Selpercatinib

Unassigned

New Medicines

Revetmo · Medullary thyroid cancer - advanced/metastatic RET-mutant - first line or after prior treatment with cabozantinib or vandetanib in adults and paediatric patients aged 12 and over

Information

Revetmo
New molecular entity
Eli Lilly
Eli Lilly

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Launched
Yes
Jun 20 · Has orphan drug status in US for treatment of RET-fusion-positive NSCLC [13].
May 20 · Launched in the US with a list price of about $20,600 for a 30-day supply [12].
May 20 · Approved in US. [10]
May 20 · Approved in US [10]
Feb 20 · Currently pre-registration in EU. Has been filed using the EU centralised procedure [8].
Jan 20 · FDA priority review awarded, so expect Q3 2020 decision on licensing approval [6].
Aug 19 · Has breakthrough therapy status in US [4].

Category

A highly selective, adenosine triphosphate -competitive small molecule inhibitor of the rearranged during transfection (RET) receptor tyrosine kinase (RTK).
There are around 3,500 new thyroid cancer cases in the UK every year [1]. 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 [2].
Medullary thyroid cancer - advanced/metastatic RET-mutant - first line or after prior treatment with cabozantinib or vandetanib in adults and paediatric patients aged 12 and over
Oral

Further information

Yes
To be confirmed

Trial or other data

May 20 · Approval in the US is based on results of the LIBRETTO-001 trial (NCT03157128) in which patients received 160mg selpercatinib orally twice daily until disease progression or unacceptable toxicity. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR). The study enrolled 143 patients aged 12 years of age and older with advanced or metastatic RET-mutant MTC who had been previously treated with cabozantinib, vandetanib or both (types of chemotherapy), and patients with advanced or metastatic RET-mutant MTC who had not received prior treatment with cabozantinib or vandetanib. The ORR for the 55 previously treated patients was 69%. For 76% of patients who had a response to the treatment, their response lasted at least six months. Efficacy was also evaluated in 88 patients who had not been previously treated with an approved therapy for MTC. The ORR for these patients was 73%. For 61% of patients who had a response to the treatment, their response lasted at least 6 months [11].
Feb 20 · PIII LIBRETTO-531 (NCT04211337) will recruit patients in countries around the world, including the US, EU & UK. Collection of primary outcome data (Treatment Failure-Free Survival ) is due to complete Feb 23 [9]
Jan 20 · PIII trial LIBRETTO-531 starts, in patients with treatment-naïve RET-mutant MTC. The trial will enrol 400 patients with advanced or metastatic RET-mutant MTC who have received no prior systemic therapy for metastatic disease and compare selpercatinib with cabozantinib or vandetanib as initial treatment [7].
Oct 19 · Lilly reported LIBRETTO-001 data from 76 patients who had not received any kind of cancer treatment and 26 “heavily pretreated” patients in which selpercatinib shrank tumors in 59% of patients in the 1st group and 62% of patients in the 2nd group. Patients were followed up for 6 months [5].
Sep 19 · PI/II LIBRETTO-001 study is recruiting [3].
May 17 · PI/II LIBRETTO-001 study to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of LOXO-292 administered orally to patients with advanced solid tumors, including RET-fusion-positive solid tumors, medullary thyroid cancer (MTC) and other tumors with RET activation starts (NCT03157128). 970 adults and children aged 12 years or older will be recruited from sites including the US, EU & UK. Collection of primary outcome data is due to complete Mar 22 [3].

Evidence based evaluations

Revetmo · Non-small cell lung cancer (NSCLC) - metastatic RET fusion-positive in adults- first line or after prior treatment with platinum-based chemotherapy

Information

Revetmo
New molecular entity
Eli Lilly
Eli Lilly

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Launched
Yes
May 20 · Approved in US. [10]
May 20 · Launched in the US priced at $20,600 for a 30-day supply [12].
Feb 20 · Currently pre-registration in EU. Has been filed using centralised procedure [8].
Jan 20 · FDA priority review awarded, so expect Q3 2020 decision on licensing approval [6].
Sep 19 · Loxo Oncology is now owned by Eli Lilly. US filing planned before the end of 2019 [5].
Aug 19 · Has breakthrough therapy status in US [4].

