Abstract CT151: A Phase II study of NLG207 (formerly CRLX101) in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer
Authors: Duska Linda , O'Malley David M. , Krasner Carolyn , Schilder Russell J. , Mathews Cara , Moore Kathleen , Thaker Premal , Miller Austin , Purdy Christopher , Leyco A.J. , Smith Christopher , Mercier Deborah , Tennant Lucinda , Kennedy Eugene , Vahanian Nicholas , Link Charles 
Published: August 2019

Abstract
Background: NLG207 (formerly CRLX101) is an investigational nanoparticle-drug conjugate (NDC) composed of a cyclodextrin-based polymer backbone linked to camptothecin, a topoisomerase-1 inhibitor. NDCs enhance drug delivery to tumors where gradual payload release inside cancer cells augments antitumor activity while reducing toxicity. The RP2D of CRLX101 was previously set at 15 mg/m2 Q2W in combination with 80 mg/m2 weekly paclitaxel in Phase I and reported at ESMO 2016. This abstract will include data from both the Phase Ib and the phase II expansion.
Methods: In this Phase II single arm study, patients were treated with NLG207 (Q2W) and 80 mg/m2 paclitaxel (3 wks on/1 wk off) repeated q 28 days until progression or toxicity. Primary objective was overall response (CR + PR) via RECIST v1.1 in women with recurrent platinum resistant epithelial ovarian, fallopian tube or primary peritoneal cancer. Progression free survival (PFS), duration of response (DOR), and safety were also assessed.
Results: Thirty patients were enrolled and all completed at least one cycle. Median age was 62 (44-76) years. 57% of patients received ≥3 prior therapies. There were 8/30 confirmed responses for an overall response rate (ORR) of 26.7% (95% CI 14.2%, 44.4%), including one complete response (CR). ORR for platinum resistant patients (n=17) was 23.5% (4/17) vs. 30.8% (4/13) for those who were platinum sensitive (n=13) to their most recent platinum regimen. Best response (including unconfirmed) for platinum resistant patients was 41.2% (7/17) including 7 PRs. Five additional platinum resistant patients achieved stable disease (SD). Median PFS (mPFS) for all study patients was 5.4 months. The mPFS was similar for both platinum resistant at 5.5 months and platinum sensitive at 5.4 months. Median DOR was 7.2 months for platinum resistant patients vs. 4.7 months for the platinum sensitive group. The most common grade 3/4 adverse events (AEs) attributed to study treatment were: decreased neutrophil count (13 patients, 43%), anemia (3 patients, 10%), hematuria (2 patients, 7%); urinary tract infection (UTI), cystitis, hypertension, and hypokalemia (all seen in 1 patient, 3%). PK data will be included in the full presentation.
Conclusions: NLG207 is a potentially best-in-class topoisomerase 1 inhibitor with demonstrated antitumor activity in recurrent ovarian cancer including those who have become resistant to platinum therapy. AE profile of this combination is consistent with that seen for paclitaxel as a single agent except for cystitis, hematuria and UTI. It was well-tolerated in combination with weekly paclitaxel in heavily pre-treated patients. NLG207 warrants further investigation in combination therapy regimens for recurrent ovarian, fallopian tube or primary peritoneal cancer, particularly in platinum resistant patients.
Citation Format: Linda Duska, David M. O'Malley, Carolyn Krasner, Russell J. Schilder, Cara Mathews, Kathleen Moore, Premal Thaker, Austin Miller, Christopher Purdy, A.J. Leyco, Christopher Smith, Deborah Mercier, Lucinda Tennant, Eugene Kennedy, Nicholas Vahanian, Charles Link. A Phase II study of NLG207 (formerly CRLX101) in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT151.