Merck & Co. Inc. (NYSE:MRK) and Roche (SIX:ROG; OTCQX:RHHBY) each reported survival data from Phase III trials of their checkpoint inhibitors Keytruda pembrolizumab and Tecentriq atezolizumab, respectively, as first-line treatment of squamous non-small cell lung cancer. Both companies reported data in weekend presentations at the American Society of Clinical Oncology (ASCO) meeting in Chicago.
In the KEYNOTE-407 trial, Keytruda plus chemotherapy led to a median overall survival (OS) of 15.9 months vs. 11.3 months for chemo alone (HR=0.64, 95% CI: 0.49, 0.85, p=0.0008). Median progression-free survival (PFS) was 6.4 months for Keytruda plus chemo vs. 4.8 months for chemo alone (HR=0.56, 95% CI: 0.45, 0.7, p<0.0001).
The trial enrolled 559 patients who received no prior systemic therapy for advanced disease to receive carboplatin/paclitaxel or Abraxane nab-paclitaxel alone or in combination with Keytruda. Merck previously reported that Keytruda plus chemo met the primary endpoints of improving OS and PFS in KEYNOTE-407 (see BioCentury Extra, May 23).
An sBLA for the humanized IgG4 mAb against PD-1 is under FDA review for the indication.
Roche's Genentech Inc. unit reported detailed data from the IMpower131 trial, in which the co-primary endpoints evaluated PFS and OS for Tecentriq plus carboplatin and Abraxane vs. the chemo regimen alone in patients with stage IV squamous NSCLC who have not been previously treated with chemo. Tecentriq plus chemo led to a median PFS of 6.3 months vs. 5.6 months for chemo alone (HR=0.71, 95% CI: 0.6, 0.85, p=0.0001). According to ASCO's news release, the Tecentriq combination led to a median OS of 14 months vs. 13.9 months for chemo alone at the interim analysis; the improvement was not significant and the 1,021-patient trial will continue as planned.
Newly released data also showed that the Tecentriq combo let to a 12-month PFS rate of 24.7% and an objective response rate (ORR) of 49% vs. 12% and 41%, respectively, for chemo alone.
Genentech previously reported that Tecentriq plus chemo met the co-primary PFS endpoint vs. chemo alone; a significant OS benefit had not yet been shown as of the interim analysis (see BioCentury Extra, March 20).
IMpower131 is one of eight Phase III lung cancer trials evaluating Tecentriq as a single agent or as a combination therapy. It is a humanized mAb against PD-L1.
In the U.S., Keytruda is approved as monotherapy for first-line treatment of NSCLC in patients with high PD-L1 expression (≥50%) with no EGFR or anaplastic lymphoma kinase (ALK) genomic tumor aberrations; as monotherapy for NSCLC patients whose tumors express PD-L1 (≥1%) with disease progression on or after platinum-containing chemotherapy; and in combination with carboplatin and Alimta pemetrexed as first-line treatment of metastatic non-squamous NSCLC, regardless of PD-L1 expression. The last of the three is an accelerated approval.
Tecentriq is approved in the U.S. and EU to treat metastatic NSCLC in patients whose disease has progressed during or following platinum-containing chemotherapy.