Entrectinib

Unassigned

New Medicines

Advanced solid tumours, NTRK fusion-positive, ROS1-positive or ALK-positive - in patients who have either progressed following prior therapies or who have no acceptable standard therapy.

Information

New molecular entity
Roche
Roche

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Pre-registration (Filed)
Yes

Feb 19: Filed in EU [9].


Feb 19 : Granted priority review in US [8]


Apr 18: EU & US filings for NSCLC ROS1-positive and NTRK1 pantumour planned for 2019 [7].


Oct 17: Awarded Priority Medicines (PRIME) designation in the EU for treatment of NTRK fusion-positive, locally advanced or metastatic solid tumours in patients who have either progressed following prior therapies or who have no acceptable standard therapy [3].


Sep 17: Ignyta announces that the US FDA has confirmed that the NDA submission for ROS1-positive non-small cell lung cancer (NSCLC) will be based on the phase I ALKA and STARTRK-1 trials and the phase II STARTRK-2 trial [2].


Jul 17: US FDA grants orphan drug designation to entrectinib for treatment of NTRK fusion-positive solid tumours [2].


May 17: Granted breakthrough therapy designation by the US FDA for treatment of NTRK fusion-positive, locally advanced or metastatic solid tumours in adult and paediatric patients who have either progressed following prior therapies or who have no acceptable standard therapies [2].

Category

Selective tyrosine kinase inhibitor of the Trk family of tyrosine kinase receptors (TrkA/B/C), ROS1 and ALK (anaplastic lymphoma kinase) proteins
The neurotrophic tyrosine receptor kinases are a family of genes (NTRK1, NTRK2, and NTRK3) that encode the proteins TrkA, TrkB, and TrkC, respectively [4]. They have been detected in a wide range of cancers [4]. The low prevalence of NTRK fusions in individual tumor types has necessitated the use of novel clinical trial designs, such as basket trials [5]. Rearrangements of the ROS1 gene occur in 1–2 % of non-small cell lung cancers (NSCLCs) [1].
Advanced solid tumours, NTRK fusion-positive, ROS1-positive or ALK-positive - in patients who have either progressed following prior therapies or who have no acceptable standard therapy.
Oral

Further information

Yes
To be confirmed

Trial or other data

Dec 18: PII STARTRK-2 study is still recruiting pts. Collection of primary outcome data is now due to complete Oct 19 [6].


Oct 17: PII STARTRK-2 study is still recruiting pts. Collection of primary outcome data (objective response rate) is due to complete Oct 17 [6].


Sep 15: Ignyta initiated the global, open-label, pivotal, PII STARTRK-2 (Studies of Tumor Alterations Responsive to Targeting Receptor Kinases-2) trial to evaluate the safety and efficacy of entrectinib for the treatment of solid tumours including colorectal cancer and NSCLC (RXDX-101-02; NCT02568267). The trial utilises basket design enabling screening of patient tumour samples for the relevant targets. The trial intends to enrol patients in the US, the EU, and Asia [2].


Evidence based evaluations

Locally advanced or metastatic, ROS-1 fusion-positive non-small cell lung cancer (NSCLC)

Information

Licence extension / variation
Roche
Roche

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Pre-registration (Filed)

Feb 19: Filed in EU [9].


Feb 19: Filed in US with priority review status. A decision is expected by 18/8/19 [5].


Sep 17: Ignyta announces that the US FDA has confirmed that the NDA submission for ROS1-positive non-small cell lung cancer (NSCLC) will be based on the phase I ALKA and STARTRK-1 trials and the phase II STARTRK-2 trial [4].


Category

Selective tyrosine kinase inhibitor of the Trk family of tyrosine kinase receptors (TrkA/B/C), ROS1 and ALK (anaplastic lymphoma kinase) proteins
In 2015, approximately 31,700 people were diagnosed with NSCLC in England, of whom 53% had stage IV disease. It is estimated that ROS1 rearrangements occur in around 1% of patients with NSCLC [1]
Locally advanced or metastatic, ROS-1 fusion-positive non-small cell lung cancer (NSCLC)
Oral

Further information

Yes
To be confirmed

Trial or other data

Dec 18: PII STARTRK-2 study is still recruiting pts. Collection of primary outcome data is now due to complete Oct 19 [3].


Oct 17: PII STARTRK-2 study is still recruiting pts. Collection of primary outcome data (objective response rate) is due to complete Oct 17 [3].


Sep 15: Ignyta initiated the global, open-label, pivotal, PII STARTRK-2 (Studies of Tumor Alterations Responsive to Targeting Receptor Kinases-2) trial to evaluate the safety and efficacy of entrectinib for the treatment of solid tumours including colorectal cancer and NSCLC (RXDX-101-02; NCT02568267). The trial utilises basket design enabling screening of patient tumour samples for the relevant targets. The trial intends to enrol patients in the US, the EU, and Asia [2,3].


Evidence based evaluations