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Phase I trial of ribociclib with platinum chemotherapy in recurrent ovarian cancer

Background: New therapeutic combinations to improve the outcome of ovarian cancer patients are clearly needed. Preclinical studies with ribociclib (LEE-011), a CDK4/6 cell cycle checkpoint inhibitor, demonstrate a synergistic effect with platinum chemotherapy and efficacy as a maintenance therapy after chemotherapy. We tested the safety and initial efficacy of ribociclib in combination with platinum-based chemotherapy in recurrent ovarian cancer.

Methods: This phase I trial combined weekly carboplatin and paclitaxel chemotherapy with ribociclib followed by ribociclib maintenance in patients with recurrent platinum-sensitive ovarian cancer. Primary objectives were safety and maximum tolerated dose (MTD) of ribociclib when given with platinum and taxane chemotherapy. Secondary endpoints were response rate (RR) and progression-free survival (PFS).

Results: Thirty-five patients were enrolled. Patients had a mean 2.5 prior lines of chemotherapy, and 51% received prior maintenance therapy with Poly (ADP-ribose) polymerase inhibitors (PARPi) and/or Bevacizumab. The MTD was 400mg. The most common AEs included anemia (82.9%), neutropenia (82.9%), fatigue (82.9%), and nausea (77.1%). Overall RR was 79.3% with a stable disease (SD) rate of 18% resulting in a clinical benefit rate of 96.6%. The PFS was 11.4 months. RR and PFS did not differ based on number of lines of prior chemotherapy or prior maintenance therapy.

Conclusions: This work demonstrates the combination of ribociclib with chemotherapy in ovarian cancer is feasible and safe. With a clinical benefit rate of 97%, this work provides encouraging evidence of clinical efficacy in patients with recurrent platinum-sensitive disease.

Related Products

Cat.No. Product Name Information
S7440 Ribociclib Ribociclib is an orally available, and highly specific inhibitor of CDK4 and CDK6 with IC50 of 10 nM and 39 nM. Phase 3.

Related Targets

CDK