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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a combination of three treatments for individuals with recurrent ovarian cancer sensitive to platinum-based therapies. The treatments under investigation are cisplatin (a common cancer drug), rintatolimod (an immune system booster), and pembrolizumab (a type of immunotherapy). Suitable candidates for this trial have ovarian cancer that initially responded to platinum treatments and has recurred in the abdominal area. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing participants an opportunity to contribute to groundbreaking research.

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.

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

Research shows that the combination of cisplatin, rintatolimod, and pembrolizumab is being tested for safety in treating recurring ovarian cancer. Previous studies have found that using rintatolimod and pembrolizumab together may be more effective than using pembrolizumab alone. While these studies mainly focus on the treatment's effectiveness, they report no major safety issues specifically related to the combination.

Cisplatin and pembrolizumab are already used for other conditions, so their safety is well understood. Rintatolimod is newer but has shown promise when combined with other treatments. This trial is in an early stage, and researchers are still collecting detailed safety information. However, current evidence does not suggest any unusual safety risks, which is encouraging for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this chemo-immunotherapy combination for recurrent ovarian cancer because it integrates unique mechanisms that are not typical in standard treatments. While traditional therapies often rely on chemotherapy alone, this approach combines cisplatin with pembrolizumab, an immune checkpoint inhibitor, and rintatolimod, an immune system activator. This combo aims to enhance the body's immune response against cancer cells, potentially improving effectiveness beyond what chemotherapy alone can achieve. Additionally, the delivery method of intraperitoneal cisplatin allows for direct targeting of cancer cells in the abdominal cavity, which could enhance drug concentration at the tumor site and reduce systemic side effects.

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

Research has shown that combining rintatolimod and pembrolizumab with cisplatin might improve treatment for recurring ovarian cancer. In this trial, participants will receive this combination treatment. Studies have found that this combination can help the immune system fight cancer cells more effectively. Rintatolimod and pembrolizumab together have proven more effective than pembrolizumab alone. Early evidence suggests that these drugs work better together than separately. Overall, this combination of treatments shows promise in effectively addressing recurrent ovarian cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Robert Edwards, MD

Principal Investigator

UPMC Hillman Cancer Center

Are You a Good Fit for This Trial?

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.

Patients of childbearing potential must have a negative pregnancy test, discontinue breastfeeding if applicable, and agree to follow contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

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]

Citations

1. aimimmuno.com aimimmuno.com/aim-immunotech-announces-positive-top-line-protocol-planned-interim-report-data-from-the-study-of-ampligen-combined-with-pembrolizumab-for-the-treatment-of-recurrent-ovarian-cancer/

AIM ImmunoTech Announces Positive Top-Line, Protocol ... Combining Ampligen (rintatolimod) with Keytruda (pembrolizumab) in the treatment of recurrent ovarian cancer may have a powerful synergistic effect.

2. cancernetwork.com cancernetwork.com/view/rintatolimod-combo-yields-clinical-benefit-in-recurrent-ovarian-cancer

Rintatolimod Combo Yields Clinical Benefit in Recurrent ... Treatment with rintatolimod (Ampligen) plus pembrolizumab (Keytruda) demonstrated a potential improvement in efficacy compared with pembrolizumab monotherapy.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03734692

Study Details | NCT03734692 | Systemic Immune ... The study will use an IP neoadjuvant approach (IP chemoimmunotherapy of cisplatin with IP rintatolimod and IV infusion of pembrolizumab), followed by interval ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9106847/

Phase I trial combining chemokine-targeting with loco ... Our preclinical data further show that rintatolimod/IFNα-activated ovarian cancer tumors show strongly enhanced chemotactic activity for ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT03734692

NCT03734692 ... Ampligen, pembrolizumab and cisplatin in platinum-sensitive subjects with recurrent ovarian cancer. ... Data from Phase 2 Study Evaluating Ampligen for the ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11762523/

Immunotherapy in Recurrent Ovarian Cancer - PMC Conclusions: Immunotherapy significantly advances recurrent ovarian cancer treatment, with various combinations potentially improving outcomes.