dm+d

Unassigned

New Medicines

VitrakviSolid tumours with NTRK1, NTRK2 or NTRK3 gene fusion

Information

Vitrakvi
New molecular entity
Bayer
Bayer

Development and Regulatory status

Launched
Launched
Launched
October 2019
Yes
Feb 21Viktravi oral capsules available in the UK. Price for 56 capsules = £14,000 (100mg) and £3,500 (25mg) [17].
Oct 19Available in the UK. Price 1 x 100ml bottle 20mg/ml oral solution = £5,000 [16].
Sep 19Approved in EU [15].
Jul 19Recommended for EU conditional approval by CHMP - the full indication is "for the treatment of adult and paediatric patients with solid tumours that display 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 no satisfactory treatment options (see sections 4.4 and 5.1).” It is proposed that the medicine be initiated by physicians experienced in the administration of anticancer therapies [14].
Feb 19Bayer announces it will now be solely responsible for the global development and commercialisation of Vitrakvi [13].
Nov 18In the US, larotrectinib will be priced at $32,800 per month (wholesale) although access programs will be available [12].
Nov 18Approved in the US [11].
Aug 18MAA for larotrectinib has been submitted to the EMA, to treat adult and pediatric patients with locally advanced or metastatic solid tumors with NTRK gene fusion [10].
May 18Granted priority review in US [9].
Mar 18Filed in the US for treatment of adults & pediatric patients with locally advanced or metastatic solid tumors harboring a neurotrophic tyrosine receptor kinase (NTRK) gene fusion. EU filing planned for 2018 [8].
Nov 17Loxo announces partnership with Bayer to develop and commercialise larotrectinib, and a follow-up compound LOXO-195. Loxo will lead all development and US regulatory activity, and Bayer will lead regulatory activity and commercialisation elsewhere; the companies will co-promote the products in the US [6]. The companies have confirmed that first filing in the US is planned late 2017 or early 2018, and EU filing is planned during 2018 [7].
Oct 17Following the assessment from the Independent Review Committee, Loxo Oncology expects to submit a New Drug Application (NDA) to the FDA in late 2017 or early 2018, and a Marketing Authorisation Application (MAA) to the EMA in 2018 [5].
May 17FDA Orphan Drug Designation granted to larotrectinib for treatment of solid tumours with NTRK-fusion proteins [3].
Dec 16Loxo Oncology intends to file in the US in late 2017 or early 2018 and in the EU in 2018, for the treatment of unresectable or metastatic solid tumours with NTRK-fusion proteins in adult and paediatric patients who require systemic therapy and who have either progressed following prior treatment or who have no acceptable alternative treatments [2].
Jul 16FDA grants breakthrough therapy designation to larotrectinib for treatment of metastatic solid tumours with NTRK fusion proteins in adult and paediatric patients [2].

Category

Pan-Trk inhibitor with highly selective activity against the Trk kinase family. The company believes that its selectivity will ensure maximal efficacy, while sparing structurally similar targets such as ALK, JAK and VEGF, so reducing toxicity.
The Trk receptor family comprises three transmembrane proteins referred to as Trk A, B and C (TrkA, TrkB and TrkC) receptors, and are encoded by the NTRK1, NTRK2 and NTRK3 genes, respectively. Tumours with gene fusions involving NTRK genes include colorectal, papillary thyroid carcinoma, human secretory breast carcinoma and glioblastoma [1].
Solid tumours with NTRK1, NTRK2 or NTRK3 gene fusion
Oral

Further information

Yes

Trial or other data

Jun 21Company will present expanded data results for pts with TRK fusion cancer of multiple tumour types at the American Society of Clinical Oncology Annual meeting on 4/6/21- 8/6/21 (n=206 adults and paediatric pts). ORR was found to be 75% with 22% complete responses. For pts with brain metastases, the ORR was 73%. The median duration of response was 49.3 months at a median follow-up of 22.3 months. For pts with lung cancer (n=50), ORR was 73% with remarkable durability at 34 months and with a PFS of 35 months. [18]
Oct 17The Independent Review Committee assessing the larotrectinib dataset (intention to treat, n=55) has completed its review and has broadly agreed with the investigator assessed response. Overall Response Rate (ORR) was 75% (vs. 80% in the investigator assessment) with complete response in 13% (vs. 16%) and partial response in 62% (vs. 64%). Recruitment to the trial programme continues, with activity and safety consistent with data so far reported [5].
Jun 17Loxo announces data from three trials, a PI study in adults, a PII study called Navigate, and a PI/II pediatric trial called Scout. The results were based on the intention-to-treat principle, using the first 55 TRK fusion patients enrolled to the three trials, regardless of their prior therapy or tumor-tissue diagnostic method. In all, 44 adults and 12 younger patients were enrolled, with tumors identified by 14 different lab tests. The TRK fusion patients carried a host of primary diagnoses, including appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, gastrointestinal stromal tumor, infantile fibrosarcoma, lung cancer and more. The confirmed overall response rate was 76% in 50 patients, with these rates generally consistent across tumor types, TRK gene fusions, and various diagnostic tests. In the pediatric setting, larotrectinib also showed promising activity in the presurgical management of patients with infantile fibrosarcoma, with three patients treated to best response. Seven (13%) of the study patients had their doses reduced because of side effects, but no patients stopped taking larotrectinib after suffering side effects. All patients whose doses were lowered experienced tumor regression, which then continued on the reduced dose. Nearly all of the dose reductions were due to infrequent neurocognitive adverse events. Loxo added that six patients responded to larotrectinib but later progressed. The company is gathering other evidence for larotrectinib´s application for FDA approval. A central, independent radiology review will be performed in the second half of 2017, and Loxo plans to announce that data before the end of the year. A separate assessment by independent radiologists, not yet conducted, will also be required to support its regulatory filing [4].
Oct 15Loxo Oncology initiates the PII NAVIGATE basket trial of larotrectinib in solid tumour patients with tropomysin receptor kinase (TRK) fusions (LOXO-TRK-15002; NCT02576431). The single arm trial intends to recruit approximately 150 patients with locally advanced or metastatic non-small cell lung cancer, thyroid cancer, sarcoma, colorectal cancer, salivary gland cancer, biliary cancer, primary central nervous system tumours and all other solid tumour histologies in 8 cohorts. The primary endpoint for the trial is overall response rate as measured by Response Evaluation criteria in Solid Tumours (RECIST). Recruitment is underway in the US, Denmark, South Korea, Singapore, Spain and Ireland. A dose of 100mg twice-daily for a phase II study has been selected based on phase Ia part data [2].

Evidence based evaluations