GEN-1 + Chemo + Bevacizumab for Ovarian Cancer

(MRD Trial)

Recruiting at 3 trial locations

Overseen By Douglas Faller, MD

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Imunon

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Autoimmune disease, HIV, Hepatitis, others

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

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

Compensation: Varies

Number of Visits: Unknown

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for advanced ovarian cancer by combining the drug GEN-1 (also known as IMNN-001) with standard chemotherapy and Bevacizumab, which slows the growth of blood vessels in tumors. Researchers aim to determine if adding GEN-1 can improve treatment outcomes compared to using only chemotherapy and Bevacizumab. The trial is open to individuals diagnosed with advanced high-grade serous ovarian, fallopian tube, or primary peritoneal cancer that requires chemotherapy. Participants should not have received similar treatments before and must be free of serious infections or other significant health issues. As a Phase 1, Phase 2 trial, this study focuses on understanding how GEN-1 works in people and measuring its effectiveness in improving treatment outcomes.

Will I have to stop taking my current medications?

The trial requires that any hormonal therapy directed at the malignant tumor be stopped at least one week before the first treatment. However, hormone replacement therapy can continue. The protocol does not specify other medication restrictions, but you should discuss your current medications with the trial team.

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

Research shows that IMNN-001, when combined with chemotherapy, has promising safety results. In earlier studies, patients generally tolerated IMNN-001 well, with some even experiencing longer survival, particularly in certain groups. These studies also suggest that side effects were usually manageable.

The other treatments in this trial—Bevacizumab, Carboplatin, and Paclitaxel—have FDA approval for specific uses and are generally well-tolerated by many patients. Common side effects include nausea and tiredness, typical for many cancer treatments. Overall, strong safety data supports the use of these treatments in people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatment for ovarian cancer, which typically involves chemotherapy alone, the GEN-1 treatment in this trial adds a novel component to the mix. GEN-1 is an innovative therapy that uses a gene-mediated approach to stimulate the immune system, potentially enhancing the effectiveness of traditional chemotherapy drugs like carboplatin and paclitaxel. Researchers are particularly excited because GEN-1 is administered intraperitoneally, directly targeting the cancer cells in the abdominal cavity, which could lead to improved outcomes. Additionally, by combining GEN-1 with bevacizumab, a drug that inhibits blood vessel growth in tumors, this approach aims to deliver a powerful one-two punch against ovarian cancer.

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

This trial will compare the effects of adding IMNN-001 to the usual chemotherapy and bevacizumab (BEV) treatment for ovarian cancer. Research has shown that in earlier studies, patients who received IMNN-001 lived about 13 months longer overall and had 3 more months without cancer progression compared to those who only had the standard treatment. IMNN-001 also appears to improve the area around the tumor, potentially extending patient survival. These results suggest that IMNN-001 could be a valuable addition to current treatments for advanced ovarian cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Amir Jazaeri, MD

Principal Investigator

University of Texas MD Anderson Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced ovarian, fallopian tube, or primary peritoneal cancer at FIGO stage III or IV. They must be recommended for neoadjuvant therapy and have high grade serous adenocarcinoma confirmed by laparoscopy. Participants need proper organ function, no severe illnesses including recent COVID-19, no hormonal cancer therapies within a week before the trial starts, and an ECOG performance status of 0-1. Women must not be pregnant or breastfeeding and agree to use contraception.

Inclusion Criteria

I haven't had a serious illness, infection needing strong antibiotics, or COVID-19 in the last 4 weeks.

My ovarian cancer is a specific type called high grade serous adenocarcinoma.

I am suspected to have advanced ovarian, fallopian tube, or peritoneal cancer, awaiting confirmation via laparoscopy.

Exclusion Criteria

I haven't had radiation in my abdomen or pelvis but may have had it for breast, head and neck, or skin cancer over three years ago without recurrence.

Subjects who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to IMNN-001 or other drugs used in this study

I have previously been treated with IMNN-001.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive neoadjuvant chemotherapy with Paclitaxel and Carboplatin every 21 days for 4 to 6 cycles, with BEV included in certain cycles.

12-18 weeks

Interval Cytoreductive Surgery (ICS)

Interval cytoreductive surgery is performed 3-4 weeks after the last dose of neoadjuvant chemotherapy.

3-4 weeks

Adjuvant Chemotherapy

Participants receive adjuvant chemotherapy with Paclitaxel and Carboplatin, with BEV included in certain cycles, for 3 additional cycles.

9 weeks

Maintenance Therapy

BEV is administered every 3 weeks as a single agent until disease progression or unacceptable toxicity, for up to an additional 18 cycles.

54 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment.

