Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Developmental therapeutics

3068 - A Phase 1b study of RXDX-105, a VEGFR-sparing potent RET inhibitor, in RETi-naïve patients with RET fusion-positive NSCLC

Date

10 Sep 2017

Session

Developmental therapeutics

Presenters

Lyudmila Bazhenova

Citation

Annals of Oncology (2017) 28 (suppl_5): v605-v649. 10.1093/annonc/mdx440

Authors

A.E. Drilon1, S. Liu2, R. Doebele3, C. Rodriguez4, M. Fakih5, K.L. Reckamp6, L.1. Bazhenova7, B.C. Cho8, E. Kowack9, J. Oliver10, P. Multani10, M. Ahn11

Author affiliations

  • 1 Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 2 Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, 20007 - Washington DC/US
  • 3 Medical Oncology, University of Colorado, 80045 - Aurora/US
  • 4 Seattle Cancer Care Alliance, University of Washington, 98109 - Seattle/US
  • 5 Medical Oncology, City of Hope, 91010 - Duarte/US
  • 6 Medical Oncology And Therapeutics Research, City of Hope, 91010 - Duarte/US
  • 7 Moores Cancer Center, University of California, 92093 - San Diego/US
  • 8 Division Of Medical Oncology, Department Of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Yonsei/KR
  • 9 Program Management, Ignyta, Inc., 92121 - San Diego/US
  • 10 Clinical Development, Ignyta, Inc., 92121 - San Diego/US
  • 11 Division Of Hematology-oncology, Department Of Medicine, Samsung Medical Center, 82 - Seoul/KR
More

Resources

Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

Abstract 3068

Background

RXDX-105 is a VEGFR-sparing potent RET inhibitor (RETi) with IC50 of 0.3 nM, 0.3-0.8 nM, and 5-15 nM against wt RET, RET fusions, and RET mutations, respectively. RXDX-105 has demonstrated potent antitumor activity in PDX models harboring RET fusions, which occur predominantly in NSCLC (1-2% of adenocarcinomas). More than half of these involve the KIF5B gene as the fusion partner, and pooled efficacy experience with other RET-active agents suggests a lower response rate in this pt population.

Methods

Pts with advanced solid tumors were enrolled in a Phase 1/1b dose escalation study followed by dose expansion at the RP2D. RXDX-105 was given orally at doses ranging from 20 - 350 mg QD. Tumor response was assessed every 8 weeks by RECIST v1.1. Adverse events (AEs) were recorded per NCI CTCAE v4.03.

Results

As of 30Jun2017, 144 (55 Ph 1; 89 Ph 1b) pts (73F; 71M) received RXDX-105; 28 pts remain on treatment. Median age was 63 yrs. Based on safety and PK data, the RP2D was determined to be 275 mg, QD, fed. The most common treatment-related AEs were mostly Grades 1 or 2 and reversible with dose modifications. The most common G3 treatment-related AEs (>5%) were rash (10%), hypophosphatemia (8%), elevated ALT (7%) and anemia (7%). As previously reported, one pt experienced Grade 3 rash complicated by fatal alveolar hemorrhage. No other treatment-related Grade ≥4 AEs were observed. Of the 91 pts treated in Ph 1b, 21 pts had NSCLC harboring RET fusions confirmed by NGS, were RETi naïve, and evaluable for efficacy. Of these, 13 harbored the KIF5B-RET fusion. The other 8 pts had a variety of non-KIF5B-RET fusions; 6 of these 8 pts achieved a confirmed PR for an ORR of 75%. Median DOR has not yet been reached. None of the 13 pts with KIF5B-RET fusions had a RECIST response, although 4 had SD lasting ≥ 6 months. Overall, time on treatment ranges from 0.5+ to 14.5+ months.

Conclusions

RXDX-105 has demonstrated antitumor activity across multiple fusion partners in RET-positive NSCLC pts with a manageable safety profile. However, responses were not observed in pts whose tumors harbored a KIF5B-RET fusion, consistent with previous evidence with other agents, suggesting that this RET fusion may be less susceptible to RET inhibition.

Clinical trial identification

NCT01877811

Legal entity responsible for the study

Ignyta, Inc.

Funding

Ignyta, Inc.

Disclosure

S. Liu: Consultant/Ad board: Genentech, Ignyta, Pfizer, Bristol-Myers Squibb, Lilly, Celgene, Ariad, Boehringer Ingelheim, AstraZeneca. R. Doebele: Advisory Board, Travel reimbursement, and Sponsored Research Agreement from Ignyta. B.C. Cho: Research funding: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST Consulting role: Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Yuhan, Pfizer, Eli Lilly. E. Kowack, J. Oliver, P. Multani: Employee of Ignyta, Inc. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.