

The combination of olaparib and carboplatin was found to be safe and effective in treating breast and ovarian cancer in patients with germline BRCA1 or BRCA2 mutations, with 50% of patients showing a partial response and one patient achieving a complete response.

Proteomic analysis indicated that high levels of FOXO3a expression before treatment may predict a better response to the therapy, suggesting a potential biomarker for future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses. Lee, JM., Hays, JL., Annunziata, CM., et al.[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]

The GEICO1601-ROLANDO trial is a Phase II study investigating the combination of olaparib (a PARP inhibitor) and pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer, regardless of BRCA mutation status.

The primary goal of the trial is to assess progression-free survival at 6 months, with additional measures including response rate, disease control rate, quality of life, and overall survival, aiming to improve treatment outcomes in a population with historically low response to PARP inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GEICO1601-ROLANDO: a multicentric single arm Phase II clinical trial to evaluate the combination of olaparib and pegylated liposomal doxorubicin for platinum-resistant ovarian cancer. Perez-Fidalgo, JA., Iglesias, M., Bohn, U., et al.[2020]

In a phase III trial involving 266 patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer, olaparib showed a significantly higher objective response rate (ORR) of 72.2% compared to 51.4% for nonplatinum chemotherapy, indicating its efficacy as a treatment option.

Olaparib also demonstrated a longer progression-free survival (PFS) of 13.4 months versus 9.2 months for chemotherapy, suggesting it not only works better but also helps patients live longer without disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial. Penson, RT., Valencia, RV., Cibula, D., et al.[2021]

References

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

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab with low-dose carboplatin for recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer: survival and immune correlates. [2022]

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

Phase I/Ib study of olaparib and carboplatin in heavily pretreated recurrent high-grade serous ovarian cancer at low genetic risk. [2023]

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

Olaparib and paclitaxel in combination with carboplatin in treatment of ovarian cancer: influence on disease control. [2022]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses. [2022]

8. 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]

9. England pubmed.ncbi.nlm.nih.gov

GEICO1601-ROLANDO: a multicentric single arm Phase II clinical trial to evaluate the combination of olaparib and pegylated liposomal doxorubicin for platinum-resistant ovarian cancer. [2020]

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

Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial. [2021]