An independent data monitoring committee has recommended that the phase 3 INNOVATE-3 trial exploring the safety and efficacy of tumor treating fields in combination with paclitaxel in patients with platinum-resistant ovarian cancer proceed to the final analysis.
An independent data monitoring committee (DMC) has recommended that the phase 3 INNOVATE-3 trial (ENGOT-ov50; NCT03940196) exploring the safety and efficacy of tumor treating fields (TTFields) in combination with paclitaxel in patients with platinum-resistant ovarian cancer proceed to the final analysis, according to an announcement from Novocure.1
The recommendation follows a review of safety findings for all the patients enrolled to the trial, and an analysis of overall survival (OS) that was done on the first 540 patients who underwent randomization. Data from the prespecified interim analysis of the trial did not signal for a need to increase the sample size, and so the trial will continue as planned.
“Completion of the DMC interim analysis represents the next milestone in our journey to address the significant unmet need for patients diagnosed with platinum-resistant ovarian cancer,” Ely Benaim, MD, chief medical officer of Novocure, stated in a press release. “I would like to thank our investigators and collaborators, ENGOT and The GOG Foundation, as well as our patients for their passion and bravery. We look forward to reviewing final data next year.”
TTFields are electric fields that disturb cancer cell division. These fields can hinder electrically charged cellular components of cancer cells and disrupt their function, which could result in cell death.2 With this approach, cancer cell division can either be slowed down or stopped. Utilizing the investigational medical device referred to as NovoTTF-200(O), the fields are delivered to the region of the body where the tumor is located.
The pivotal, open-label, phase 3 INNOVATE trial enrolled patients with a histologically confirmed diagnosis of ovarian carcinoma that has been unresponsive to therapy containing platinum within 6 months of their last treatment, who are at least 18 years of age and have a life expectancy of at least 12 weeks. Patients needed to be amenable to receive weekly paclitaxel and be able to operate the NovoTTF-200(O) device.
If patients had a history of disease progression on a weekly paclitaxel regimen, had their cancer spread to their brain, an albumin level of less than 25 g/L, grade 3 or higher neuropathy, known allergies to medical adhesives or hydrogel, known reaction to paclitaxel or drugs comparable to paclitaxel, or had prior cancers treated for recurrence within 2 years except for completely resected non-melanomatous skin carcinoma, they were excluded.
Other exclusion criteria included having serious comorbidities, were receiving concurrent antitumor therapy beyond weekly paclitaxel or concurrent active treatment in another study.
Study participants were randomized to receive either weekly paclitaxel alone or weekly paclitaxel concomitantly with TTFields tuned to 200 kHz until disease progression.
The primary end point of the trial is OS, and key secondary end points include progression-free survival (PFS), objective response rate, severity and frequency of adverse effects, time to deterioration in health-related quality of life (QOL) or death, and QOL.
As of October 2021, the study has accrued a total of 540 patients. Data from the trial are anticipated to be reviewed in 2023, after an 18-month follow-up period.
Previously, TTFields in combination with weekly paclitaxel was observed in patients with platinum-resistant ovarian cancer as part of the single-arm, phase 2 INNOVATE trial (NCT02244502).3
A total of 31 patients were enrolled to the trial. Study participants received TTFields given at 200 kHz in conjunction with paclitaxel given weekly for 8 weeks and then on days 1, 8, 16 of each subsequent 28-day cycle, with a starting dose of 80 mg/m2.
The median age among study participants was 60 years, and 77% had serous histology and stage III disease. All participants previously received platinum-based chemotherapy. Ninety-seven percent of patients received prior taxanes, and 58% received pegylated liposomal doxorubicin. The primary end point of the trial was safety.
Additional data showed that the 1-year survival rate with the combination was 61% (95% CI, 37%-78%), and the clinical benefit rate was 71%. Seven patients experienced partial responses with the treatment and 13 patients achieved stable disease. The median PFS was 8.9 months (95% CI, 4.3–not reached).
No serious adverse effects (AEs) were experienced with TTFields, and combination with paclitaxel was found to be well tolerated. Ninety percent of patients experienced dermatologic AEs. Two patients reported grade 3 dermatitis, 1 of whom discontinued treatment because of the toxicity. Fifty-five percent of patients experienced grade 3 or 4 toxicities with the combination, and most of these effects were blood and lymphatic system disorders (n = 9), anemia (n = 4), and neutropenia (n = 3).