Selpercatinib

Unassigned

New Medicines

Medullary RET-mutant thyroid cancer - after prior treatment with cabozantinib or vandetanib

Information

New molecular entity
Eli Lilly
Eli Lilly

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Approved (Licensed)
May 20 · Approved in US. [9]
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 RET-mutant thyroid cancer - after prior treatment with cabozantinib or vandetanib
Oral

Further information

Yes
To be confirmed

Trial or other data

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].

Metastatic RET-fusion non-small cell lung cancer (NSCLC) in adults and children aged 12 years and older after prior treatment with platinum-based chemotherapy

Information

New molecular entity
Eli Lilly
Eli Lilly

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Approved (Licensed)
May 20 · Approved in US. [9]
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].
Metastatic RET-fusion non-small cell lung cancer (NSCLC) in adults and children aged 12 years and older after prior treatment with platinum-based chemotherapy
Oral

Further information

Yes
To be confirmed

Trial or other data

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].

Medullary RET-mutant thyroid cancer - first-line

Information

Licence extension / variation
Eli Lilly
Eli Lilly

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

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 RET-mutant thyroid cancer - first-line
Oral

Metastatic RET-fusion non-small cell lung cancer (NSCLC) - first-line

Information

Licence extension / variation
Eli Lilly
Eli Lilly

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

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].
Metastatic RET-fusion non-small cell lung cancer (NSCLC) - first-line
Oral