The FDA has granted Priority Review to the supplemental Biologic License Application for atezolizumab as first-line treatment of patients with advanced non-squamous and squamous non-small cell lung cancer without EGFR or ALK mutations with high PD-L1 expression, as determined by PD-L1 biomarker testing.
The FDA has granted Priority Review to the supplemental Biologic License Application (sBLA) for atezolizumab (Tecentriq) as first-line treatment of patients with advanced non-squamous and squamous non-small cell lung cancer (NSCLC) withoutEGFRor ALKmutations with high PD-L1 expression (TC3/IC3 wild-type [WT]), as determined by PD-L1 biomarker testing. The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of target action date of June 19, 2020.
The decision to quickly review the BLA for first-line atezolizumab monotherapy in this patient population was based onresults from the phase III IMpower110 study, which were presented by David R. Spigel, MD, at the 2019 European Society Medical Oncology (ESMO) Annual Meeting.
At a median follow-up of 15.7 months, atezolizumab monotherapy led to an overall survival (OS) of 20.2 months compared with the 13.1-months seen with chemotherapy in patients with high PD-L1 expression (HR, 0.95; 95% CI, 0.3980.890;P=0.0106). Median PFS was 8.1 months (95% CI, 6.8 months-11.0 months) in the atezolizumab group versus 5.0 months (95% CI, 4.2 months -5.7 months) in the chemotherapy group (HR, 0.63; 95% CI, 0.45-0.88; P= .007). In the high PD-L1 population, the confirmed overall response rate (ORR) was 38.3% in the atezolizumab group versus 28.6% in the chemotherapy group. The median duration of response (DOR) was not met in the atezolizumab arm and was 6.7 months in the chemotherapy arm.
"In the IMpower110 study, Tecentriq alone demonstrated a significant improvement in overall survival compared with chemotherapy for people newly diagnosed with certain types of advanced non-small cell lung cancer," said Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, the manufacturer of atezolizumab. "We are working closely with the FDA to bring this chemotherapy-free option to these patients as quickly as possible."
Impower110 is a randomized, open-label study evaluating the efficacy and safety of atezolizumab monotherapy compared with either cisplatin or carboplatin and pemetrexed or gemcitabine patients who are chemotherapy naïve and have advanced non-squamous or squamous NSCLC withoutALKorEGFRmutations (WT).
Overall, the study enrolled 572 people, 555 of whom had WT disease. These patients were randomized 1:1 to either atezolizumab 1200 mg given intravenously on day 1 of each 21-day cycle or chemotherapy. Carboplatin was administered at a dose of AUC5 every 21 days for 4 to 6 cycles. Cisplatin was given at 75 mg/m2doses every 21 days for 4 to 6 cycles. Gemcitabine 1250mg/m2or 1000 mg/m2was administered on days 1 and 8 of each 21-day cycles for 4 to 6 cycles. Pemetrexed was given at 500 mg/m2doses on day 1 of each 21-day cycle. All chemotherapy was administered by intravenous infusion.
The primary end point of the study was OS by PD-L1 subgroup, which was determined by results from the SP142 assay. The key secondary end points were PFS, ORR, and DOR.
Atezolizumab, a monoclonal antibody, has prior indications for NSCLC and small cell lung cancer. The drug is also under investigation in ongoing phase III trials in genitourinary cancers, skin cancers, breast cancer, gastrointestinal cancers, gynecological cancers and head and neck cancers as monotherapy and in combination with other agents.