| Title |
First-in-human phase 1/2a trial of CRLX101, a cyclodextrin-containing polymer-camptothecin nanopharmaceutical in patients with advanced solid tumor malignancies
|
|---|---|
| Published in |
Investigational New Drugs, February 2013
|
| DOI | 10.1007/s10637-012-9921-8 |
| Pubmed ID | |
| Authors |
Glen J. Weiss, Joseph Chao, Jeffrey D. Neidhart, Ramesh K. Ramanathan, Dawn Bassett, James A. Neidhart, Chung Hang J. Choi, Warren Chow, Vincent Chung, Stephen J. Forman, Edward Garmey, Jungyeon Hwang, D. Lynn Kalinoski, Marianna Koczywas, Jeffrey Longmate, Roger J. Melton, Robert Morgan, Jamie Oliver, Joanna J. Peterkin, John L. Ryan, Thomas Schluep, Timothy W. Synold, Przemyslaw Twardowski, Mark E. Davis, Yun Yen |
| Abstract |
Patients with advanced solid malignancies were enrolled to an open-label, single-arm, dose-escalation study, in which CRLX101 was administered intravenously over 60 min among two dosing schedules, initially weekly at 6, 12, and 18 mg/m(2) and later bi-weekly at 12, 15, and 18 mg/m(2). The maximum tolerated dose (MTD) was determined at 15 mg/m(2) bi-weekly, and an expansion phase 2a study was completed. Patient samples were obtained for pharmacokinetic (PK) and pharmacodynamic (PD) assessments. Response was evaluated per RECIST criteria v1.0 every 8 weeks. Sixty-two patients (31 male; median age 63 years, range 39-79) received treatment. Bi-weekly dosing was generally well tolerated with myelosuppression being the dose-limiting toxicity. Among all phase 1/2a patients receiving the MTD (n = 44), most common grade 3/4 adverse events were neutropenia and fatigue. Evidence of systemic plasma exposure to both the polymer-conjugated and unconjugated CPT was observed in all treated patients. Mean elimination unconjugated CPT Tmax values ranged from 17.7 to 24.5 h, and maximum plasma concentrations and areas under the curve were generally proportional to dose for both polymer-conjugated and unconjugated CPT. Best overall response was stable disease in 28 patients (64 %) treated at the MTD and 16 (73 %) of a subset of NSCLC patients. Median progression-free survival (PFS) for patients treated at the MTD was 3.7 months and for the subset of NSCLC patients was 4.4 months. These combined phase 1/2a data demonstrate encouraging safety, pharmacokinetic, and efficacy results. Multinational phase 2 clinical development of CRLX101 across multiple tumor types is ongoing. |
Mendeley readers
The data shown below were compiled from readership statistics for 138 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 1% |
| United Kingdom | 1 | <1% |
| Netherlands | 1 | <1% |
| Unknown | 134 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 25 | 18% |
| Student > Master | 18 | 13% |
| Researcher | 17 | 12% |
| Student > Bachelor | 14 | 10% |
| Student > Doctoral Student | 9 | 7% |
| Other | 21 | 15% |
| Unknown | 34 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 20 | 14% |
| Chemistry | 16 | 12% |
| Pharmacology, Toxicology and Pharmaceutical Science | 14 | 10% |
| Agricultural and Biological Sciences | 12 | 9% |
| Biochemistry, Genetics and Molecular Biology | 11 | 8% |
| Other | 28 | 20% |
| Unknown | 37 | 27% |
Attention Score in Context
This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 October 2022.
All research outputs
#3,406,572
of 23,506,079 outputs
Outputs from Investigational New Drugs
#96
of 1,197 outputs
Outputs of similar age
#36,905
of 289,221 outputs
Outputs of similar age from Investigational New Drugs
#2
of 8 outputs
Altmetric has tracked 23,506,079 research outputs across all sources so far. Compared to these this one has done well and is in the 84th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,197 research outputs from this source. They receive a mean Attention Score of 4.8. This one has done well, scoring higher than 89% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 289,221 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 86% of its contemporaries.
We're also able to compare this research output to 8 others from the same source and published within six weeks on either side of this one. This one has scored higher than 6 of them.