Tecentriq Granted Priority Review to Treat Lung Cancer

The FDA has granted a priority review to a supplemental biologics license application (sBLA) for Tecentriq (atezolizumab) to be used in combination with Avastin (bevacizumab), carboplatin and paclitaxel for the first-line treatment of patients with metastatic nonsquamous non—small cell lung cancer (NSCLC).

The sBLA is a based on findings from the phase 3 IMpower150 trial, in which the Tecentriq regimen demonstrated a median progression-free survival (PFS) of 8.3 months compared with 6.8 months with Avastin and chemotherapy alone. The difference translated into a 38 percent reduction in the hazard for progression or death.

The 12-month PFS rate was 37 percent with the Tecentriq-containing regimen and 18 percent with the Avastin plus chemotherapy regimen. The objective response rate was 64 percent versus 48 percent, respectively.

Genentech, the manufacturer of the PD-L1 inhibitor Tecentriq, reported in March 2018 that the Tecentriq regimen also significantly improved overall survival versus Avastin and chemotherapy alone. The company plans to present these data at an upcoming oncology meeting. The FDA is scheduled to make its decision on the sBLA by Sept. 5, 2018.

“Our phase 3 results showed Tecentriq in combination with Avastin, paclitaxel and carboplatin has the potential to provide a significant survival benefit in the initial treatment of metastatic nonsquamous non—small cell lung cancer,” Sandra Horning, M.D., chief medical officer and head of Global Product Development, Genentech, said in a statement. “We are working closely with the FDA to bring this treatment regimen to people with this type of lung cancer as soon as possible.”

The IMpower150 study enrolled 1202 patients with stage 4 nonsquamous NSCLC. Patients were randomized evenly to receive Tecentriq plus carboplatin and paclitaxel (arm A), Tecentriq with Avastin plus carboplatin and paclitaxel (arm B) or Avastin plus carboplatin and paclitaxel (arm C). Those with known EGFR or ALK alterations were excluded from the study. Patients were also tested for a tumor T-effector gene expression signature.

In the investigational arms, Tecentriq was administered at 1,200 mg intravenously every three weeks and Avastin was given at 15 mg/kg. In each arm, carboplatin and paclitaxel were given on day one of each cycle for four to six cycles. In arm A, maintenance therapy was given with Tecentriq alone and in arm B patients received maintenance therapy with the combination of Avastin and Tecentriq. In arm C, maintenance was given with Avastin alone.

The median age of patients in the trial was 63 years and 60 percent were previous smokers. Overall, most patients were male and the ECOG performance status was 0 for 39 percent of patients in arm B and for 43 percent in arm C. The minimum follow-up at the time of the analysis was 9.5 months. For the interim analysis, the study was only designed to compare arms B and C. Follow-up is continuing for patients in the Tecentriq /chemotherapy arm (arm A), and results will be reported at a later date.

Investigators evaluated multiple biomarker assays as potential ways to enrich for PFS, including the T-effector (Teff) gene signature and PD-L1 expression by the SP142 and SP263 assays. Patients also were screened for EGFR mutations and ALK rearrangements.

Overall the PFS benefit was virtually identical between the intention-to-treat group (692 patients) and biomarker-enriched population (503 patients). The hazard ratios reflected a consistent trend in favor of the Tecentriq arm across all subgroups:

• Teff-high (284 patients) — median PFS, 11.3 versus 6.8 months
• Teff-low (374 patients) — median PFS, 7.3 versus 7.0 months
• PD-L1-high (135 patients) — median PFS, 12.6 versus 6.8 months
• PD-L1-low (224 patients) — median PFS, 8.3 versus 6.6 months
• PD-L1 unknown (338 patients) — median PFS, 7.1 versus 6.9 months

The PD-L1—high subgroup had a 51 percent reduction in the hazard ratio with Tecentriq by the SP142 assay (median PFS, 11.1 vs 6.9 months) and a 50 percent reduction by the SP263 assay (median PFS, 9.1 vs 6.2 months).

For the PD-L1—low subgroup, the hazard ratio with Tecentriq was 0.53 (median PFS, 8.3 vs 6.1 months) by the SP142 assay and 0.57 by the (median PFS, 9.7 vs 6.9 months) by the SP263 assay.

The PD-L1—negative subgroup had a 23 percent reduction in the hazard by the SP142 assay (median PFS, 8.2 vs seven months) and 28 percent by the SP263 assay (median PFS, 7.2 vs 7.0 months).

Patients with EGFR/ALK had a 41 percent reduction in the hazard with Tecentriq and median PFS of 8.7 months versus 6.1 months without Tecentriq. For patients with actionable EGFR mutations, the addition of Tecentriq led to a 59 percent reduction in the hazard ratio (median PFS, 10.2 vs 6.1 months). Patients with liver metastases had a 60 percent reduction in the hazard ratio when they received Tecentriq and a median PFS of 8.2 months versus 5.4 months without Tecentriq.

Each of the agents showed similar toxicity profiles as in previous trials. Serious treatment-related adverse events were observed in 25.4 percent of patients treated with the Tecentriq regimen compared with 19.3 percent of those in the control arm. There were no new safety signals or toxicity issues with this combination.

Tecentriq is currently approved as a treatment for patients with metastatic NSCLC following progression on a platinum-containing regimen, and an FDA-approved targeted therapy for those patients harboring EGFR or ALK abnormalities.