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37456211000001106

New Medicines

LibtayoNon-small cell lung cancer (NSCLC), PD-L1-positive - first-line monotherapy

Information

Libtayo
Licence extension / variation
Sanofi
Regeneron

Development and Regulatory status

Launched
Launched
Launched
September 2021
Sep 21Licence extension approved by MHRA, for use as monotherapy for the first-line treatment of adults with non-small cell lung cancer (NSCLC) expressing PD-L1 (in ≥50% tumour cells), with no EGFR, ALK or ROS1 aberrations, who have locally advanced NSCLC who are not candidates for definitive chemoradiation, or metastatic NSCLC [18].
Jun 21Licence extension approved in EU [17].
May 21Recommended for EU approval by CHMP – the new indication is ‘Libtayo as monotherapy is indicated for the first-line treatment of adult patients with non-small cell lung cancer (NSCLC) expressing PD-L1 (in ≥ 50% tumour cells), with no EGFR, ALK or ROS1 aberrations, who have locally advanced NSCLC who are not candidates for definitive chemoradiation, or metastatic NSCLC’ [16].
Feb 21Approved in US [15]
Oct 20US FDA accepts the supplemental Biologics License Application (sBLA) for priority review of cemiplimab for the treatment of patients with first-line locally advanced or metastatic NSCLC with >50% PD-L1 expression. The target action date set by the US FDA decision is February 28, 2021. The sBLA approval is supported by results from a PIII trial that investigated the first-line treatment of cemiplimab monotherapy vs. platinum-doublet chemotherapy in patients with locally advanced or metastatic NSCLC whose tumor cells expressed PD-L1, including those whose cancers had confirmed PD-L1 expression of >50% using the PD-L1 IHC 22C3 pharmDx kit [13].
Sep 20Currently pre-registration in EU [12].
Jul 20Filings now expected 2020 [5].
Apr 20Regulatory submissions in the US and EU now planned in 2020 following positive data from PIII trial.[10]
Oct 19Filings delayed until 2022 [9].
Feb 19Filings now not until 2021 [7].
Mar 18Filings planned for 2019 [4].
Jul 15Regeneron and Sanofi enter into global collaboration to develop and commercialise new antibody anticancer therapies; Regeneron will be the US commercial lead while Sanofi will act as commercial lead outside the US [3].

Category

Programmed cell death-1 protein inhibitor (PDCD-1 antibody)
There were 46,403 new cases of lung cancer diagnosed in the UK in 2014. 53% were males and 47% were females. More than 35,000 people die from the condition. 85% are NSCLC [2].
Non-small cell lung cancer (NSCLC), PD-L1-positive - first-line monotherapy
Intravenous

Further information

Yes

Trial or other data

Feb 21The PIII EMPOWER-Lung 1 RCT found that cemiplimab monotherapy significantly improved survival vs chemotherapy (n=710; median overall survival not yet reached vs 14.2 months; HR, 0.57; p=0.0002: progression-free survival 8.2 vs 5.7 months; HR 0.54; p<0.0001) [14].
Apr 20Primary endpoint of overall survival (OS) met in an open-label, randomized, multi-centre PIII trial (NCT03088540) comparing cemiplimab to platinum-doublet chemotherapy in pts with 1st-line locally advanced or metastatic NSCLC that tested positive for PD-L1 in ≥50% of tumor cells. Pts (n=712) were randomised to receive either cemiplimab 350 mg i.v. every 3 weeks for up to 108 weeks, or platinum-doublet chemotherapy regimen for 4-6 cycles (+/- maintenance pemetrexed). Cemiplimab decreased the risk of death by 32.4% (HR=0.676; CI:0.525-0.870, p=0.002) vs. platinum-doublet chemotherapy. Based on a recommendation by the Independent Data Monitoring Committee to stop the trial early (due to highly significant improvement in overall survival), the trial will be modified to allow all pts to receive cemiplimab. [10,11]
Dec 19PIII trial (NCT03088540) is recruiting; collection of primary outcome data now expected Feb 23 [8].
Nov 18PIII trial (NCT03088540) is recruiting; collection of primary outcome data now expected Sep 22 [6].
May 17PIII trial to assess the safety and efficacy of cemiplimab as first-line treatment in patients with advanced or metastatic NSCLC whose tumors express PD-L1 (NCT03088540). 300 patients will be recruited in Georgia and Turkey. Primary outcome is PFS; collection of these data are due to complete Nov 21 [1].

