A Phase I/Ib Trial of the VEGFR-Sparing Multikinase RET Inhibitor RXDX-105
fusions are oncogenic drivers of various tumors, including non-small cell lung cancers (NSCLC). The safety and antitumor activity of the multikinase RET inhibitor RXDX-105 were explored in a phase I/Ib trial. A recommended phase II dose of 275 mg fed daily was identified. The most common treatment-r...
Gespeichert in:
Veröffentlicht in: | Cancer discovery 2019-03, Vol.9 (3), p.384-395 |
---|---|
Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | fusions are oncogenic drivers of various tumors, including non-small cell lung cancers (NSCLC). The safety and antitumor activity of the multikinase RET inhibitor RXDX-105 were explored in a phase I/Ib trial. A recommended phase II dose of 275 mg fed daily was identified. The most common treatment-related adverse events were fatigue (25%), diarrhea (24%), hypophosphatemia (18%), maculopapular rash (18%), and nonmaculopapular rash (17%). In the phase Ib cohort of RET inhibitor-naïve patients with
fusion-positive NSCLCs, the objective response rate (ORR) was 19% (95% CI, 8%-38%,
= 6/31). Interestingly, the ORR varied significantly by the gene fusion partner (
< 0.001, Fisher exact test): 0% (95% CI, 0%-17%,
= 0/20) with
(the most common upstream partner for
fusion-positive NSCLC), and 67% (95% CI, 30%-93%,
= 6/9) with non-
partners. The median duration of response in all
fusion-positive NSCLCs was not reached (range, 5 to 18+ months). SIGNIFICANCE: Although
is the most common
fusion in NSCLCs, RET inhibition with RXDX-105 resulted in responses only in non-
-containing cancers. Novel approaches to targeting
-containing tumors are needed, along with a deeper understanding of the biology that underlies the differential responses observed.
. |
---|---|
ISSN: | 2159-8274 2159-8290 |
DOI: | 10.1158/2159-8290.CD-18-0839 |