8 months

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Carboplatin
• GEN1
• Paclitaxel

Trial Overview

The study tests adding IMNN-001 (GEN-1) to standard chemotherapy with Bevacizumab versus chemotherapy with Bevacizumab alone in patients with newly diagnosed advanced ovarian-related cancers. It's a phase I/II randomized open-label trial assessing safety, dosing efficacy, and biological activity.

How Is the Trial Designed?

Group I: Chemotherapy + BEV + IMNN-001 (Experimental) Experimental Treatment 4 Interventions

Chemotherapy (neoadjuvant and adjuvant): Paclitaxel 175 mg/m2 IV followed by carboplatin AUC 5-6 IV starting on C1D1. During the neoadjuvant period, there will be from 4 to 6 cycles repeated every 21 days. BEV 15 mg/kg IV administration will be included with each cycle except during the cycles around time of surgery. During maintenance, BEV will be administered every 3 weeks as a single agent until disease progression or unacceptable toxicity for a maximum of an additional 18 cycles. In total, BEV may be administered up to 24 cycles. FDA approved BEV biosimilars may be used in this study in place of BEV. IMNN-001 80 mg/m2 IP will be administered weekly beginning C1D15 and continue weekly through the last cycle of adjuvant therapy. At the conclusion of chemotherapy, GEN-1 will be administered every 21 days with BEV in subjects who are BRCA-/HRP until disease progression or unacceptable toxicity for up to an additional 18 cycles.

Group II: Chemotherapy + BEV (Control) Experimental Treatment 3 Interventions

Chemotherapy (neoadjuvant and adjuvant): Paclitaxel 175 mg/m2 IV followed by carboplatin AUC 5-6 IV starting on C1D1. During the neoadjuvant period, there will be from 4 to 6 cycles (at the Investigator's discretion, having an additional C4+1 and C4+2) repeated every 21 days. BEV 15 mg/kg IV administration will be included with each cycle EXCEPT the following cycles: \[1\] Cycle 1, \[2\] the last cycle of neoadjuvant therapy immediately preceding ICS, and \[3\] the first cycle of adjuvant chemotherapy (i.e., first cycle after ICS). During the maintenance phase, BEV 15 mg/kg will be administered every 3 weeks as a single agent until disease progression or unacceptable toxicity for a maximum of an additional 18 cycles. In total, BEV may be administered up to 24 cycles. FDA approved BEV biosimilars may be used in this study in place of BEV.

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

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

Imunon

Lead Sponsor

Trials

16

Recruited

1,600+

Breakthrough Cancer Research

Collaborator

Trials

2

Recruited

250+

Break Through Cancer Foundation

Collaborator

Trials

1

Recruited

50+

Published Research Related to This Trial

Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor-A, has shown response rates of 16-21% as a single-agent treatment for recurrent ovarian cancer, indicating its efficacy in this context.

In combination with standard chemotherapy for advanced ovarian cancer, bevacizumab significantly improves progression-free survival, although it does not enhance overall survival; the main safety concern is hypertension, with rare but serious risks including gastrointestinal perforation and toxicity to the kidneys and central nervous system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab and ovarian cancer. Garcia, A., Singh, H.[2021]

Bevacizumab, a monoclonal antibody that targets VEGF, has shown anticancer activity in ovarian cancer, both as a single agent and in combination with chemotherapy, leading to its FDA approval for several cancers.

While bevacizumab can be effective, there is a significant risk of gastrointestinal perforation, especially in patients who have been heavily pretreated, which is an important consideration for patients and healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab and its use in epithelial ovarian cancer. Matulonis, UA.[2019]

In a study involving 35 patients with advanced ovarian cancer, the combination of bevacizumab with carboplatin and paclitaxel resulted in a median progression-free survival of 20 months, indicating its efficacy as a first-line treatment.

The study suggests that bevacizumab, administered for over 7.5 months in 70% of patients, should be considered a standard treatment option for advanced ovarian cancer based on its positive impact on progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab with Chemotherapy as a First-Line Treatment for Advanced Ovarian Cancer in a Serbian Cohort. Conic, I., Nedovic, B., Stojnev, S., et al.[2023]

Bevacizumab, an anti-VEGF therapy, has shown efficacy in treating epithelial ovarian cancers, both as a standalone treatment and in combination with other therapies, based on evidence from Phase II trials involving various patient populations.

While most side effects of bevacizumab, such as proteinuria and hypertension, are mild and manageable, there are serious but rare risks like arterial thromboembolism and gastrointestinal perforation, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with bevacizumab in the management of epithelial ovarian cancer. Burger, RA.[2015]

In a study of 100 patients with refractory and platinum-resistant epithelial ovarian cancer, paclitaxel treatment resulted in a 25% response rate, with some patients achieving complete responses after six cycles.

