Olvi-Vec + Chemotherapy for Ovarian Cancer

(OnPrime Trial)

Recruiting at 33 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Genelux Corporation

Must not be taking: Antivirals, Immunosuppressants, Steroids

Disqualifiers: CNS metastasis, HIV, Hepatitis, others

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

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: 4-5 weeks

186 Participants Needed

Trial Summary

What is the purpose of this trial?

The OnPrime study is a multi-center, randomized open-label phase 3 study evaluating the safety and efficacy of Olvi-Vec followed by platinum-doublet chemotherapy and bevacizumab compared to the Active Comparator Arm with Physician's Choice of chemotherapy and bevacizumab in women diagnosed with platinum-resistant/refractory ovarian cancer (includes fallopian tube cancer and primary peritoneal cancer). This Phase III trial builds on the efficacy and safety data reported in the previous Phase II VIRO-15 trial with promising objective response rate and progression-free survival observed in heavily pre-treated patients with platinum-resistant/refractory ovarian cancer. The phase II results also showed that the intra-peritoneal route of delivery was efficient in generating tumor cell killing and immune activation, and led to clinical reversal of platinum-resistance or refractoriness in this difficult-to-treat patient population.

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 have received chemotherapy, radiotherapy, or other anti-cancer biologic therapies within 4 weeks prior to the planned treatment, or if you are receiving immunosuppressive therapy or steroids above a certain dose.

What data supports the effectiveness of the drug Olvi-Vec + Chemotherapy for Ovarian Cancer?

Research shows that adding bevacizumab (a drug that stops the growth of new blood vessels) to standard chemotherapy can improve the time patients live without their cancer getting worse, although it doesn't increase overall survival. This suggests that combining bevacizumab with chemotherapy might help control ovarian cancer for a longer period. ^{1 2 3 4 5}

Is the combination of Olvi-Vec and chemotherapy safe for treating ovarian cancer?

Bevacizumab, a component of the treatment, has been studied extensively and is generally considered safe for ovarian cancer, though it can cause side effects like high blood pressure, bleeding, and delayed wound healing. These side effects are usually manageable by doctors. The safety of Olvi-Vec specifically is not detailed in the provided research. ^{2 6 7 8 9}

What makes the Olvi-Vec + Chemotherapy treatment for ovarian cancer unique?

The Olvi-Vec + Chemotherapy treatment is unique because it combines a novel oncolytic virus therapy (Olvimulogene Nanivacirepvec) with standard chemotherapy and bevacizumab, potentially offering a new mechanism of action by using a virus to target cancer cells, which is different from traditional chemotherapy or bevacizumab alone. ^{1 4 10 11 12}

Research Team

Robert W. Holloway, MD

Principal Investigator

AdventHealth Cancer Institute

Eligibility Criteria

This trial is for women with ovarian cancer that's resistant to platinum-based treatments. They should have had at least three prior systemic therapies, a life expectancy of over six months, and no major health issues that would interfere with the treatment. Participants must not have had recent surgeries or other cancers in the last three years, among other criteria.

Inclusion Criteria

My cancer did not respond to platinum-based chemotherapy.

My ovarian cancer is of a specific type: high-grade serous, endometrioid, or clear-cell.

I am fully active or can carry out light work.

Exclusion Criteria

I have not had a bowel obstruction in the last 3 months.

I do not have an active infection like a UTI or pneumonia.

I have not had a blood clot in the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants in the Experimental Arm receive Olvi-Vec via intraperitoneal catheter for 2 consecutive days, followed by platinum-doublet chemotherapy and bevacizumab starting in Week 4 or 5. The Control Arm receives Physician's Choice of chemotherapy and bevacizumab starting in Week 0.

4-5 weeks

Multiple visits for infusions and monitoring

Follow-up

Participants are monitored for progression-free survival, safety, and overall survival. Assessments include radiological evaluations and adverse event monitoring.

12 months

Regular visits for assessments

Long-term Follow-up

Continued monitoring for overall survival and long-term safety, with assessments up to 36 months.

