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Randomised efficacy and safety results for atezolizumab (Atezo) + bevacizumab (Bev) in patients (pts) with previously untreated, unresectable hepatocellular carcinoma (HCC)
abstracts
Annals of Oncology membership: Genentech/Roche; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): AstraZeneca. D. Begic: Full / Part-time employment: Bristol-Myers Squibb. J. Neely: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. J. Anderson: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. B. Sangro: Advisory / Consultancy: Adaptimmune; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: BTG; Advisory / Consultancy: H3 Biomedicine; Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Advisory / Consultancy: Lilly; Advisory / Consultancy: Merck; Advisory / Consultancy: Onxeo; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Sirtex Medical; Advisory / Consultancy: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Terumo. All other authors have declared no conflicts of interest.
Randomised efficacy and safety results for atezolizumab (Atezo) 1 bevacizumab (Bev) in patients (pts) with previously untreated, unresectable hepatocellular carcinoma (HCC)
M. Lee1, B-Y. Ryoo2, C-H. Hsu3, K. Numata4, S. Stein5, W. Verret6, S. Hack6, J. Spahn6, B. Liu7, H. Abdullah8, R. He9, K-H. Lee10 1 UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 2Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, 3Department of Oncology, National Taiwan University Hospital, Taipei City, Taiwan, 4Department of Gastroenterology, Yokohama City University Medical Center, Yokohama, Japan, 5 Medical Oncology, Yale School of Medicine, New Haven, CT, USA, 6Product Development - Oncology, Genentech, Inc., South San Francisco, CA, USA, 7Biostatistics. PDBB, Genentech, Inc., South San Francisco, CA, USA, 8Safety Science Oncology, Genentech, Inc., South San Francisco, CA, USA, 9Department of Medicine, Georgetown University Medical Center, Washington, DC, USA, 10Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea Background: Pts with unresectable HCC have few treatment (tx) options. Checkpoint inhibitors and combination approaches with anti-VEGFs are emerging as potential new tx options. Here we report the first randomised dataset evaluating atezo (anti-PDL1) as monotherapy vs the combination of atezo þ bev (anti-VEGF; Arm F) as well as updated single-arm atezo þ bev data (Arm A) from a Ph 1b study. Methods: Arms F and A of the Ph 1b study GO30140 enrolled systemic tx-naı¨ve pts with unresectable HCC. Arm F pts were randomised 1:1 to atezo þ bev or atezo monotherapy and received atezo 1200 mg IV q3w, bev 15 mg/kg IV q3w until unacceptable toxicity or loss of clinical benefit. Arm A pts received atezo þ bev. Primary endpoints
Disclosure: M. Lee: Research grant / Funding (self): Amgen; Research grant / Funding (self): BristolMyers Squibb ; Research grant / Funding (self): Pfizer; Research grant / Funding (self): EMD Serono; Research grant / Funding (self): Genentech/Roche. C. Hsu: Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (institution), Advisory / Consultancy: Ono Pharmaceutical; Honoraria (institution), Research grant / Funding (self): MSD; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: AZ; Advisory / Consultancy: Roche. S. Stein: Advisory / Consultancy: Genentech; Advisory / Consultancy: BMS; Advisory / Consultancy: Eisai; Advisory / Consultancy: Bayer; Advisory / Consultancy: Exelixis. W. Verret: Full / Part-time employment: Genentech/Roche. S. Hack: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech/Roche. J. Spahn: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech/Roche. B. Liu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech/Roche. H. Abdullah: Full / Part-time employment: Genentech/Roche. R. He: Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: Eisai Inc.; Speaker Bureau / Expert testimony: Exelixis Inc; Advisory / Consultancy, Research grant / Funding (institution): Merck & Co; Advisory / Consultancy: AZ. K. Lee: Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self): Bayer; Honoraria (self): Eisai; Honoraria (self): Ono Pharmaceuticals; Honoraria (self), Speaker Bureau / Expert testimony: Roche; Honoraria (self): Samsung Bioepis; Speaker Bureau / Expert testimony: Eli Lilly. All other authors have declared no conflicts of interest.
Table: LBA39 Arm F IRF RECIST 1.1
Median follow-up, mo Median PFS, mo 95% CI HR 80% CI
Median follow-up, mo Confirmed ORR, n (%) 95% CI (%) Complete Response (CR), n (%) Partial Response (PR), n (%) On-going response, n (%) DCR (CR þ PR þ SD), n (%) Median DOR, mo 95% CI Median PFS, mo 95% CI
IRF HCC mRECIST
F1 Atezo þ Bev (n ¼ 60)
F2 Atezo (n ¼ 59)
6.6 5.6b 3.6 – 7.4 0.55b 0.40 – 0.74 P ¼ 0.0108 Arm A: Atezo þ Bev n ¼ 104 IRF RECIST 1.1 12.4 37 (36)b 26 – 46 12 (12) 25 (24) 28 (76) 74 (71) NE 11.8 – NE 7.3 5.4 – 9.9
6.7 3.4b 1.9 – 5.2
a
F1 Atezo þ Bev (n ¼ 60)
F2 Atezo (n ¼ 59)a
6.6 5.6 3.6 – 7.4 0.54 0.40 – 0.74
6.7 3.4 1.9 – 5.2
IRF HCC mRECIST 41 (39) 30 – 50 16 (15) 25 (24) 28 (68) 74 (71) NE 11.8 – NE 7.3 5.4 – 9.9
DCR, disease control rate; DOR, duration of response; NE, not estimable; SD, stable disease. Data cut off: 14 June 2019. a 1 randomised pt did not receive atezo. b Primary endpoint.
Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz394 | v875
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz394.030/5577908 by guest on 24 October 2019
LBA39
were progression free survival (PFS; Arm F) and objective response rate (ORR, Arm A) by independent review facility (IRF)-assessed RECIST 1.1, and safety (Arms F and A). Results: In Arm F, 60 pts were randomised to atezo þ bev (Group F1) and 59 pts to atezo (Group F2). Arm F showed a statistically significant improvement in the primary endpoint median PFS for atezo þ bev vs atezo (5.6 vs 3.4 mo, HR 0.55, 80% CI, 0.40 – 0.74, P ¼ 0.0108). Any-Gr TRAEs occurred in 41 (68%) F1 pts and 24 (41%) F2 pts; Gr 3-4 TRAEs occurred in 12 (20%) F1 pts and 3 (5%) F2 pts. There were no Gr 5 TRAEs in Arm F. For the 104 pts in Arm A, primary endpoint ORR was 36% (37 pts) with 76% ongoing. Any-Grade (Gr) tx-related adverse events (TRAEs) occurred in 91 (88%) pts; Gr 3-4 TRAEs occurred in 41 (39%) pts. Gr 5 TRAEs were seen in 3 (3%) pts. Conclusions: By meeting its primary endpoint of improved PFS for atezo þ bev vs atezo alone, Arm F showed the single-agent contribution of atezo and bev to the overall tx effect. With longer follow up, Arm A highlights the clinically meaningful and durable responses of atezo þ bev. Coupled with a tolerable safety profile, these data suggest that atezo þ bev is a promising first-line tx option for unresectable HCC. Clinical trial identification: NCT02715531. Editorial acknowledgement: Medical writing assistance was provided by Steffen Biechele, PhD, of Health Interactions and funded by F. Hoffmann-La Roche, Ltd. Legal entity responsible for the study: F. Hoffmann-La Roche, Ltd. Funding: F. Hoffmann-La Roche, Ltd.
Annals of Oncology membership: Genentech/Roche; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): AstraZeneca. D. Begic: Full / Part-time employment: Bristol-Myers Squibb. J. Neely: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. J. Anderson: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. B. Sangro: Advisory / Consultancy: Adaptimmune; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: BTG; Advisory / Consultancy: H3 Biomedicine; Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Advisory / Consultancy: Lilly; Advisory / Consultancy: Merck; Advisory / Consultancy: Onxeo; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Sirtex Medical; Advisory / Consultancy: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Terumo. All other authors have declared no conflicts of interest.
Randomised efficacy and safety results for atezolizumab (Atezo) 1 bevacizumab (Bev) in patients (pts) with previously untreated, unresectable hepatocellular carcinoma (HCC)
M. Lee1, B-Y. Ryoo2, C-H. Hsu3, K. Numata4, S. Stein5, W. Verret6, S. Hack6, J. Spahn6, B. Liu7, H. Abdullah8, R. He9, K-H. Lee10 1 UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 2Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, 3Department of Oncology, National Taiwan University Hospital, Taipei City, Taiwan, 4Department of Gastroenterology, Yokohama City University Medical Center, Yokohama, Japan, 5 Medical Oncology, Yale School of Medicine, New Haven, CT, USA, 6Product Development - Oncology, Genentech, Inc., South San Francisco, CA, USA, 7Biostatistics. PDBB, Genentech, Inc., South San Francisco, CA, USA, 8Safety Science Oncology, Genentech, Inc., South San Francisco, CA, USA, 9Department of Medicine, Georgetown University Medical Center, Washington, DC, USA, 10Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea Background: Pts with unresectable HCC have few treatment (tx) options. Checkpoint inhibitors and combination approaches with anti-VEGFs are emerging as potential new tx options. Here we report the first randomised dataset evaluating atezo (anti-PDL1) as monotherapy vs the combination of atezo þ bev (anti-VEGF; Arm F) as well as updated single-arm atezo þ bev data (Arm A) from a Ph 1b study. Methods: Arms F and A of the Ph 1b study GO30140 enrolled systemic tx-naı¨ve pts with unresectable HCC. Arm F pts were randomised 1:1 to atezo þ bev or atezo monotherapy and received atezo 1200 mg IV q3w, bev 15 mg/kg IV q3w until unacceptable toxicity or loss of clinical benefit. Arm A pts received atezo þ bev. Primary endpoints
