Cerulean Pharma, Inc. is developing CRLX101, an investigational NDC with a camptothecin payload. CRLX101 has been investigated in more than 350 pts as monotherapy or in combination with bevacizumab in pts with renal cell carcinoma (Keefe, ASCO 2015, abstract #4543) and platinum-refractory OC (Krasner, ASCO 2014, abstract #5581). Preclinical and early clinical data suggest synergy between taxanes and topoisomerase 1 inhibitors. We started a Phase 1b trial for this combination in pts with platinum-resistant OC.
Cohorts of 3 pts were accrued in this trial. Two dose levels of CRLX101 (every other week) in combination with weekly [wkly] paclitaxel 80 mg/m2 (3 wks on/1 wk off) were planned: dose level 1, CRLX101 12 mg/m2; dose level 2, CRLX101 15 mg/m2 . The primary objective was to determine the maximum tolerated dose of CRLX101 in combination with wkly paclitaxel. Secondary objectives included pharmacokinetics, safety, tolerability, and clinical activity.
As of March 11, 2016, 9 pts have been enrolled and treated at dose levels 1 (n = 3) and 2 (n = 6); all pts were evaluable for safety and response. Median age was 61 years (range, 49–73); median number of previous regimens was 3 (range, 1–4). GOG score performance status was 0 (6 pts) or 1 (3 pts). No dose-limiting toxicities have been reported at either dose level, thus the RP2D is CRLX101 15 mg/m2 (every other week) and paclitaxel 80 mg/m2 (3 weeks on/1 week off). Treatment-related adverse events (AEs) included fatigue (6/9, 67%), neutrophil count decreased (4/9, 44%), nausea (4/9, 44%), vomiting, alopecia, headache, infusion-related reaction, and urinary tract infection (2/9, 22% for all). The only grade ≥3 treatment-related AE was neutropenia, which occurred in 2 pts (1 grade 3; 1 grade 4). Partial response and stable disease rates were 56% (5/9) and 11% (1/9), respectively. Moreover, CA125 responses (≥50% decline from baseline) were demonstrated in 33% (3/9) of pts. Two pts (at 15 mg/m2) are still receiving therapy.
CRLX101 given every other wk in combination with wkly paclitaxel has demonstrated early signs of antitumor activity and has been generally well tolerated to date in pts with platinum-resistant OC.
Clinical trial identification
Legal entity responsible for the study
Cerulean Pharma, Inc.
Cerulean Pharma, Inc.
R.J. Schilder: reports personal fees from Millennium, Clovis, MedImmune and Merck Serrano. D. O'Malley: reports personal fees from Clovis, Janssen, AstraZeneca, Genentech/Roche, Eisai and Clovis. J. Li, W. Downing, A. Senderowicz: is an employee of Cerulean Pharma, Inc. All other authors have declared no conflicts of interest.