36 months

Treatment Details

Interventions

• Bevacizumab
• Carboplatin
• Gemcitabine
• Olvimulogene Nanivacirepvec

Trial Overview The OnPrime study compares Olvi-Vec followed by platinum-doublet chemotherapy and bevacizumab against just platinum-doublet chemotherapy and bevacizumab. It aims to see if adding Olvi-Vec improves outcomes for those with tough-to-treat ovarian cancer.

Participant Groups

Group I: Olvi-Vec + Platinum-doublet & bevacizumab Experimental Treatment 4 Interventions

Olvi-Vec: A total of 2 consecutive days of intraperitoneal catheter infusions in Week 0 Platinum-doublet \& bevacizumab (or biosimilar) administered beginning in Week 4 (preferred), but no later than Week 5

Group II: Physician's Choice of Chemotherapy & bevacizumab Active Control 3 Interventions

Physician's Choice of chemotherapy \& bevacizumab (or biosimilar) administered beginning in Week 0. Physician's Choice of chemotherapy includes either a single agent non-platinum chemotherapy, or as platinum chemotherapy is allowed as an option, a platinum-doublet (i.e., platinum agent combined with a non-platinum agent).

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?

Genelux Corporation

Lead Sponsor

Trials

8

Recruited

460+

GOG Foundation

Collaborator

Trials

48

Recruited

18,500+

Findings from Research

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 phase III trial involving 484 patients with platinum-sensitive recurrent ovarian cancer, the combination of bevacizumab (BV) with gemcitabine and carboplatin (GC) significantly improved progression-free survival (PFS) compared to GC alone, with a median PFS of 12.4 months versus 8.4 months.

The addition of BV also led to a higher objective response rate (78.5% vs. 57.4%) and longer duration of response (10.4 months vs. 7.4 months), although it was associated with increased rates of grade 3 or higher hypertension and proteinuria, indicating a need for monitoring these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. Aghajanian, C., Blank, SV., Goff, BA., et al.[2022]

In a study of 277 patients with recurrent epithelial ovarian cancer, combining chemotherapy with bevacizumab significantly improved progression-free survival (PFS) to 8.7 months compared to 6.7 months with bevacizumab alone.

Overall survival (OS) was also enhanced with the combination treatment, reaching 14.3 months versus 10.5 months for those receiving only bevacizumab, with no significant increase in toxicities between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of bevacizumab alone or with chemotherapy in recurrent ovarian cancer patients. Fuh, KC., Secord, AA., Bevis, KS., et al.[2022]

In a study of 158 patients with platinum-resistant ovarian cancer, gemcitabine was found to be the most effective chemotherapy agent for those with clear cell or mucinous carcinoma, achieving a median time to treatment failure of 5.3 months, while nedaplatin showed the least effectiveness with only 1.4 months.

The efficacy of nedaplatin varied significantly based on the platinum-free interval, showing better outcomes in patients with a platinum-free interval of 3 months or more, highlighting the importance of individual patient characteristics in chemotherapy selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heterogeneous effects of cytotoxic chemotherapies for platinum-resistant ovarian cancer. Nara, K., Taguchi, A., Yamamoto, T., et al.[2023]

The combination treatment of gemcitabine, platinum, and bevacizumab (GPB) showed a high response rate of 78% in 33 patients with recurrent epithelial ovarian cancer, with 48% achieving a complete response and a median progression-free survival of 12 months.

While GPB demonstrated excellent efficacy, it also had serious toxicities, including bowel perforations in 6% of patients and significant hematologic toxicities, indicating that further investigation into its safety profile is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination gemcitabine, platinum, and bevacizumab for the treatment of recurrent ovarian cancer. Richardson, DL., Backes, FJ., Seamon, LG., et al.[2022]

In a study of 46 patients with advanced and recurrent epithelial ovarian cancer treated with bevacizumab and chemotherapy over 30 months, the most common adverse events were hypertension (65.2%) and proteinuria (49%), with hypertension typically occurring 2 months after treatment initiation.

Patients with a history of radiation therapy experienced a significantly higher risk of gastrointestinal perforation, indicating that careful consideration is needed when administering bevacizumab to these individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events Associated With Long-term Treatment of Epithelial Ovarian Cancer With Bevacizumab and Chemotherapy. Yokoyama, Y., Kubo-Kaneda, M., Sunada, K., et al.[2022]

Bevacizumab, a targeted therapy for ovarian cancer, has shown significant improvement in progression-free survival when combined with standard chemotherapy, although it does not extend overall survival.