Disclosure: M. Lee: Research grant / Funding (self): Amgen; Research grant / Funding (self): BristolMyers Squibb ; Research grant / Funding (self): Pfizer; Research grant / Funding (self): EMD Serono; Research grant / Funding (self): Genentech/Roche. C. Hsu: Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (institution), Advisory / Consultancy: Ono Pharmaceutical; Honoraria (institution), Research grant / Funding (self): MSD; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: AZ; Advisory / Consultancy: Roche. S. Stein: Advisory / Consultancy: Genentech; Advisory / Consultancy: BMS; Advisory / Consultancy: Eisai; Advisory / Consultancy: Bayer; Advisory / Consultancy: Exelixis. W. Verret: Full / Part-time employment: Genentech/Roche. S. Hack: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech/Roche. J. Spahn: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech/Roche. B. Liu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech/Roche. H. Abdullah: Full / Part-time employment: Genentech/Roche. R. He: Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: Eisai Inc.; Speaker Bureau / Expert testimony: Exelixis Inc; Advisory / Consultancy, Research grant / Funding (institution): Merck & Co; Advisory / Consultancy: AZ. K. Lee: Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self): Bayer; Honoraria (self): Eisai; Honoraria (self): Ono Pharmaceuticals; Honoraria (self), Speaker Bureau / Expert testimony: Roche; Honoraria (self): Samsung Bioepis; Speaker Bureau / Expert testimony: Eli Lilly. All other authors have declared no conflicts of interest.
Table: LBA39 Arm F IRF RECIST 1.1
Median follow-up, mo Median PFS, mo 95% CI HR 80% CI
Median follow-up, mo Confirmed ORR, n (%) 95% CI (%) Complete Response (CR), n (%) Partial Response (PR), n (%) On-going response, n (%) DCR (CR þ PR þ SD), n (%) Median DOR, mo 95% CI Median PFS, mo 95% CI
IRF HCC mRECIST
F1 Atezo þ Bev (n ¼ 60)
F2 Atezo (n ¼ 59)
6.6 5.6b 3.6 – 7.4 0.55b 0.40 – 0.74 P ¼ 0.0108 Arm A: Atezo þ Bev n ¼ 104 IRF RECIST 1.1 12.4 37 (36)b 26 – 46 12 (12) 25 (24) 28 (76) 74 (71) NE 11.8 – NE 7.3 5.4 – 9.9
6.7 3.4b 1.9 – 5.2
a
F1 Atezo þ Bev (n ¼ 60)
F2 Atezo (n ¼ 59)a
6.6 5.6 3.6 – 7.4 0.54 0.40 – 0.74
6.7 3.4 1.9 – 5.2
IRF HCC mRECIST 41 (39) 30 – 50 16 (15) 25 (24) 28 (68) 74 (71) NE 11.8 – NE 7.3 5.4 – 9.9
DCR, disease control rate; DOR, duration of response; NE, not estimable; SD, stable disease. Data cut off: 14 June 2019. a 1 randomised pt did not receive atezo. b Primary endpoint.
Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz394 | v875
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz394.030/5577908 by guest on 24 October 2019
LBA39
were progression free survival (PFS; Arm F) and objective response rate (ORR, Arm A) by independent review facility (IRF)-assessed RECIST 1.1, and safety (Arms F and A). Results: In Arm F, 60 pts were randomised to atezo þ bev (Group F1) and 59 pts to atezo (Group F2). Arm F showed a statistically significant improvement in the primary endpoint median PFS for atezo þ bev vs atezo (5.6 vs 3.4 mo, HR 0.55, 80% CI, 0.40 – 0.74, P ¼ 0.0108). Any-Gr TRAEs occurred in 41 (68%) F1 pts and 24 (41%) F2 pts; Gr 3-4 TRAEs occurred in 12 (20%) F1 pts and 3 (5%) F2 pts. There were no Gr 5 TRAEs in Arm F. For the 104 pts in Arm A, primary endpoint ORR was 36% (37 pts) with 76% ongoing. Any-Grade (Gr) tx-related adverse events (TRAEs) occurred in 91 (88%) pts; Gr 3-4 TRAEs occurred in 41 (39%) pts. Gr 5 TRAEs were seen in 3 (3%) pts. Conclusions: By meeting its primary endpoint of improved PFS for atezo þ bev vs atezo alone, Arm F showed the single-agent contribution of atezo and bev to the overall tx effect. With longer follow up, Arm A highlights the clinically meaningful and durable responses of atezo þ bev. Coupled with a tolerable safety profile, these data suggest that atezo þ bev is a promising first-line tx option for unresectable HCC. Clinical trial identification: NCT02715531. Editorial acknowledgement: Medical writing assistance was provided by Steffen Biechele, PhD, of Health Interactions and funded by F. Hoffmann-La Roche, Ltd. Legal entity responsible for the study: F. Hoffmann-La Roche, Ltd. Funding: F. Hoffmann-La Roche, Ltd.