IDMC Recommends Continuation of PANOVA-3 Trial of TTFields in Unresectable, Locally Advanced Pancreatic Cancer

An independent data monitoring committee (IDMC) has recommended the continuation of the phase 3 PANOVA-3 trial (NCT03377491) evaluating tumor treating fields (TTFields) in combination with nab-paclitaxel (Abraxane) and gemcitabine for the treatment of patients with unresectable, locally advanced pancreatic cancer.¹

The recommendation was based on the IDMC’s review of safety and efficacy data in an interim analysis for all patients enrolled in the trial, which has completed accrual. The IDMC recommended the study proceed to its final analysis.

“Completion of the interim analysis with the [IDMC’s] recommendation to continue PANOVA-3 to completion marks another important step in pursuit of our mission to treat patients with difficult solid tumors of the abdomen,” Asaf Danziger, chief executive officer of Novocure, stated in a news release. “I would like to express my thanks to our patients and investigators. We look forward to reviewing the PANOVA-3 data in 2024 and potentially extending the lives of patients diagnosed with deadly locally advanced pancreatic cancer by treating with our novel therapy, TTFields.”

Previously reported data from the phase 2 PANOVA trial (NCT01971281) showed that concomitant treatment with TTFields with gemcitabine plus nab-paclitaxel produced a median progression-free survival (PFS) of 12.7 months (95% CI, 5.4-not applicable) and a median overall survival (OS) that was not reached (NR) in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma.²

Those findings led to the initiation of the randomized, open-label PANOVA-3 trial, which was designed to enroll 556 adult patients with unresectable, locally advanced pancreatic adenocarcinoma. Patients were required to have an ECOG performance status of 0 to 2 and be amenable for treatment with gemcitabine and nab-paclitaxel.³

Key exclusion criteria included prior palliative surgery or radiation for the tumor, serious comorbidities, and concurrent antitumor therapy beyond gemcitabine and nab-paclitaxel.

Patients were randomly assigned to receive either the combination of nab-paclitaxel and gemcitabine concomitant with TTFields or nab-paclitaxel plus gemcitabine alone. In both arms, 1000 mg/m2 of gemcitabine and 125 mg/m2 of nab-paclitaxel were given on days 1, 8, and 15 of each 28-day cycle. In the experiment arm, TTFields therapy was tuned to 150 kHz. Treatment continued until disease progression.¹

The final patient was enrolled in February 2023, and patients will be followed for a minimum of 18 months.

OS served as the trial’s primary end point. Secondary end points consisted of PFS, local PFS, objective response rate, 1-year OS rate, quality of life, pain-free survival, puncture-free survival, resectability rate, and toxicity.

References

1. Novocure announces favorable independent data monitoring committee recommendation to continue phase 3 PANOVA-3 clinical trial of tumor treating fields therapy in pancreatic cancer. News release. Novocure. July 21, 2023. Accessed July 25, 2023. https://www.novocure.com/novocure-announces-favorable-independent-data-monitoring-committee-recommendation
2. Rivera F, Benavides M, Gallego J, et al. Tumor treating fields in combination with gemcitabine or gemcitabine plus nab-paclitaxel in pancreatic cancer: Results of the PANOVA phase 2 study. Pancreatology. 2019;19(1):64-72. doi:10.1016/j.pan.2018.10.004
3. Effect of tumor treating fields (TTFields, 150 kHz) as front-line treatment of locally-advanced pancreatic adenocarcinoma concomitant with gemcitabine and nab-paclitaxel (PANOVA-3). ClinicalTrials.gov. Updated April 10, 2023. Accessed July 25, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT03377491