Chemo-Immunotherapy for Recurrent Ovarian Cancer

Overseen By Robert Edwards, MD

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Robert Edwards

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Pregnancy, Active infection, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 10

Duration: 18 weeks

45 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase II single arm efficacy/safety trial that will evaluate the effectiveness of combining intensive locoregional intraperitoneal (IP) chemoimmunotherapy of cisplatin with IP rintatolimod (TLR-3 agonist) and IV infusion of the checkpoint inhibitor pembrolizumab (IVP) for patients with recurrent platinum-sensitive ovarian cancer (OC).

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain treatments like systemic anti-cancer therapy or immunosuppressive therapy close to the trial start. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination of Cisplatin, Pembrolizumab, and Rintatolimod for recurrent ovarian cancer?

Research shows that combining pembrolizumab with platinum-based drugs like cisplatin can enhance the immune system's ability to recognize and attack ovarian cancer cells, although the response rate to pembrolizumab alone is low. Adding chemotherapy to immunotherapy may improve outcomes in platinum-resistant ovarian cancer. ^{1 2 3 4 5}

Is the chemo-immunotherapy treatment for recurrent ovarian cancer safe?

The combination of pembrolizumab and cisplatin has been studied for safety in recurrent ovarian cancer, showing that while it can cause side effects like fatigue, nausea, and rash, these are generally manageable. Pembrolizumab has also been approved for other cancers, with common side effects including fatigue and nausea, and some immune-related reactions like inflammation of the lungs or liver. ^{1 2 6 7 8}

How is the chemo-immunotherapy treatment for recurrent ovarian cancer different from other treatments?

This treatment combines cisplatin, pembrolizumab, and rintatolimod, which is unique because it pairs a platinum-based chemotherapy with an immune checkpoint inhibitor and an immune modulator, aiming to enhance the immune system's ability to recognize and attack cancer cells, especially in cases where the cancer is resistant to standard platinum therapies. ^{1 2 3 9 10}

Research Team

Robert Edwards, MD

Principal Investigator

UPMC Hillman Cancer Center

Eligibility Criteria

This trial is for adults over 18 with recurrent platinum-sensitive ovarian cancer, who can undergo laparoscopy and have no major abdominal issues or severe allergies to the drugs used. They must not be pregnant, breastfeeding, or planning pregnancy soon. Participants should be in good physical condition (ECOG 0-1) and agree to follow-up monitoring.

Inclusion Criteria

Patients must agree to the protocol designated clinical monitoring to receive the study regimens.

The participant provides written informed consent for the trial.

I am 18 years old or older.

Exclusion Criteria

A WOCBP who has a positive urine pregnancy test within 72 hours prior to infusion of treatment regimen.

I am not allergic to pembrolizumab or cisplatin.

Patients with known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive six cycles of intraperitoneal chemoimmunotherapy with cisplatin, rintatolimod, and pembrolizumab at 3-week intervals

18 weeks

6 visits (in-person)

Surgery

Interval cytoreduction surgery to remove residual tumor, followed by two additional courses of chemoimmunotherapy

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including catheter removal and biopsies

12 weeks

3 visits (in-person)

Long-term Follow-up

Participants are monitored for progression-free survival

up to 4 years

Treatment Details

Interventions

• Cisplatin
• Pembrolizumab
• Rintatolimod

Trial Overview The study tests a combination of intraperitoneal cisplatin and rintatolimod with IV pembrolizumab on patients with first or second recurrence of ovarian cancer. It aims to assess safety and effectiveness in those who responded well previously to platinum-based therapy.

Participant Groups

Group I: cisplatin + rintatolimod + pembrolizumab Experimental Treatment 3 Interventions

Intraperitoneal (IP) cisplatin 50mg/m\^2 solution with IP rintatolimod 200 mg solution and IV pembrolizumab 200 mg solution.

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Robert Edwards

Lead Sponsor

Trials

1

Recruited

50+

AIM ImmunoTech Inc.

