May 24, 2021: The EMA Committee for Medicinal Products for Human Use (CHMP) has adopted positive opinions for Sanofi and Regeneron’s PD-1 inhibitor Libtayo® (cemiplimab) as monotherapy in two advanced cancers.
The CHMP recommended the approval of Libtayo for the first-line treatment of adults with non-small cell lung cancer (NSCLC) expressing PD-L1 in ≥50% of tumor cells with no EGFR, ALK or ROS1 aberrations.
Patients must have metastatic disease or locally advanced disease that is not a candidate for definitive chemoradiation.
Libtayo was also recommended for approval in adults with locally advanced or metastatic basal cell carcinoma (BCC) who have progressed on or are intolerant to a hedgehog pathway inhibitor (HHI).
The European Commission is expected to make a decision on both indications in the coming months.
The positive opinion for Libtayo in advanced NSCLC is based on results from a Phase 3 trial, which allowed for the enrollment of patients with disease characteristics frequently underrepresented in advanced NSCLC pivotal trials, including those with pre-treated and clinically stable brain metastases or locally advanced NSCLC and who were not candidates for definitive chemoradiation.
Results from the pivotal trial were published in The Lancet in February 2021.
The positive opinion for Libtayo in locally advanced and metastatic BCC is based on results from the largest prospective clinical trial in these patients previously treated with an HHI to date, with data
presented at the European Society for Medical Oncology Virtual Congress 2020 and recently published in The Lancet Oncology. Libtayo is the first immunotherapy to receive a positive CHMP opinion for this indication.
Libtayo is currently approved in the European Union (EU) and other countries for the treatment of certain patients with advanced cutaneous squamous cell carcinoma (CSCC).
About the Phase 3 Trial in Advanced NSCLC
EMPOWER-Lung 1 was an open-label, randomized, multi-center Phase 3 trial designed to investigate Libtayo monotherapy compared to platinum-doublet chemotherapy as first-line treatment in patients with advanced NSCLC who tested positive for PD-L1 in ≥50% of tumor cells and had no EGFR, ALK or ROS1 aberrations.
PD-L1 expression was confirmed using the Agilent Dako PD-L1 IHC 22C3 pharmDx kit.
The primary endpoints were overall survival and progression-free survival, and secondary endpoints included objective response rate (ORR), duration of response (DOR) and quality of life.
In 2020, the trial was stopped early due to significant improvement in overall survival.
The trial randomized 710 patients with either previously untreated metastatic NSCLC (stage IV) or locally advanced NSCLC (stage IIIB/C) who were not candidates for surgical resection or definitive chemoradiation or who had progressed after treatment with definitive chemoradiation.
Among those enrolled, 12% had pre-treated and clinically stable brain metastases and 16% had locally advanced NSCLC that was not a candidate for definitive chemoradiation.
Patients whose disease progressed in the trial were able to change their therapy: those assigned to chemotherapy were allowed to crossover to Libtayo treatment, while those assigned to Libtayo monotherapy were allowed to continue Libtayo treatment and add four cycles of chemotherapy.
There was a >70% crossover rate to Libtayo following disease progression on chemotherapy.
About the Pivotal Trial in Advanced BCC
EMPOWER-BCC 1 was an open-label, multi-center, non-randomized Phase 2 trial of patients with unresectable locally advanced or metastatic BCC (nodal or distant).
Patients in both cohorts had either progressed on HHI therapy, had not had an objective response after nine months on HHI therapy, or were intolerant of prior HHI therapy.
The primary efficacy endpoint was confirmed ORR and a key secondary endpoint was DOR, assessed by independent central review.