Related Experiment Video

Updated: Feb 2, 2026

Vessel-sparing Excision and Primary Anastomosis
08:09

Vessel-sparing Excision and Primary Anastomosis

Published on: January 7, 2019

12.1K

A Phase I/Ib Trial of the VEGFR-Sparing Multikinase RET Inhibitor RXDX-105

Alexander Drilon1, Siqing Fu2, Manish R Patel3

  • 1Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York. drilona@mskcc.org.

Cancer Discovery
|November 30, 2018
PubMed

Insights

The multikinase RET inhibitor RXDX-105 showed limited efficacy in non-small cell lung cancers (NSCLC) with KIF5B-RET fusions. Novel strategies are required to target these specific RET fusion-positive NSCLCs.

Area of Science:

  • Oncology
  • Molecular Biology
  • Clinical Trials

Background:

  • RET fusions are key drivers in various cancers, including non-small cell lung cancer (NSCLC).
  • Targeting oncogenic RET fusions with specific inhibitors is a therapeutic strategy.

Purpose of the Study:

  • To evaluate the safety and antitumor activity of the multikinase RET inhibitor RXDX-105.
  • To determine the efficacy of RXDX-105 in patients with RET fusion-positive NSCLC, stratified by fusion partner.

Main Methods:

  • A phase I/Ib clinical trial was conducted to assess RXDX-105 safety and efficacy.
  • Objective response rates (ORR) were analyzed in RET inhibitor-naïve patients with RET fusion-positive NSCLCs, with a focus on different fusion partners.

Main Results:

  • A recommended phase II dose of 275 mg daily was established.
  • The overall ORR in RET fusion-positive NSCLC was 19%, but responses varied significantly by fusion partner.
  • RXDX-105 showed 0% ORR in patients with KIF5B-RET fusions, the most common type, but 67% ORR in those with non-KIF5B-RET fusions.

Conclusions:

  • RXDX-105 demonstrates differential efficacy based on RET fusion partners in NSCLC.
  • Current RET inhibition is ineffective against KIF5B-RET fusions, necessitating new therapeutic approaches.
  • Further research into the underlying biology of differential responses is crucial for advancing treatment.

More Related Videos

Nerve-sparing Mid-urethral Obstruction NeMO in Female Small Rodents07:42

Nerve-sparing Mid-urethral Obstruction NeMO in Female Small Rodents

Published on: April 25, 2017

10.0K
Retzius-Sparing Robot-Assisted Radical Prostatectomy12:10

Retzius-Sparing Robot-Assisted Radical Prostatectomy

Published on: May 19, 2022

9.3K

Related Concept Videos

Spare Receptors01:30

Spare Receptors

Some receptors remain unoccupied even when an agonist produces a maximal response. Such empty ones are called spare receptors. In presence of spare receptors the maximum effect of an agonist drug is achieved with fewer than 100% of the receptors being occupied. To determine the presence of spare receptors, scientists often compare the concentration of the drug needed to produce 50% of the maximum effect (EC50) with the concentration of the drug needed to occupy 50% of the receptors (Kd). If the...
4.6K
Drugs for Treatment of Diarrhea-Predominant IBS01:17

Drugs for Treatment of Diarrhea-Predominant IBS

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a subtype of IBS characterized primarily by frequent, loose, or watery stools, abdominal pain, and abdominal discomfort. Therapeutic approaches to managing IBS-D include dietary changes, stress management techniques, and pharmaceutical interventions.
Two specific drugs used in the treatment are alosetron (Lotronex) and eluxadoline (Viberzi). Alosetron, a 5-HT3 antagonist, works by slowing the movement of stools in the gut, reducing bowel...
716
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.0K
Drugs for Treatment of Constipation-Predominant IBS01:21

Drugs for Treatment of Constipation-Predominant IBS

Pharmacological therapies for IBS-C are designed to alleviate abdominal discomfort and enhance bowel function. In patients with IBS-C, fiber supplements may help soften stools and decrease straining, but may also lead to increased gas production and bloating. Osmotic laxatives like milk of magnesia are frequently used to soften stools and increase stool frequency in IBS-C patients. In addition, two drugs approved for use in severe IBS-C adult cases are linaclotide (Linzess) and lubiprostone...
834
Clinical Trials: Overview01:11

Clinical Trials: Overview

Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...
4.9K
Trial and Error and Algorithm01:12

Trial and Error and Algorithm

A problem-solving strategy is a plan of action used to find a solution. Different strategies have distinct action plans. Trial and error involves trying different solutions until one works. For instance, to fix a broken printer, you might check ink levels, ensure the paper tray isn't jammed, and verify the printer's connection to your laptop. This method can be time-consuming but is commonly used. Thomas Edison, for example, used trial and error to find a suitable filament for the light...
411