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Poster display

1781 - Evaluation of weekly dosing of CRLX101 alone and in combination with bevacizumab (bev) in patients (pts) with advanced solid tumors


10 Oct 2016


Poster display


Nehal Lakhani


Annals of Oncology (2016) 27 (6): 114-135. 10.1093/annonc/mdw368


N. Lakhani1, S.A. Piha-Paul2, A. Senderowicz3, K. Caliri3, T. Crowell3, H. Wang4, A. Tolcher5

Author affiliations

  • 1 Clinical Research, START Midwest/Cancer & Hematology Centers of Western Michigan, PC, 49503 - Grand Rapids/US
  • 2 Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 77030 - Houston/US
  • 3 Clinical Operations, Cerulean Pharma, Inc., 02451-1215 - Waltham/US
  • 4 Research, Cerulean Pharma, Inc., 02451-1215 - Waltham/US
  • 5 Clinical Research, START - South Texas Accelerated Research Therapeutics, LLC, 78229 - San Antonio/US


Abstract 1781


CRLX101, a novel investigational nanoparticle-drug conjugate containing camptothecin, is a dual inhibitor of topoisomerase I and hypoxia-inducible factors 1α and 2α. The maximum tolerated dose (MTD) from the first-in- human study is 15 mg/m2 biweekly (QOW; Weiss, 2013. Invest New Drugs. 31:986), used clinically in combination with bev in several tumor types. This study is exploring the tolerability of weekly (QW) dosing of CRLX101.


CRLX101 QW (12 mg/m2 or 15 mg/m2) alone (arm 1) or in combination with bev QOW (10 mg/kg, arm 2) was evaluated. Primary objective: MTD of each arm. Secondary objectives: safety and antitumor activity.


As of Apr 7, 2016, the most commonly reported AEs (all grades [gr]) for arm 1 (n = 15) and arm 2 (n = 15) were fatigue (46%, 46%), nausea (40%, 46%), vomiting (33%, 33%), constipation (40%, 0%) and cystitis (27%, 33%), respectively. Arm 1 reported 1 dose-limiting toxicity (DLT): gr 3 febrile neutropenia after 4 QW doses at 12 mg /m2. MTD for arm 1: CRLX101 at 15 mg/m2 QW. In arm 2, 3 DLTs were observed in 3 pts: gr 3 cystitis at 12 mg/m2; gr 3 febrile neutropenia after 4 QW doses and prolonged gr 3/4 neutropenia after 2 doses at 15 mg/m2. Urine alkalization with oral or intravenous sodium bicarbonate was implemented to mitigate cystitis. MTD for arm 2: CRLX101 at 15 mg/m2 QW for 3 of 4 weeks in combination with bev QOW. 20 pts were evaluable for antitumor activity with 3 partial responses (PRs): 1 small cell lung cancer pt refractory to cisplatin in arm 1 at 15 mg/m2, 1 rectal cancer pt refractory to irinotecan and 1 renal cell carcinoma (RCC) pt in arm 2 at 12 mg/m2 (61%, 40% and 30% lesion shrinkage, respectively). 10 pts had stable disease with 2 near PRs (>20% but


MTD for CRLX101 QW monotherapy is 15 mg/m2, representing a 100% increase in dose intensity over the QOW MTD. In arm 2, either 12 mg/m2 QW or 15 mg/m2 for 3 of 4 weeks in combination with bev QOW could be the MTD. No new safety concerns were observed except an increase in cystitis in arm 2 for which urine alkalization was implemented to mitigate the risk. PRs were observed in 3 pts. This more dose-intensive CRLX101 schedule will be tested in future combination studies.

Clinical trial identification

NCT02648711 (NIH)

Legal entity responsible for the study

Cerulean Pharma, Inc.


Cerulean Pharma Inc.


N. Lakhani: Non-financial support from Cerulean, during the conduct of the study; non-financial support from Cerulean, Merck,Pfizer, Abbvie,ArQule Pharma, Regeneron Pharma,Novartis, BMS, Foundation Medicine, LAM Therapeutics, Pronai outside the submitted work.A. Senderowicz, K. Caliri, T. Crowell, H. Wang: Employee at Cerulean Pharma Inc.A. Tolcher: Received fees: Bind Therapeutics, Blend Therapeutics, Celator, Decerna, Janssen, Merus, Nanobiotix, Pharmacyclics, Pierre Fabre Medicament, Symphogen, Valent Tech, Heron, J&J, Asana Biosciences, Akebia, Genmab, Mersana, Endocyte, Proximagan, Upsher-Smith.All other authors have declared no conflicts of interest.

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