Genentech announced positive results from the phase III IMpower150 study of Tecentriq (atezolizumab) and Avastin (bevacizumab) plus carboplatin and paclitaxel for the first-line treatment of chemotherapy-naïve people with metastatic non-squamous non-small cell lung cancer.
Genentech is a unit of Roche.
This interim analysis showed that Tecentriq and Avastin plus carboplatin and paclitaxel helped people live significantly longer, compared with Avastin plus carboplatin and paclitaxel (median overall survival = 19.2 versus 14.7 months; hazard ratio = 0.78, 95 percent CI: 0.64-0.96; p=0.016) in the intention-to-treat wild-type population, a co-primary endpoint of the study.
An OS advantage was observed in all pre-specified exploratory biomarker-selected subgroups analyzed, which included people with EGFR- and ALK-positive mutations who had received an appropriate targeted therapy, and those with varying levels of PD-L1 expression or with negative PD-L1 expression.
People with liver metastases treated with the Tecentriq combination also had a survival advantage. The safety profile of the Tecentriq and Avastin plus carboplatin and paclitaxel combination was consistent with the safety profiles of the individual medicines, and no new safety signals were identified with the combination.
At this interim analysis, the combination of Tecentriq plus carboplatin and paclitaxel (Arm A) did not show a statistically significant OS benefit when compared to the combination of Avastin plus carboplatin and paclitaxel (Arm C). Arm A 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.
The combination of Tecentriq and Avastin plus carboplatin and paclitaxel was recently granted Priority Review from the FDA for the first-line treatment of chemotherapy-naïve people with metastatic non-squamous NSCLC. The FDA is expected to make a decision on approval by Sept. 5. IMpower150 is one of eight phase III lung cancer studies underway, evaluating Tecentriq alone or in combination with other medicines. Following the IMpower150 and IMpower131 studies, three more Phase III lung cancer studies are expected to report this year.
IMpower150 is a multicenter, open-label, randomized, controlled phase III study evaluating the efficacy and safety of Tecentriq in combination with chemotherapy (carboplatin and paclitaxel) with or without Avastin in people with stage IV or recurrent metastatic 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 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
Tecentriq 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.
IMpower150 was designed to formally compare Tecentriq plus chemotherapy (Arm A) versus Avastin plus chemotherapy (Arm C), only if Tecentriq and Avastin plus chemotherapy (Arm B) is shown to improve OS in the ITT-WT population compared to Avastin plus chemotherapy (Arm C).
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 3-week treatment cycle for 4 or 6 cycles. People then received maintenance treatment with the Tecentriq 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 EGFR or ALK genetic mutation (intention-to-treat wild-type). Key secondary endpoints included investigator-assessed PFS, OS and safety in the ITT population and in EGFR and ALK mutation subgroups. The study met its co-primary endpoints of OS and PFS per study protocol.
The safety profile of the Tecentriq and Avastin plus carboplatin and paclitaxel combination was consistent with the safety profiles of the individual medicines, and no new safety signals were identified with the combination.
Serious adverse events (grade III-IV) related to treatment were observed in 57 percent of people who received Tecentriq and Avastin plus carboplatin and paclitaxel compared to 49 percent of those who received Avastin plus carboplatin and paclitaxel.