Evidence based evaluations

LibtayoAdvanced basal cell carcinoma - second-line

Information

Libtayo
Licence extension / variation
Sanofi
Regeneron

Development and Regulatory status

Launched
Launched
Launched
September 2021
Oct 21Use for BCC was also approved by the FDA in Feb 21. In the US it is licensed for the treatment of patients with locally advanced BCC (laBCC) previously treated with a HHI or for whom a HHI is not appropriate, and also treatment of patients with metastatic BCC (mBCC) previously treated with a HHI or for whom a HHI is not appropriate. The mBCC indication was approved under accelerated approval based on tumour response rate and durability of response. Continued approval for mBCC may be contingent upon verification and description of clinical benefit [11].
Sep 21MHRA approves a licence extension for Libtayo, for treatment of adults with locally advanced or metastatic basal cell carcinoma (laBCC or mBCC) who have progressed on or are intolerant to a hedgehog pathway inhibitor (HHI). Sanofi had previously advised that they would not be seeking this licence extension in the UK as currently no HHIs are reimbursed by NHS England [9].
Jun 21Licence extension approved by the EMA for use as monotherapy for the treatment of adults with locally advanced or metastatic basal cell carcinoma (laBCC or mBCC) who have progressed on or are intolerant to a hedgehog pathway inhibitor (HHI). A CHMP positive opinion was issued in May 21 [10].
Jul 19Filings now expected 2020 [5].
Feb 19Still PII; no plans for filing announced yet [4].
Mar 18Filings planned for 2019 [3].

Category

Programmed cell death-1 protein inhibitor (PDCD-1 antibody)
Inconsistent data collection means that accurate figures for the incidence in the UK are difficult to obtain. The reported incidence of BCC in South Wales is 128 per 100,000 for men and 105 per 100,000 for women. There is a regional variation in incidence - eg, approximately 120 per 100,000 in South West England compared with an incidence for the whole of England of approximately 90 per 100,000 population [1].
Advanced basal cell carcinoma - second-line
Intravenous

Trial or other data

Sep 20PII data showed that cemiplimab had a 31% objective response rate, with 85% of patients experiencing on going response at one year [8].
May 20Sanofi and Regeneron report positive topline data from single-arm, open-label trial in patients with advanced BCC who had progressed on or were intolerant to prior hedgehog pathway inhibitor (HHI) therapy.. Study found objective response rate for patients with locally advanced disease was 29%, with an estimated duration of response exceeding one year in 85% of responders [7].
Aug 19PII trial (NCT03132636) is recruiting. Collection of primary outcome data now expected to complete Oct 21 [6].
Jul 17PII study of cemiplimab in patients with advanced BCC who experienced progression of disease on hedgehog pathway inhibitor therapy, or were intolerant of prior hedgehog pathway inhibitor therapy starts (NCT03132636). The trial will enrol approximately 137 patients in the US. Collection of primary outcome data (overall response rate) is due to complete Jun 18 [2].

