LBA55 - WJOG @Be study: A phase II study of atezolizumab (atez) with bevacizumab (bev) for non-squamous (sq) non-small cell lung cancer (NSCLC) with high PD-L1 expression

Background

In the treatment of advanced NSCLC with PD-1/PD-L1 antibodies, PD-L1 expression in tumor cells is one of the predictive markers for their efficacy. In the first-line treatment for patients with high PD-L1 expression, pembrolizumab or Atez each has been shown to prolong overall survival compared with platinum doublet therapy. On the other hand, Bev enhances the efficacy of cytotoxic agents and EGFR-TKI in non-Sq NSCLC. In addition, preclinical models have shown that Bev also enhances the antitumor activity of PD-1/-PD-L1 antibodies.

Methods

We conducted a single-arm phase II study to investigate clinical benefits of adding Bev 15 mg/kg to Atez 1200 mg/body in the 1st line setting for patients with high PD-L1 expression. Both agents were administered on day 1 q3wk until disease progression. Patients were eligible if they had pathologically confirmed advanced non-Sq NSCLC without any EGFR/ALK/ROS1 alterations, had ECOG performance status 0-1, and PD-L1 expression≥50% detected by Dako 22C3 antibody. The primary endpoint was objective response rate (ORR) assessed by the central review committee (CRC). The sample size was set as 38 assuming that the threshold of ORR was 40% and the expected ORR was 62%. Secondary endpoints were progression free survival (PFS), duration of response, overall survival, and safety.

Results

From August 2018 to January 2020, 40 patients were enrolled from 14 institutions. Of the 40 patients, 33 (83%) were male with a median age of 68 (range: 41-75), 36 (90%) had a history of smoking. One patient was ineligible and did not receive protocol treatment. As of 31 March 2020, none and 25 of the 39 patients were judged as CR and PR, indicating that ORR was 64.1% (95%CI: 47.2-78.8). One year PFS rate was 54.9%. The median number of treatment cycles was 12 (1-27). The treatment was discontinued in 19 patients, 17 and 2 of whose reasons were disease progression and immune-related adverse events, such as sclerosing cholangitis and encephalopathy, respectively. The number of serious adverse events was 23 in 12 patients, but no grade 4/5 toxicity was observed.

Conclusions

This positive result supports Atez with Bev as a potential treatment option for non-Sq NSCLC with high PD-L1 expression.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

West Japan Oncology Group.

Funding

Chugai Pharma.

