dm+d

Unassigned

New Medicines

Gavreto RET-altered non-small cell lung cancer (NSCLC) following chemotherapy

Information

Gavreto
New molecular entity
Roche
Blueprint Medicines Corporation

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Launched
Sep 20Launched in the US [8].
Sep 20Approved in US [7].
Jul 20Roche plans to acquire rights to pralsetinib and gain an exclusive license to sell pralsetinib outside of the U.S. and China.[5]
Jun 20Currently pre-registration in EU. Has been filed using the centralised procedure [4].
May 20US FDA accept NDA with a PDUFA 23/11/20 [6].
Jun 19The company is planning to file in 2020 [2].
May 19Breakthrough therapy designation awarded in US for NSCLC that has progressed following platinum-based chemotherapy [1].
Apr 18Orphan drug designation in US awarded [1].

Category

Proto-oncogene protein C RET inhibitor
RET rearrangements have been seen in 1 to 2% of adenocarcinomas, occurring more frequently in the young and in never-smokers [3].
RET-altered non-small cell lung cancer (NSCLC) following chemotherapy
Oral

Further information

Yes
To be confirmed

Trial or other data

Oct 20PIII AcceleRET trial is recruiting and due to complete collection of primary outcome data in Sep 23. This trial is designed to evaluate whether pralsetinib improves outcome when compared to a platinum chemotherapy-based regimen chosen by the Investigator from a list of standard of care treatments, as measured primarily by progression free survival (PFS), for patients with RET fusion-positive metastatic NSCLC who have not previously received systemic anticancer therapy for metastatic disease (NCT04222972; EudraCT2019-002463-10; BLU-667-2303). The randomised, open-label trial intends to enrol 250 participants in the US, Norway, the UK, Finland, Denmark, Czech Republic, Netherlands, Belgium, France, Italy, South Korea, Poland, Spain and Taiwan [9].
Aug 20PI/II Arrow trial is still recruiting, and due to finish collecting primary outcome data in Dec 21. This first-in-human trial is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of pralsetinib , in patients with NSCLC, thyroid cancer and other advanced solid tumours (BLU-667-1101; NCT03037385). The open-label, single-group trial will enrol 527 patients in the US, China, Spain, the UK, Taiwan, the Netherlands, Singapore, South Korea, Italy, Germany, and France. The study consists of two parts, a dose-escalation part (part 1) and an expansion part (part 2). The dose escalation part is complete and the expansion portion has been initiated and is enrolling patients in six cohorts at MTD of 400mg QD. Both parts will enrol patients with advanced NSCLC, advanced thyroid cancer and other advanced solid tumours that have progressed following standard systemic therapy, have not adequately responded to standard systemic therapy, or in patients who are intolerant to or have declined standard therapy [9].
Jul 20Data from PII Arrow trial (NCT03037385) and PIII AcceleRET trial (NCT04222972) are being used in support of licence applications. Interim results from Arrow trial were presented at ASCO 2020. A paper was submitted to NEJM. 1 - Gainor et al. Registrational Dataset from the Phase 1/2 ARROW Trial of Pralsetinib (BLU-667) in Patients with Advanced RETFusion+ Non-Small Cell Lung Cancer (NSCLC). Poster Number 9515. Presented at ASCO 2020, May 29 –June 2, 2020, Virtual Format. [4].
Jun 19Preliminary top line PII data looking at 35 patients with NSCLC show that 90% had "some tumour shrinkage", and 60% of patients were responders to treatment. Tumours that had spread to the brain shrank in seven out of nine patients. NSCLC is only one indication in this trial; other patients have thyroid cancer, pancreatic cancer and bile duct cancer [2].

Evidence based evaluations

GavretoMedullary advanced/metastatic RET mutant (MTC) and RET fusion-positive thyroid cancer

Information

Gavreto
Licence extension / variation
Roche
Blueprint Medicines Corporation

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Launched
Dec 20FDA approves pralsetinib for thyroid cancer under its accelerated approval programme based on data from the PI/II ARROW study. Pralsetinib has breakthrough therapy status in the US for the treatment of RET-mutation-positive medullary thyroid cancer, which needs systemic treatment and for which there are no acceptable alternative treatments. It also has orphan drug status in the US [8].
Dec 20FDA approve pralsetinib for advanced or metastatic RET-mutant and RET fusion-positive thyroid cancer [6].
Jul 20Blueprint Medicines announce submission of NDA to FDA for treatment of advanced RET mutant and RET fusion-positive thyroid cancers [1].

Category

Proto-oncogene protein C RET inhibitor
There are around 3,500 new thyroid cancer cases in the UK every year [3]. MTC accounts for approximately 5-8% of all thyroid cancer. Clinically, MTC is mainly sporadic (70-80%), but hereditary pattern is present in 20-30% of cases, transmitted as an autosomal dominant trait. Somatic RET mutations can be detected in tumour tissue of 40-60% of sporadic MTC patients [4].
Medullary advanced/metastatic RET mutant (MTC) and RET fusion-positive thyroid cancer
Oral

Trial or other data

Aug 20PI/II Arrow trial is still recruiting, and due to finish collecting primary outcome data in Dec 21. This first-in-human trial is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of pralsetinib , in patients with NSCLC, thyroid cancer and other advanced solid tumours (BLU-667-1101; NCT03037385). The open-label, single-group trial will enrol 527 patients in the US, China, Spain, the UK, Taiwan, the Netherlands, Singapore, South Korea, Italy, Germany, and France. The study consists of two parts, a dose-escalation part (part 1) and an expansion part (part 2). The dose escalation part is complete and the expansion portion has been initiated and is enrolling patients in six cohorts at MTD of 400mg QD. Both parts will enrol patients with advanced NSCLC, advanced thyroid cancer and other advanced solid tumours that have progressed following standard systemic therapy, have not adequately responded to standard systemic therapy, or in patients who are intolerant to or have declined standard therapy [7].
Jul 20Estimated primary completion date of PIII ARROW study (NCT03037385) is Dec 21 [2].