Industry Sponsor

Trials

15

Recruited

710+

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 study involving patients with recurrent platinum-resistant ovarian cancer, the combination of pembrolizumab, cisplatin, and gemcitabine resulted in an overall response rate of 60%, but the duration of response was relatively short at 4.9 months.

The addition of pembrolizumab did not show a significant benefit over chemotherapy alone, leading to the decision to close the trial for further accrual after an interim analysis indicated modest outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. Walsh, CS., Kamrava, M., Rogatko, A., et al.[2022]

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]

Platinum-resistant ovarian cancer is a challenging disease with a poor prognosis, often characterized by low immune cell infiltration, leading to low response rates (less than 8%) to anti-PD1/PD-L1 therapies.

Emerging strategies to enhance treatment efficacy include combining immune checkpoint inhibitors with chemotherapy, anti-angiogenic agents, and other immunotherapies, with ongoing studies aiming to identify optimal combinations and predictive biomarkers for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges for immunotherapy for the treatment of platinum resistant ovarian cancer. Le Saux, O., Ray-Coquard, I., Labidi-Galy, SI.[2022]

In a phase II study involving 59 women with recurrent, platinum-sensitive ovarian cancer, the combination of carboplatin, GM-CSF, and rIFN-gamma1b resulted in a 56% overall response rate, with 17% achieving complete response and 39% partial response.

The treatment was associated with common side effects such as bone marrow suppression and fatigue, but responders reported improved quality of life, suggesting that this regimen may be a promising option for further investigation in ovarian cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of GM-CSF and rIFN-gamma1b plus carboplatin for the treatment of recurrent, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer. Schmeler, KM., Vadhan-Raj, S., Ramirez, PT., et al.[2021]

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]

In a study of 94 patients with relapsed platinum-resistant ovarian cancer, dose-dense cisplatin combined with gemcitabine resulted in a median progression-free survival of 4.4 months and an overall survival of 7.6 months, indicating modest efficacy for this treatment regimen.

The treatment was associated with manageable side effects, with the most common severe adverse events being thrombocytopenia (20%), anemia (18%), and neutropenia (14%), suggesting that while the therapy has risks, it can be tolerated with appropriate supportive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-dense cisplatin with gemcitabine for relapsed platinum-resistant ovarian cancer. Morgan, RD., Clamp, AR., Zhou, C., et al.[2021]

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]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Cytoreductive surgery followed by platinum-based chemotherapy, particularly with carboplatin, remains the standard treatment for advanced epithelial ovarian cancer, but most patients are not cured, highlighting the need for improved therapies.

Paclitaxel, a novel agent effective in platinum-resistant ovarian cancer, is being tested in combination with platinum compounds in clinical trials for previously untreated patients, aiming to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. Ozols, RF.[2015]

Patients with recurrent ovarian cancer are categorized as either platinum-sensitive or platinum-resistant, which influences treatment options; platinum-sensitive patients often benefit from re-treatment with paclitaxel/platinum combinations, while platinum-resistant patients may receive single-agent therapies like altretamine or topotecan.

For platinum-sensitive patients with minimal residual disease, intensive intraperitoneal therapy with cisplatin and paclitaxel shows the most promise for long-term disease-free survival, highlighting the importance of tailored treatment strategies based on disease characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of refractory and recurrent ovarian cancer. Alberts, DS.[2005]

References

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

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. [2022]

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. England pubmed.ncbi.nlm.nih.gov

Challenges for immunotherapy for the treatment of platinum resistant ovarian cancer. [2022]

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

A phase II study of GM-CSF and rIFN-gamma1b plus carboplatin for the treatment of recurrent, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer. [2021]

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

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

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

Dose-dense cisplatin with gemcitabine for relapsed platinum-resistant ovarian cancer. [2021]

7. 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]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

Treatment of ovarian cancer: current status. [2015]

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

Treatment of refractory and recurrent ovarian cancer. [2005]