Evidence based evaluations

LibtayoNon-small cell lung cancer (NSCLC) - first-line in combination with platinum chemotherapy (regardless of histology or PD-L1 status)

Information

Libtayo
Licence extension / variation
Sanofi
Regeneron

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials

Category

Programmed cell death-1 protein inhibitor (PDCD-1 antibody)
There were 46,403 new cases of lung cancer diagnosed in the UK in 2014. 53% were males and 47% were females. More than 35,000 people die from the condition. 85% are NSCLC [1].
Non-small cell lung cancer (NSCLC) - first-line in combination with platinum chemotherapy (regardless of histology or PD-L1 status)
Intravenous

Further information

Yes

Trial or other data

Oct 20PIII EMPOWER 3 study is no longer recruiting; collection of primary outcome data should finish May 23 [4].
Aug 19PIII EMPOWER 3 study (NCT03409614) is recruiting. Collection of primary outcome data is now expected to complete Feb 23 [3].
Mar 18PIII trial starts (NCT03409614). The primary objective is to compare the progression-free survival (PFS) of cemiplimab plus platinum-based doublet chemotherapy combination therapy (cemiplimab/chemo) and cemiplimab plus platinum-based doublet chemotherapy plus ipilimumab combination therapy (cemiplimab/chemo/ipi) with standard-of-care platinum-based doublet chemotherapy in the first-line treatment of patients with advanced squamous or non-squamous non-small cell lung cancer (NSCLC) in the subgroup of patients whose tumors express programmed cell death ligand 1 (PD-L1) in 1% to <50% of tumor cells and in the overall population of study patients whose tumors express PD-L1 in <50% of tumor cells. 690 patients will be recruited in the US, Ireland, Italy, Netherlands, Poland and Thailand. Collection of primary outcome data is due to complete Jul 22 [2].

Evidence based evaluations

LibtayoCervical cancer, recurrent or metastatic platinum-refractory

Information

Libtayo
Licence extension / variation
Sanofi
Regeneron

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Pre-registration (Filed)
Sep 21US FDA accept sBLA for priority review, with a PDUFA date of 30/1/22. EU regulatory submission is planned by end of 21 [11].
Mar 21PIII trial stopped early, filings expected later in 2021 [10].
Jul 20Filings now planned for 2022 [8].
Feb 19Filings now not until 2021 [6].
Mar 18Filings planned for 2020 [4].
Oct 17PIII trial started in US and Australia [1].

Category

Programmed cell death-1 protein inhibitor (PDCD-1 antibody)
Annual incidence of cervical cancer in the UK is currently about 3,200; in England, about a third of patients will have some form of chemotherapy [2].
Cervical cancer, recurrent or metastatic platinum-refractory
Intravenous

Further information

Yes

Trial or other data

Mar 21PIII trial investigating cemiplimab monotherapy compared to chemotherapy in patients previously treated with chemotherapy whose cervical cancer is recurrent or metastatic found overall 31% reduced risk of death. Trial to be stopped early based on recommendation by the Independent Data Monitoring Committee [10].
Jul 20PIII trial (NCT03257267) is no longer recruiting and collection of primary outcome data is expected to complete earlier in May 21 [9].
Jun 19PIII trial (NCT03257267) is still recruiting; collection of primary outcome data now expected to complete Apr 23 [7].
Aug 18PIII trial (NCT03257267 ) is recruiting; collection of primary outcome data now expected to complete Jan 22 [5].
Oct 17NCT03257267 PIII trial initiated in the US and Australia. Patients (est. n=436) with recurrent or metastatic platinum-refractory cervical cancer will be treated with cemiplimab or investigator´s choice of chemotherapy; primary outcome is overall survival and estimated completion date for the primary outcome is May 2020 [3].

Evidence based evaluations

LibtayoCutaneous squamous cell carcinoma (cSCC) - adjuvant therapy

Information

Libtayo
Licence extension / variation
Sanofi
Regeneron

Development and Regulatory status

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

Category

Programmed cell death-1 protein inhibitor (PDCD-1 antibody)
Incidence of SCC is about 10,000 per year in England and Wales. The incidence is higher in Caucasians [1].
Cutaneous squamous cell carcinoma (cSCC) - adjuvant therapy
Intravenous