While bevacizumab can lead to adverse effects like hypertension and bleeding, these can generally be managed effectively, and the treatment has been approved in Europe and the U.S. for its benefits, including improved quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical appraisal of bevacizumab in the treatment of ovarian cancer. Yoshida, H., Yabuno, A., Fujiwara, K.[2018]

In a study of 15 heavily pre-treated ovarian cancer patients, bevacizumab demonstrated a tolerable safety profile, with no gastrointestinal perforations observed, which is a significant concern in previous studies.

The treatment resulted in a partial response in 13.3% of patients and stable disease in 40%, with a median overall survival of 15 months, suggesting that bevacizumab may be an effective option for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in heavily pre-treated and platinum resistant ovarian cancer: a retrospective study of the North-Eastern German Society of Gynaecologic Oncology (NOGGO) Ovarian Cancer Study Group. Pietzner, K., Richter, R., Chekerov, R., et al.[2022]

In a study of 83 women with recurrent gynecologic malignancy, retreatment with bevacizumab (Bev) showed a 26% response rate without significantly increasing toxicity, indicating it can be a safe option for patients who have previously received the drug.

Patients who had a Bev-free interval of more than 9 months before retreatment experienced a significant overall survival advantage, suggesting that timing of retreatment may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retreatment with bevacizumab in patients with gynecologic malignancy is associated with clinical response and does not increase morbidity. Laskey, RA., Richard, SD., Smith, AL., et al.[2021]

In a phase III trial involving 614 patients with recurrent ovarian cancer, the addition of atezolizumab to standard chemotherapy and bevacizumab did not significantly improve progression-free survival (PFS) compared to placebo, indicating limited efficacy in this treatment combination.

Although the overall survival (OS) data showed a trend towards improvement with atezolizumab, it did not reach statistical significance, and both treatment groups experienced a high rate of grade ≥3 adverse events, suggesting that while atezolizumab may have some benefits, its safety profile remains a concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial. Kurtz, JE., Pujade-Lauraine, E., Oaknin, A., et al.[2023]

In a phase III trial involving 361 patients with platinum-resistant ovarian cancer, adding bevacizumab to chemotherapy significantly improved progression-free survival (PFS) from 3.4 months to 6.7 months and increased the objective response rate (ORR) from 11.8% to 27.3%.

While the overall survival (OS) showed a trend favoring bevacizumab, it was not statistically significant, and the treatment was associated with increased risks of grade ≥ 2 hypertension and proteinuria, with a small incidence of gastrointestinal perforation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. Pujade-Lauraine, E., Hilpert, F., Weber, B., et al.[2022]

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]

References

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

Phase III trials of standard chemotherapy with or without bevacizumab for ovarian cancer: a meta-analysis. [2021]

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

OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. [2022]

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

Comparison of bevacizumab alone or with chemotherapy in recurrent ovarian cancer patients. [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

Heterogeneous effects of cytotoxic chemotherapies for platinum-resistant ovarian cancer. [2023]

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

Combination gemcitabine, platinum, and bevacizumab for the treatment of recurrent ovarian cancer. [2022]

6. Greece pubmed.ncbi.nlm.nih.gov

Adverse Events Associated With Long-term Treatment of Epithelial Ovarian Cancer With Bevacizumab and Chemotherapy. [2022]

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

Critical appraisal of bevacizumab in the treatment of ovarian cancer. [2018]

8. Greece pubmed.ncbi.nlm.nih.gov

Bevacizumab in heavily pre-treated and platinum resistant ovarian cancer: a retrospective study of the North-Eastern German Society of Gynaecologic Oncology (NOGGO) Ovarian Cancer Study Group. [2022]

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

Retreatment with bevacizumab in patients with gynecologic malignancy is associated with clinical response and does not increase morbidity. [2021]

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

Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial. [2023]

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

Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. [2022]

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

Profile of bevacizumab in the treatment of platinum-resistant ovarian cancer: current perspectives. [2022]