Disclosure

T. Seto: Honoraria (self): Astellas Pharma; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): Chugai Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Daiichi Sankyo; Honoraria (self), Research grant/Funding (institution): Eli Lilly Japan; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Nippon Boehringer Ingelheim; Honoraria (self), Research grant/Funding (institution): Novartis Pharma; Honoraria (self): Ono Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Pfizer Japan; Honoraria (self): Taiho Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Takeda Pharmaceutical; Honoraria (self): Thermo Fisher Scientific; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Bayer Yakuhin; Research grant/Funding (institution): Kissei Pharmaceutical; Research grant/Funding (institution): Loxo Oncology; Research grant/Funding (institution): Merck Serono; Full/Part-time employment: Precision Medicine Asia. K. Nosaki: Honoraria (self), Honoraria (institution), Research grant/Funding (self), Research grant/Funding (institution): Chugai Pharmaceutical Co., Ltd. R. Toyozawa: Honoraria (self): Kyowa Hakko Kirin; Honoraria (self): Nippon Kayaku; Honoraria (self): Novartis Pharma; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Pfizer Japan; Research grant/Funding (institution): Takeda Pharmaceutical. S. Sugawara: Honoraria (self): Chugai Pharma; Honoraria (self): AstraZeneca; Honoraria (self): MSD; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Nippon Boehringer Ingelheim; Honoraria (self): Eli Lilly and Company; Honoraria (self): Pfizer; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Novartis; Honoraria (self): Kyowa Hakko Kirin. H. Hayashi: Honoraria (self), Research grant/Funding (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (self), Research grant/Funding (institution): Boehringer Ingelheim Japan Inc; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb Co. Ltd.; Honoraria (self), Research grant/Funding (self), Research grant/Funding (institution): Chugai Pharmaceutical Co. Ltd.; Honoraria (self), Research grant/Funding (institution): Eli Lilly Japan K.K; Honoraria (self): Kyorin pharmaceutical co. ltd; Honoraria (self): Merck Biopharma Co., Ltd.; Honoraria (self), Research grant/Funding (institution): MSD K.K; Honoraria (self), Research grant/Funding (institution): Novartis pharmaceuticals k.k; Honoraria (self), Research grant/Funding (self), Research grant/Funding (institution): Ono Pharmaceutical Co. Ltd; Honoraria (self), Research grant/Funding (institution): Pfizer Japan Inc; Honoraria (self): Shanghai Haihe Biopharm; Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical Co. Ltd; Research grant/Funding (institution): Astellas Pharma Inc; Research grant/Funding (institution): Daiichi Sankyo Co., Ltd; Research grant/Funding (institution): Merck Serono Co., Ltd./ Merck Biopharma Co., Ltd; Research grant/Funding (institution): Takeda Pharmaceutical Co., Ltd.; Research grant/Funding (institution): SymBio Pharmaceuticals Limited; Research grant/Funding (institution): AbbVie Inc; Research grant/Funding (institution): inVentiv Health Japan; Research grant/Funding (institution): Icon Japan K.K.; Research grant/Funding (institution): Gritsone Oncology.Inc; Research grant/Funding (institution): Parexel International Corp; Research grant/Funding (institution): Kissei Pharmaceutical Co., Ltd.; Research grant/Funding (institution): EPS Corporation; Research grant/Funding (institution): Syneos Health; Research grant/Funding (institution): Pfizer R&D Japan G.K; Research grant/Funding (institution): A2 Healthcare Corp; Research grant/Funding (institution): Quintiles Inc. / IQVIA Services Japan K.K.; Research grant/Funding (institution): EP-CRSU Co., Ltd., Linical Co., Ltd., Eisai Co., Ltd., CMIC Shift Zero K.K., Kyowa Hakko Kirin Co., Ltd., Bayer Yakuhin, Ltd., EPS International Co., Ltd,., Otsuka Pharmaceutical Co., Ltd.,. H. Murakami: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Chugai pharma; Honoraria (self), Research grant/Funding (institution): Lilly Japan; Honoraria (self): Taiho Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Takeda; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Bristol-Myers Squibb Japan; Honoraria (self): MSD; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): IQVIA. T. Kato: Honoraria (self), Research grant/Funding (institution): Chugai. S. Niho: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Honoraria (self): MSD; Honoraria (self): Boehringer Ingelheim; Research grant/Funding (institution): Merck Biopharma; Research grant/Funding (institution): Chugai. H. Saka: Honoraria (self): Chugai; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Ono; Honoraria (self): Boehringer Ingelheim Japan; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Taisho-Toyama. H. Yoshioka: Honoraria (self), Lecture fee: Chugai