The Lynx Group

A Phase 1/2 Study of Chemo-Immunotherapy with Durvalumab and Pegylated Liposomal Doxorubicin (PLD) in Platinum-Resistant Recurrent Ovarian Cancer

Conference Correspondent

Expression of programmed cell death ligand 1 (PD-L1) has been confirmed in human ovarian cancer cells, and preliminary evidence has supported the antitumor activity of anti–PD-1 therapies, like durvalumab, in treating ovarian cancers.1 In a phase 1/2, multicenter, open-label study, O’Cearbhaill and colleagues reported the preliminary safety and efficacy data of treating patients with platinum-resistant recurrent ovarian cancer with durvalumab in combination with standard-of-care pegylated liposomal doxorubicin (PLD).2

This study included a phase 1 3+3 dose escalation, with dose-limiting toxicity evaluated in one 28-day cycle (n = 6-18), and a phase 2 dose-expansion cohort (n = 41). Given that PLD has been reported to have a 6-month progression-free survival (PFS6) of 25%, the sample size of 41 evaluable patients is appropriately powered to test the null hypothesis of a PFS6 rate of ≤25% against the alternative hypothesis of a PFS rate of ≥45% at an alpha level of 0.05 (one-sided). Blood and tumor samples were also collected for assessment of correlative immunologic responses.

As of March 5, 2018, 40 female patients with a median age of 65 years (range, 32-83 years) were enrolled in phase 2 of the study. Each had received at least 1 dose of study therapy (PLD 40 mg/m2 + durvalumab 1500 mg once every 4 weeks) and were included in the safety analyses. The most frequently observed treatment-emergent adverse events (AEs, all causality), occurring in ≥25% of patients, were palmar-plantar erythrodysesthesia syndrome (PPES)/rash, stomatitis, fatigue, abdominal pain, nausea, pyrexia, and vomiting. Grade 3 treatment-related AEs in ≥2 patients included PPES/rash, stomatitis, lymphocyte count decreased, lipase increased, and anemia. As of the cutoff date, 33 patients had reached the time point for PFS6 assessment. Twelve patients were progression-free at 6 months, yielding a PFS6 of 47.7%. The remaining data will mature by July 2018, and further improvement in PFS6 may occur. At 6 months, 30 patients were still alive, resulting in a 6-month overall survival (OS) of 89%; at 12 months, 12 patients were alive (12-month OS, 65%).

The preliminary results reported here suggest that the combination of durvalumab and PLD has a tolerable safety profile and promising efficacy in women with platinum-resistant ovarian cancer. The final PFS6 and other translational end points are pending additional data.


References

  1. Lee J-M, et al. J Clin Oncol. 2017;35:2193-2202.
  2. O’Cearbhaill RE, et al. ESMO 2018. Abstract 945P.

Related Articles


Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: