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Pilot trial of CRLX101 in patients (pts) with advanced, chemotherapy-refractory gastroesophageal cancer (GEC)

Chao, Joseph and Lin, James and Frankel, Paul Henry and Clark, Andrew J. and Wiley, Devin T. and Garmey, Edward Graeme and Fakih, Marwan and Lim, Dean and Chung, Vincent M. and Luevanos, Eloise and Eliasof, Scott and Davis, Mark E. and Yen, Yun (2016) Pilot trial of CRLX101 in patients (pts) with advanced, chemotherapy-refractory gastroesophageal cancer (GEC). Journal of Clinical Oncology, 34 (4). Art. No. 44. ISSN 1527-7755.

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Background: Camptothecin (CPT) derivatives such as irinotecan have activity in 2nd-line therapy in advanced GEC with reported response rates of 0-15%. CRLX101 is an investigational nanoparticle-drug conjugate (NDC) with a CPT payload. Preclinical evidence indicates preferential uptake in tumors, and animal GEC xenograft models demonstrate superiority of CRLX101 over irinotecan. A pilot trial was conducted at recommended phase 2 dosing (RP2D) to assess preferential uptake of CRLX101 in tumor vs. adjacent normal tissue in endoscopically accessible tumors in patients with chemotherapy-refractory GEC. Data demonstrating preferential tumor uptake of CRLX101 has been presented separately and here we report on the clinical outcomes of patients enrolled. Methods: All pts initiated CRLX101 dosed intravenously at RP2D (15 mg/m2) on days 1 and 15 of a 28-day cycle until disease progression or intolerant toxicity. While detection of preferential CRLX101 tumor uptake was the primary endpoint, with 10 pts enrolled a secondary analysis could be performed with the study having 90% power to detect ≥ 1 responder if the true response rate is ≥ 21%. Responses were assessed using RECIST 1.1. Results: Between Dec. 2012 and Dec. 2014, 10 patients with chemotherapy-refractory (median 2 prior lines of therapy, range 1-4) GEC and adenocarcinoma histology were enrolled and evaluable for response and toxicity. The median time-to-progression was 1.9 mo (range 0.6-8.7 mo). Best response was seen in 1 pt with stable disease (SD) for 8 cycles. Only ≥ grade 3 toxicities related to CRLX101 occurred in a single patient with grade 3 anemia and chest pain who was able to resume therapy without any further toxicity after CRLX101 was reduced to 12 mg/m2. Conclusions: CRLX101 demonstrated minimal activity with SD as best response in this heavily pretreated population. Future efforts with CRLX101 in advanced GEC should focus on combination strategies. Its favorable toxicity profile and evidence of preferential tumor uptake support further clinical research of combining CRLX101 with other targeted therapies such as anti-angiogenesis (ramucirumab) and/or immune checkpoint inhibitors. Clinical trial information: NCT01612546 Clinical trial information: NCT01612546.

Item Type:Article
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Davis, Mark E.0000-0001-8294-1477
Yen, Yun0000-0003-0815-412X
Additional Information:© 2016 American Society of Clinical Oncology.
Issue or Number:4
Record Number:CaltechAUTHORS:20160707-082118111
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:68878
Deposited By: Tony Diaz
Deposited On:07 Jul 2016 19:17
Last Modified:20 Nov 2019 20:18

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