pharmaceutical. I. Okamoto: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Chugai. H. Daga: Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self): MSD; Honoraria (self), Research grant/Funding (institution): Astrazeneca; Honoraria (self): Ono. K. Azuma: Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: Chugai phrma; Speaker Bureau/Expert testimony: Bristol-meiers squib; Speaker Bureau/Expert testimony: Ono Pharma. H. Tanaka: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Bristol Myers Squibb; Honoraria (self), Research grant/Funding (institution): Boehringer-ingelheim; Honoraria (self), Research grant/Funding (institution): Chugai Pharmaceutical; Research grant/Funding (institution): Ono Pharmaceutical; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Pfizer. K. Nishino: Honoraria (self): AstraZeneca; Honoraria (self): Chugai; Honoraria (self): Eli Lilly Japan; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Ono; Honoraria (self): Nippon Boehringer Ingelheim. M. Satouchi: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self): Taiho; Honoraria (self): Nippon kayaku; Honoraria (self), Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): Ono; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Honoraria (self), Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Ignyta; Research grant/Funding (institution): Takeda. N. Yamamoto: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD K.K.; Honoraria (self), Research grant/Funding (institution): AstraZeneca K.K; Honoraria (self): Ono Pharmaceutical Co., Ltd; Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical Co., Ltd.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Takeda Pharmaceutical Co., Ltd.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Chugai Pharmaceutical Co., Ltd.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly Japan K.K; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Japan Boehringer-Ingelheim Co., Ltd; Honoraria (self), Research grant/Funding (institution): Nipponkayaku; Honoraria (self), Research grant/Funding (institution): Novartis Pharma K.K.; Honoraria (self), Research grant/Funding (institution): Pfizer Inc.; Research grant/Funding (institution): Astellas Amgen BioPharma; Research grant/Funding (institution): Tsumura; Research grant/Funding (institution): Daiichi Sankyo Company; Research grant/Funding (institution): Shionogi; Research grant/Funding (institution): Toppan printing; Research grant/Funding (institution): Tosoh Corporation. K. Nakagawa: Honoraria (self), Research grant/Funding (institution): AstraZeneca K.K.; Honoraria (self): Nichi-Iko Pharmaceutical Co., Ltd; Honoraria (self), Research grant/Funding (institution): Astellas Pharma Inc; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Takeda Pharmaceutical Co.,Ltd; Honoraria (self), Research grant/Funding (institution): MSD K.K.; Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical Co., Ltd.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (institution): Bristol Myers Squibb Company; Honoraria (self), Research grant/Funding (institution): Nippon Boehringer Ingelheim Co., Ltd.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly Japan K.K.; Honoraria (self), Research grant/Funding (institution): Novartis Pharma K.K; Honoraria (self), Research grant/Funding (institution): SymBio Pharmaceuticals Limited; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer Japan Inc; Honoraria (self), Research grant/Funding (institution): Chugai Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (institution): Daiichi Sankyo Co., Ltd; Honoraria (self), Advisory/Consultancy: Kyorin Pharmaceutical Co., Ltd.; Honoraria (self): Thermo Fisher Scientific K.K.; Honoraria (self): Roche Diagnostics K.K.; Honoraria (self): Nippon Kayaku Co., Ltd.; Honoraria (self), Research grant/Funding (institution): Bayer Yakuhin, Ltd; Honoraria (self), Research grant/Funding (institution): Merck Biopharma Co., Ltd; Honoraria (self), Research grant/Funding (institution): AbbVie Inc; Research grant/Funding (institution): Eisai Co., Ltd; Research grant/Funding (institution): Kissei Pharmaceutical Co., Lt; Research grant/Funding (institution): Kyowa Hakko Kirin Co., Ltd; Research grant/Funding (institution): Otsuka Pharmaceutical Co., Ltd.; Research grant/Funding (institution): Pfizer R&D Japan G.K.; Honoraria (self): Clinical Trial Co., Ltd., Nanzando Co., Ltd., Medicus Shuppan, Publishers Co., Ltd., Yodosha Co., Ltd., Care Net, Inc, Nikkei Business Publications, Inc, Reno, Medical K.K. Medical Review Co., Ltd., Yomiuri Telecasting Corporation, Medical Mobile Communications; Research grant/Funding (institution): A2 Healthcare Corp., inVentiv Health Japan, Quintiles Inc., IQVIA Services Japan K.K./icon Japan K.K./ EP-Crsu Co., Ltd./Gritsone Oncology.Inc, Linical Co., Ltd./Parexel International Corp., CMIC Shift Zero K.K./ EPS Corporation, Syneos Health, EPS Interna. All other authors have declared no conflicts of interest.