marked.bio

ALK TKI (2nd generation) · small molecule

ceritinib

3 active trials across 2 of our biomarkers, targeting ALK. 3 active approvals for a biomarker on marked.bio.

Also known as LDK378, Zykadia.

Counts only trials that select patients by one of the biomarkers on marked.bio, not every trial of this drug.

Approvals and pivotal results

Biomarker-selected approvals in the United States and the European Union, with the pivotal trial's results and side effects where we have them. Results from different trials are not directly comparable.

TherapyBiomarkerTumourUnited StatesEuropean Union
ceritinib
FDA, 2014
metastatic, ALK-positive AA 29/04/2014 (after crizotinib), converted to regular approval 26/05/2017 with first-line use; current label: ALK-positive metastatic NSCLC. Source
EU (EMA), 2015
ALK-positive advanced NSCLC previously treated with crizotinib Conditional MA 06/05/2015, switched to full MA 26/07/2017. First-line indication added 23/06/2017 (II/0012), now its own row. Source
EU (EMA), 2017
first line, ALK-positive advanced NSCLC II/0012 added first-line use (EC decision 23/06/2017). Current SmPC section 4.1 lists both first-line and post-crizotinib ALK-positive advanced NSCLC. Source
Zykadia 		ALK fusion NSCLC Approved 2014 Approved 2015

In the US approval report

ASCEND-4 vs platinum + pemetrexed chemotherapy, 189 vs 187 patients
PFS 16.6 months vs 8.1 months, HR 0.55 (0.42-0.73)Response 73% vs 27%OS HR no significant difference at interim analysis

Serious side effects 38%Stopped for side effects 12%Fatal 4 patients

Trial details and side effects
Patients
first-line ALK-positive NSCLC (NCT01828099)
Most common side effects
diarrhoea 85%, nausea 69%, vomiting 67%, fatigue 45%, abdominal pain 40%, decreased appetite 34% (189 patients)
Notes
US label rev. 10/2021.
Source
US approval report

In the EU product information

ASCEND-5 vs pemetrexed or docetaxel, 115 vs 116 patients
PFS 5.4 months vs 1.6 months, HR 0.49 (0.36-0.67)Response 39% vs 7%

Trial details and side effects
Patients
ALK-positive NSCLC after crizotinib and chemotherapy (NCT01828112)
Notes
EU SmPC section 5.1: the EU indication after crizotinib rests on the randomised ASCEND-5 trial.
Source
EU product information

Biomarkers

BiomarkerActive trialsAll trialsFurthest active phase
ALK fusion 3 25 Phase 4
ROS1 fusion 0 5 –

Sponsors

Industry sponsors leading active biomarker-selected trials of ceritinib.

  1. Novartis 2

Trials

3 of 27 trials shown

  1. Roll-over Study to Allow Access to Certinib (LDK378) for Patients Who Are on Ceritinib Treatment in a Novartis-sponsored Study

    Active, not recruiting Phase 4 Novartis Started 2015Primary completion 2027-06 NCT02584933

    ceritinib FDA EU

    An Open-label, Multi-center, Phase IV Roll-over Study in Patients With ALK Positive Malignancies Who Have Completed a Novartis-sponsored Ceritinib (LDK378) Study and Are Jud…

    ALK fusionALK Positive Malignancies

  2. Ceritinib and Everolimus in Treating Patients With Locally Advanced or Metastatic Solid Tumors or Stage IIIB-IV Non-small Cell Lung Cancer

    Active, not recruiting Phase 1 M.D. Anderson Cancer Center Started 2016Primary completion 2026-12 NCT02321501

    ceritinib FDA EUeverolimus

    For dose expansion cohort: patients with stage IIIB or IV ALK + NSCLC who have failed at least one line of therapy and are progressing on an ALK inhibito…

    ALK fusionALK Positive, Locally Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, ROS1 Gene Rearrangement

  3. Study of Safety and Efficacy of Ceritinib in Combination With Nivolumab in Patients With ALK-positive Non-small Cell Lung Cancer

    Active, not recruiting Phase 1 Novartis Started 2015Primary completion 2027-04 NCT02393625

    ceritinib FDA EUnivolumab

    Histologically or cytologically confirmed diagnosis of NSCLC that carries an ALK rearrangement

    ALK fusionALK-positive NSCLC