dm+d

38882711000001106

New Medicines

RozlytrekAdvanced 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

Launched
Launched
Approved (Licensed)
August 2020
Yes
Aug 20Available in UK. 100mg yellow cap marked ENT 100, 30=£860; 200mg orange cap marked ENT 200, 90=£5,160 [15].
Aug 20Granted conditional MA in EU for treatment of locally advanced, metastatic solid tumours expressing a NTRK gene fusion in adults and children aged ≥12 years who have no satisfactory treatment options. Patients must not have been treated with a NTRK inhibitor previously [14].
May 20Recommended for EU approval by CHMP - the full indication is "as monotherapy ... for the treatment of adult and paediatric patients 12 years of age and older, with solid tumours expressing a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, who have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, and who have not received a prior NTRK inhibitor, who have no satisfactory treatment options (see sections 4.4 and 5.1); and, as monotherapy ... for the treatment of adult patients with ROS1-positive, advanced non-small cell lung cancer (NSCLC) not previously treated with ROS1 inhibitors." It is proposed that the medicine be prescribed by physicians experienced in the use of anticancer therapies. [13]
Aug 19Approved 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 19Japanese 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 19Filed in EU [9].
Feb 19Granted priority review in US [8]
Apr 18EU & US filings for NSCLC ROS1-positive and NTRK1 pantumour planned for 2019 [7].
Oct 17Awarded 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 17Ignyta 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 17US FDA grants orphan drug designation to entrectinib for treatment of NTRK fusion-positive solid tumours [2].
May 17Granted 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

Trial or other data

Dec 18PII STARTRK-2 study is still recruiting pts. Collection of primary outcome data is now due to complete Oct 19 [6].
Oct 17PII STARTRK-2 study is still recruiting pts. Collection of primary outcome data (objective response rate) is due to complete Oct 17 [6].
Sep 15Ignyta 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

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

Information

Rozlytrek
New molecular entity
Roche
Roche

Development and Regulatory status

Launched
Launched
Approved (Licensed)
August 2020
Oct 21Filings using B-FAST now expected 2022 [12].
Sep 20Roche plans to file data from the Rozlytrek cohort (D) of ROS1-positive patients in the B-FAST study in 2021. This study is designed to evaluate the safety and efficacy of targeted therapies or immunotherapy as single agents or in combination in participants with unresectable, advanced or metastatic NSCLC determined to harbor oncogenic somatic mutations or positive by tumor mutational burden (TMB) assay as identified by two blood-based next-generation sequencing (NGS) circulating tumor DNA (ctDNA) assays [11].
Aug 20Available in UK. 100mg yellow cap marked ENT 100, 30=£860; 200mg orange cap marked ENT 200, 90=£5,160 [10].
Aug 20Approved in EU for the treatment of adults with ROS-1 positive, advanced NSCLC who have not been previously treated with a ROS1 inhibitor [9].
May 20Recommended for EU approval by CHMP - the full indication is "as monotherapy ... for the treatment of adult and paediatric patients 12 years of age and older, with solid tumours expressing a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, who have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, and who have not received a prior NTRK inhibitor, who have no satisfactory treatment options (see sections 4.4 and 5.1); and, as monotherapy ... for the treatment of adult patients with ROS1-positive, advanced non-small cell lung cancer (NSCLC) not previously treated with ROS1 inhibitors." It is proposed that the medicine be prescribed by physicians experienced in the use of anticancer therapies. [13]
Aug 19Approved in the US for treatment of adults with ROS1-positive, metastatic NSCLC [7].
Feb 19Filed in EU [6].
Feb 19Filed in US with priority review status. A decision is expected by 18/8/19 [5].
Sep 17Ignyta 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

Trial or other data

Dec 18PII STARTRK-2 study is still recruiting pts. Collection of primary outcome data is now due to complete Oct 19 [3].
Oct 17PII STARTRK-2 study is still recruiting pts. Collection of primary outcome data (objective response rate) is due to complete Oct 17 [3].
Sep 15Ignyta 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