Entrectinib

Unassigned

New Medicines

Rozlytrek · 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

Rozlytrek
New molecular entity
Roche
Roche

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Approved (Licensed)
Yes
Aug 19 · Approved in the US for treatment of adult and pediatric patients 12 years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy [12].
Jun 19 · Japanese Ministry of Health, Labour and Welfare (MHLW) approved entrectinib for treatment of pts with NTRK fusion-positive, advanced recurrent solid tumours. In Japan, it has been granted Sakigake designation and orphan drug designation by the MHLW (which is similar to Breakthrough status in the USA). [10,11]
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
February 2020

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

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

Information

Rozlytrek
Licence extension / variation
Roche
Roche

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Approved (Licensed)
Aug 19 · Approved in the US for treatment of adults with ROS1-positive, metastatic NSCLC [7].
Feb 19 · Filed in EU [6].
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
February 2020

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