Paclitaxel was generally well tolerated, although there were serious adverse events in a few patients, such as bowel perforation or fistula, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol) treatment for refractory ovarian cancer: phase II clinical trial. Seewaldt, VL., Greer, BE., Cain, JM., et al.[2019]

In a study of 90 ovarian cancer patients, the combination of bevacizumab with paclitaxel and carboplatin significantly improved treatment outcomes, with higher remission and disease control rates compared to those receiving only paclitaxel and carboplatin.

The combined treatment also led to lower levels of tumor markers CA199, CEA, and CA242 without increasing the risk of adverse effects, indicating it is a safe and effective option for improving patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of bevacizumab plus paclitaxel and carboplatin regimen on prognostic survival of ovarian cancer patients. Jiang, Q., Qian, H., Mei, L., et al.[2023]

Bevacizumab, when combined with carboplatin and paclitaxel, significantly prolongs progression-free survival in women with newly diagnosed advanced ovarian cancer, as shown in the GOG-0218 and ICON7 studies.

In patients with recurrent platinum-sensitive ovarian cancer, bevacizumab combined with carboplatin and gemcitabine also extends progression-free survival, demonstrating its efficacy in both first-line and second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab combination therapy: a review of its use in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. Dhillon, S.[2019]

In a study of 114 patients with advanced ovarian cancer treated with carboplatin, paclitaxel, and bevacizumab, 41% experienced arthralgia (joint pain), indicating it is a common side effect of this treatment.

Although patients with arthralgia had a median progression-free survival of 29 months compared to 18 months for those without, this difference was not statistically significant when accounting for other factors, suggesting that while arthralgia is prevalent, it may not directly impact long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Arthralgia in patients with ovarian cancer treated with bevacizumab and chemotherapy. Ventriglia, J., Paciolla, I., Pisano, C., et al.[2021]

Combining Bevacizumab (Bev) with standard chemotherapy significantly improves progression-free survival (PFS) and overall survival (OS) in newly diagnosed ovarian cancer patients, with a notable effect size (HR for OS of 0.87) based on data from 2 trials involving 2776 patients.

While both doses of Bev (7.5 mg/kg and 15 mg/kg) showed similar efficacy in PFS and OS, the higher dose was associated with increased toxicities, suggesting that the lower dose may be the safer and more optimal choice for patients at high risk for disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III trials of standard chemotherapy with or without bevacizumab for ovarian cancer: a meta-analysis. Zhou, M., Yu, P., Qu, X., et al.[2021]

In a multicenter study involving elderly patients (70 years and older) with FIGO stage IV ovarian cancer, the combination of bevacizumab with carboplatin and paclitaxel showed a progression-free survival of 14.5 months, indicating its effectiveness in this age group.

The treatment was generally safe, with common adverse events including hypertension (55%), epistaxis (32%), and proteinuria (21%), but no new safety concerns were identified, suggesting that age alone should not be a barrier to treatment for advanced ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective non-interventional BELOVA/BGOG-ov16 study on safety of frontline bevacizumab in elderly patients with FIGO stage IV ovarian cancer: a study of the Belgian and Luxembourg Gynaecological Oncology Group. Vergote, I., Van Nieuwenhuysen, E., De Waele, S., et al.[2022]

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]

Bevacizumab (Avastin) has been approved for use in combination with other therapies for patients with platinum-resistant ovarian cancer, showing antitumor activity in this challenging setting.

Despite the overall low response rates (around 10%) to treatments for platinum-resistant ovarian cancer, bevacizumab is currently the most studied antiangiogenic therapy, with ongoing research into alternative treatments like tyrosine kinase inhibitors and angiopoietin inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of bevacizumab in the treatment of platinum-resistant ovarian cancer: current perspectives. McClung, EC., Wenham, RM.[2022]

In a phase 3 trial involving 682 patients with recurrent ovarian cancer, the combination of carboplatin-pegylated liposomal doxorubicin and bevacizumab showed a median progression-free survival of 13.3 months, significantly longer than the 11.6 months observed with the standard carboplatin-gemcitabine-bevacizumab regimen (p=0.012).

The safety profile was comparable between the two treatment groups, with hypertension and neutropenia being the most common severe adverse events; however, treatment-related deaths were rare, occurring in less than 1% of patients in both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. Pfisterer, J., Shannon, CM., Baumann, K., et al.[2022]

In a study of 299 patients with advanced ovarian cancer, combining bevacizumab with carboplatin/paclitaxel resulted in a median progression-free survival of 15.4 months, indicating its efficacy as a front-line treatment.

The treatment was generally safe, with 54% of patients experiencing grade 3/4 adverse events, primarily hypertension and neutropenia, and a 1-year overall survival rate of 94%, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of front-line bevacizumab in advanced ovarian cancer: the OSCAR study. Hall, M., Bertelli, G., Li, L., et al.[2020]

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