Genentech’s Phase III IMpower150 study met its co-primary endpoint of overall survival (OS) at this interim analysis and showed that initial (first-line) treatment with the combination of Tecentriq (atezolizumab) and Avastin (bevacizumab) plus carboplatin and paclitaxel (chemotherapy) helped people with advanced non-squamous non-small cell lung cancer (NSCLC) live significantly longer compared with Avastin plus carboplatin and paclitaxel. A survival benefit was observed across key subgroups, including those with varying levels of PD-L1 expression.
Safety for the Tecentriq and Avastin plus carboplatin and paclitaxel combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combinations. These data will be presented at an upcoming oncology congress.
“We are pleased that the IMpower150 study demonstrated a clinically meaningful survival benefit for people receiving their initial treatment for this type of advanced lung cancer,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “These results add to the growing body of evidence supporting the role of combining Tecentriq with Avastin. We will submit these additional data to global health authorities and hope to bring this potential treatment option to patients as soon as possible.”
At this interim analysis, the study found that substituting Avastin with Tecentriq in the combination with carboplatin and paclitaxel did not show a statistically significant OS benefit in people with advanced NSCLC compared to a combination of Avastin plus carboplatin and paclitaxel. The study will continue as planned to the final analysis. Safety in the Tecentriq plus carboplatin and paclitaxel arm appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination.
Previously reported results from the IMpower150 study showed that the combination of Tecentriq and Avastin plus carboplatin and paclitaxel reduced the risk of disease worsening or death (progression-free survival; PFS), a co-primary endpoint, by 38 percent (HR=0.62; p<0.0001, 95 percent CI: 0.52-0.74) compared to Avastin plus carboplatin and paclitaxel in the first-line treatment of people with advanced non-squamous NSCLC. This PFS benefit was observed across key subgroups, including those with varying levels of PD-L1 expression.
IMpower150 is one of eight Phase III lung cancer studies underway, evaluating Tecentriq alone or in combination with other medicines. Following the positive IMpower150 and IMpower131 studies, three more Phase III lung cancer studies are expected to report this year.
About the IMpower150 study
IMpower150 is a multicenter, open-label, randomized, controlled Phase III study evaluating the efficacy and safety of Tecentriq in combination with carboplatin and paclitaxel with or without Avastin in people with stage IV non-squamous NSCLC who had not been treated with chemotherapy for their advanced disease. It enrolled 1,202 people, of which those with ALK and EGFR mutations were excluded from the primary intention-to-treat (ITT) analysis. People were randomized (1:1:1) to receive:
- Tecentriq plus carboplatin and paclitaxel (Arm A), or
- Tecentriq and Avastin plus carboplatin and paclitaxel (Arm B), or
- Avastin plus carboplatin and paclitaxel (Arm C, control arm).
During the treatment-induction phase, people in Arm A received Tecentriq administered intravenously at 1200 mg in combination with intravenous infusion of carboplatin and paclitaxel on Day 1 of a 3-week treatment cycle for 4 or 6 cycles. Following the induction phase, people received maintenance treatment with Tecentriq (1200 mg every 3 weeks) until loss of clinical benefit or disease progression.
People in Arm B received induction treatment with Tecentriq (1200 mg) and Avastin administered intravenously at 15 mg/kg in combination with intravenous infusion of carboplatin and paclitaxel on Day 1 of a three week treatment cycle for four or six cycles. People then received maintenance treatment with the Tecebtriq and Avastin regimen until disease progression (Avastin) or loss of clinical benefit/disease progression (Tecentriq).
People in Arm C received induction treatment with Avastin administered intravenously at 15 mg/kg plus intravenous infusion of carboplatin and paclitaxel on Day 1 of a 3-week treatment cycle for 4 or 6 cycles. This was followed by maintenance treatment with Avastin alone until disease progression.
The co-primary endpoints were PFS and OS, as determined by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). The co-primary OS endpoint in IMpower150 was assessed in all randomized people without an ALK or EGFR genetic mutation (intention-to-treat wild-type). Key secondary endpoints included investigator-assessed PFS and OS, safety in the ITT population and in EGFR and ALK mutation subgroups.
The primary analysis of the co-primary PFS endpoint in IMpower150 was assessed in two populations: all randomized people without an ALK or EGFR genetic mutation (intention-to-treat wild-type) and in a subgroup of people who had a specific biomarker (T-effector “Teff” gene signature expression). IMpower150 met its PFS co-primary endpoint per study protocol for both populations assessed.
(Source: Genentech)
Filed Under: Drug Discovery
