Ovarian cancer remains one of the most aggressive gynecological malignancies. Traditional, platinum-based chemotherapy is the standard frontline treatment providing initial benefit for the majority of patients. However, the challenge of ovarian tumors being refractory or becoming resistant to platinum has continued to thwart long-term therapeutic success.
As the leading cause of death among gynecological cancers, the need for new and progressive treatments for ovarian cancer is urgent.
Enter Genelux Corporation — a biopharmaceutical company that is developing an innovative approach in hopes of addressing this high unmet medical need. Its therapy offers a potential option for patients struggling with platinum-resistant/refractory ovarian cancer (PRROC).
The challenge of platinum resistance or refractoriness
Platinum-based chemotherapies, such as cisplatin and carboplatin, are integral in treating ovarian cancer. These drugs work by damaging the DNA of cancer cells, which prevents them from dividing and growing.
Initially, many patients respond well to these treatments, but over time, cancer cells can develop resistance or refractoriness to chemotherapy. This platinum resistance/refractoriness occurs in over 70% of patients with advanced ovarian cancer, severely limiting the effectiveness of subsequent line(s) of platinum-based treatments, as well as to other cytotoxic chemotherapies. Once resistance develops, the prognosis becomes poor, with few options left for patients.
Platinum resensitization aims to remodel the tumor microenvironment of cancer cells to be responsive to platinum-based chemotherapy, which is a long-sought-after goal and has been referred to as the “Holy Grail” of gynecologic oncologists. This is where Genelux’s approach has shown significant promise, offering a new strategy to (re-)sensitize cancer cells to platinum-based therapies.
Genelux’s innovative approach: Oncolytic immunotherapy
Genelux Corporation is at the forefront of developing oncolytic immunotherapies. Its lead candidate, olvimulogene nanivacirepvec (Olvi-Vec), is a proprietary, modified strain of the vaccinia virus, which is not a natural human pathogen and is designed to kill cancer cells while sparing healthy tissue.
This novel therapy not only directly attacks cancer cells but, in doing so, also stimulates the immune system to recognize and destroy tumors, and alters the tumor to potentially make it more susceptible to other therapies, offering a three-pronged approach to treatment.
One of the most promising aspects of Olvi-Vec is its potential to overcome ovarian tumor insensitivity to platinum-based chemotherapy. In clinical studies, Olvi-Vec has been shown to disrupt the cellular mechanisms that cancer cells use to evade the effects of platinum-based chemotherapy. In some patients, this disruption may allow previously resistant/refractory cancer cells to become susceptible to platinum drugs once again.
Click here for more information about joining a Phase 3 clinical trial for Olvi-Vec
Clinical trials and future directions
In a Phase 2 trial (VIRO-15), heavily pre-treated patients, with a median of four prior lines of therapy, received Olvi-Vec-primed immunochemotherapy. The results of the trial provided evidence that patients previously deemed platinum-resistant or -refractory demonstrated responsiveness to platinum-based therapy, and were observed to have achieved sustained and clinically meaningful benefit following treatment.[1]
Based on the positive results from the VIRO-15 Phase 2 trial, a Phase 3 registration trial (OnPrime) is currently enrolling patients at clinical sites throughout the United States without regard to their biomarker status or refractory tumor status, and without placing a cap on the number of prior lines of therapy. This trial is designed to demonstrate the benefit of Olvi-Vec by clinical reversal of platinum-resistance or refractoriness in PRROC patients.
Broader applications
The potential impact of Genelux’s novel virotherapy could extend beyond late-stage ovarian cancer. Olvi-Vec as a resensitizing agent to chemotherapies through its immune modulating functions could potentially open the door to new treatment paradigms in earlier stages of ovarian cancer and other cancers that have developed resistance to standard therapies, which could offer renewed hope to patients with limited treatment options.
Click here for more information about the OnPrime clinical trial
[1]Holloway WH, Mendivil AA, Kendrick JE, Abaid LN, Brown JV, LeBlanc J, McKenzie ND, Mori KM, Ahmad S. “Clinical Activity of Olvimulogene Nanivacirepvec–Primed Immunochemotherapy in Heavily Pretreated Patients With Platinum-Resistant or Platinum-Refractory Ovarian Cancer — The Nonrandomized Phase 2 VIRO-15 Clinical Trial.” JAMA Oncology, https://genelux.com/wp-content/uploads/2024/04/2023-Holloway-RW-et-al-JAMA-Oncol-Phase-2-clinical-data-M.pdf.