Category

A highly selective, adenosine triphosphate -competitive small molecule inhibitor of the rearranged during transfection (RET) receptor tyrosine kinase (RTK).
During 2011 there were 43,463 new cases of lung cancer in the UK, an incidence rate of 48.5 per 100,000 persons. Prevalence increased by 10% between 2008 and 2012. Stable incidence and rising prevalence point to improving lung cancer survival rates [1]. EGFR, ALK, and ROS1 are 3 major driver genes that play an important role in lung cancer development and precision management. RET rearrangement is detected in 1% to 2% of cases [2].
Non-small cell lung cancer (NSCLC) - metastatic RET fusion-positive in adults- first line or after prior treatment with platinum-based chemotherapy
Oral

Further information

Yes
To be confirmed

Trial or other data

May 20 · FDA approval was based on results of the LIBRETTO-001 trial. During the trial, patients received 160 mg selpercatinib (Retevmo) orally twice daily until disease progression or unacceptable toxicity. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR). Efficacy for NSCLC was evaluated in 105 adult patients with RET fusion-positive NSCLC who were previously treated with platinum chemotherapy. The ORR for the 105 patients was 64%. For 81% of patients who had a response to the treatment, their response lasted at least six months. Efficacy was also evaluated in 39 patients with RET fusion-positive NSCLC who had never undergone treatment. The ORR for these patients was 84%. For 58% of patients who had a response to the treatment, their response lasted at least 6 months [11].
Feb 20 · PIII LIBRETTO-431 study (NCT04194944) is recruiting in countries around the world including the US, EU & UK. Collection of primary outcome data (progression-free survival) is due to complete Dec 23 [9].
Jan 20 · PIII trial LIBRETTO-431 starts in treatment-naïve RET fusion-positive NSCLC. The trial will enroll 400 patients with advanced or metastatic RET fusion-positive NSCLC who have received no prior systemic therapy for metastatic disease [7].
Sep 19 · New data from PI/II LIBRETTO-001 study reported at the World Conference on Lung Cancer. Selpercatinib showed a 68% objective response rate (ORR) in heavily pretreated RET fusion-positive non-small cell lung cancer (NSCLC). Nine patients (1.7%) stopped treatment as a result of toxicity out of more than 500 across the study [5].
Sep 19 · PI/II LIBRETTO-001 study is recruiting [3].
May 17 · PI/II LIBRETTO-001 study to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of LOXO-292 administered orally to patients with advanced solid tumors, including RET-fusion-positive solid tumors, medullary thyroid cancer (MTC) and other tumors with RET activation starts (NCT03157128). 970 adults and children aged 12 years or older will be recruited from sites including the US, EU & UK. Collection of primary outcome data is due to complete Mar 22 [3].

Evidence based evaluations

Revetmo · Medullary thyroid cancer - advanced/metastatic RET fusion-positive in patients who are radioactive iodine-refractory; adults and paediatrics aged 12 years and over

Information

Revetmo
Licence extension / variation
Eli Lilly
Eli Lilly

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Launched
Yes
May 20 · Launched in the US with a list price of about $20,600 for a 30-day supply [6]
May 20 · Approved in the US [5].
Feb 20 · Currently pre-registration in EU. Has been filed using the EU centralised procedure [7].
Nov 19 · Granted orphan therapy status in the US for the treatment of RET fusion-positive or RET mutant thyroid cancers including poorly differentiated thyroid cancer, undifferentiated or anaplastic thyroid cancer, medullary thyroid cancer, and locally advanced or metastatic follicular or papillary thyroid cancer [4].
Aug 19 · Has breakthrough therapy status in the US [3].

Category

A highly selective, adenosine triphosphate -competitive small molecule inhibitor of the rearranged during transfection (RET) receptor tyrosine kinase (RTK).
There are around 3,500 new thyroid cancer cases in the UK every year [1]. 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 [2].
Medullary thyroid cancer - advanced/metastatic RET fusion-positive in patients who are radioactive iodine-refractory; adults and paediatrics aged 12 years and over
Oral

Further information

Yes
tbc

Trial or other data

May 20 · US approval based on the results of the PI/II LIBRETTO-001 clinical trial (EudraCT2017-000800-59; NCT03157128) in which patients received 160 mg selpercatinib orally twice daily until disease progression or unacceptable toxicity. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR). Efficacy for RET fusion-positive thyroid cancer was evaluated in adults and pediatric patients 12 years of age and older. The study enrolled 19 patients with RET fusion-positive thyroid cancer who were radioactive iodine-refractory (RAI, if an appropriate treatment option) and had received another prior systemic treatment, and eight patients with RET fusion-positive thyroid cancer who were RAI-refractory and had not received any additional therapy. The ORR for the 19 previously treated patients was 79%. For 87% of patients who had a response to the treatment, their response lasted at least six months. Efficacy was also evaluated in eight patients who had not received therapy other than RAI. The ORR for these patients was 100%. For 75% of patients who had a response to the treatment, their response lasted at least 6 months [5].

Evidence based evaluations