Phase 3 IMagyn050 Trial in Ovarian Cancer Does Not Meet Primary End Point of PFS

Levi Garraway, MD, PhD

Results from the phase 3 IMagyn050 trial showed that the addition of atezolizumab (Tecentriq) to bevacizumab (Avastin), paclitaxel, and carboplatin did not meet the primary end point of progression-free survival (PFS) for first-line treatment of women with newly diagnosed, advanced ovarian cancer, according to Roche, the developer of atezolizumab.¹

“Ovarian cancer remains one of the most aggressive cancers and is difficult to treat in its advanced stages,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, said in a recent press release. “While we are disappointed by these results, we remain committed to improving outcomes for women living with this disease and are pleased that Avastin remains a key component in the treatment of front-line ovarian cancer.”

Topline data demonstrated that the safety for the atezolizumab combination proved to be consistent with what has previously been reported with the regimen. Data for the overall survival (OS) co-primary end point of the trial remain immature at this time. Follow-up for this end point will continue until the next planned analysis, according to Roche.

In the multicenter, double-blind, phase 3 trial, investigators evaluated the safety and efficacy of atezolizumab plus bevacizumab, paclitaxel, and carboplatin versus bevacizumab, paclitaxel, and carboplatin alone in women with stage III or IV ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with macroscopic residual disease postoperatively or who will undergo neoadjuvant therapy followed by interval surgery.²

In order to be eligible for enrollment on the trial, patients had to have an ECOG performance status ranging from 0-2 and a life expectancy of greater than 12 weeks. For those who received therapeutic anticoagulation, they had to have had a stable anticoagulant regimen. Patients also had to have a representative formalin-fixed, paraffin-embedded tumor specimen in paraffin blocks available, or at least 20 unstained slides.

Those who had been diagnosed with borderline epithelial ovarian tumor, who had recurrent invasive epithelial ovarian, fallopian tube, or primary peritoneal cancer that had only been treated with surgery, or who had non-epithelial ovarian disease were not eligible for enrollment. If patients received prior radiotherapy to any portion of the abdominal cavity or pelvis, prior chemotherapy for abdominal or pelvic disease, or any biological and/or targeted therapy, they could not enroll on the trial.

In the experimental arm, those in the primary tumor-reductive surgery group received paclitaxel, carboplatin, and atezolizumab via intravenous (IV) infusion on day 1 of each 21-day treatment cycle for the duration of 6 cycles. Starting with cycle 2, they received IV bevacizumab for a total of 5 cycles, followed by maintenance therapy with atezolizumab plus bevacizumab; in total, they received 22 cycles of atezolizumab and 21 cycles of bevacizumab. Those in the neoadjuvant group received atezolizumab plus paclitaxel and carboplatin for 6 treatment cycles and bevacizumab for 4 cycles. Interval surgery was conducted between cycles 3 and 4. After 6 cycles, patients started maintenance therapy comprised of atezolizumab plus bevacizumab for an additional 16 cycles.

In the placebo arm, patients in the primary tumor-reductive surgery group were given paclitaxel, carboplatin, and placebo via IV infusion on day 1 of each 21-day treatment cycle for 6 total cycles, and bevacizumab IV infusion starting with cycle 2 for 5 total cycles. This was followed by maintenance treatment comprised of bevacizumab plus placebo; patients received a total of 22 cycles of placebo and 21 cycles of bevacizumab. Those in the neoadjuvant group received paclitaxel and carboplatin plus placebo for 6 treatment cycles and bevacizumab for 4 cycles.

The primary end points of the trial included PFS as assessed by investigator per RECIST v1.1 criteria in the intent-to-treat (ITT) population; PFS as assessed by investigator via RECIST v1.1 criteria in the PD-L1–positive subgroup; OS in the ITT population; and OS in the PD-L1–positive population. Secondary end points included the percentage of patients with objective response as assessed by investigator per RECIST v1.1 criteria; investigator-assessed duration of response per RECIST v1.1 criteria; the percentage of patients who achieved a clinically meaningful improvement in patient-reported abdominal pain or bloating in the neoadjuvant group; among others.

The trial will undergo further examination to strengthen the gynecologic development program for atezolizumab.

“The Tecentriq program in ovarian cancer and cervical cancers builds on the combination with Avastin, which has helped women with newly diagnosed, advanced or relapsed ovarian and cervical cancers live without their disease getting worse, as demonstrated in results across 7 pivotal phase 3 trials that involved more than 5,000 women,” according to Roche.

In December 2018, the FDA approved atezolizumab in combination with bevacizumab, paclitaxel, and carboplatin for use in the frontline treatment of patients with metastatic nonsquamous, non–small cell lung cancer without EGFR or ALK tumor aberrations.

References

1. Roche provides update on phase III study of Tecentriq in women with advanced stage ovarian cancer. News release. Roche. July 13, 2020. Accessed July 13, 2020. bit.ly/2CsVGpV.
2. A study of atezolizumab versus placebo in combination with paclitaxel, carboplatin, and bevacizumab in participants with newly-diagnosed stage III or stage IV ovarian, fallopian tube, or primary peritoneal cancer (IMagyn050). ClinicalTrials.gov. Updated July 8, 2020. Accessed July 13, 2020. https://clinicaltrials.gov/ct2/show/NCT03038100.