Phase Ii Trial Of The Ndc Crlx101 In Combination With Bevacizumab In Patients With Platinum-Resistant Ovarian Cancer (Proc)

Background: CRLX101 is an investigational nanoparticle-drug conjugate (NDC) with a camptothecin payload. CRLX101 is a dual inhibitor of topoisomerase 1 and hypoxia inducible factors 1α and 2α (HIF1-α and HIF-2α). CRLX101 is being explored clinically in several tumor types including renal cell carcinoma (RCC) in combination with Avastin®, (Keefe, ASCO 2015, 4543) and platinum-resistant ovarian cancer (PROC) (Krasner ASCO 2014, 5581). The PROC study has a CRLX101 monotherapy arm (Group A) and a combination arm with Avastin (Group B). Group A patients (pts) received CRLX101 at 15mg/m 2 every other week and Group B patients received CRLX101 15 mg/m 2 with Avastin 10 mg/kg every other week until progression or unacceptable toxicity. The primary endpoint for both groups was rate of progression free survival at 6 months (PFS6) using RECIST 1.1 criteria. Secondary endpoints were objective response rate (ORR), PFS, ?50% reduction of CA125 over baseline, and safety. Adverse events (AEs) were assessed by CTCAE v4.0. Pre- and post-treatment tumor biopsies were collected from a cohort of patients in Group A to evaluate relevant PD endpoints, suggesting that CRLX101 is active in PROC. Results: A total of 18 PROC patients were evaluated in Group B. Demographics: Median age of the patient was 59years (range: 46-68). Median number of previous regimens was 2 (range: 1-3), ECOG PS 0 (13 pts) or 1 (5 pts). The PFS6 was demonstrated in 56% pts (10 out of 18). The PR and stable disease (SD) rates were 17% (3 out of 18 pts) and 78% (14 out of 18 pts), respectively. Median progression-free survival is 6.2 months to date. A ? 50% decline in CA125 was demonstrated in 44% pts (8 out of 18). AEs most commonly observed with the combination were nausea (10 pts, 56%), anemia (10 pts, 56%); proteinuria (8 pts, 44%) and fatigue (6 pts, 33%). The majority of AEs were Grade 1. There were only two drug-related AEs Grade ? 3: one patient developed uncomplicated and reversible elevated ALT (grade 3) and another patient had a short-lived decrease in ANC (grade 4). A retrospective analysis for both cohorts, Group A vs. Group B, demonstrated that the combination showed increased antitumor activity: PFS6: 27 vs 56%, mPFS 4.2 vs 6.2 months and CA125: 23 vs 44%. Conclusions: CRLX101 15 mg/m 2 in combination with Avastin 10 mg/kg given every other week demonstrated antitumor activity and was generally well-tolerated in advanced PROC pts. An additional 25 pts will be enrolled in Group B. This combination is currently being explored in an ongoing randomized controlled Phase 2 trial in 3 rd and 4 th line RCC, and is also being tested in combination with weekly paclitaxel in an ongoing Phase 1b trial in PROC. Clinical trial information: NCT01652079 Citation Format: Carolyn Krasner, Michael Birrer, Christian Peters, Lata Jayaraman, Scott Eliasof, Andres Tellez, William Downing, Adrian Senderowicz. Phase II trial of the NDC CRLX101 in combination with bevacizumab in patients with platinum-resistant ovarian cancer (PROC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT090.