- Email: [email protected]
Overall survival (OS) from the AURA3 phase III study: Osimertinib vs platinum-pemetrexed (plt-pem) in patients (pts) with EGFR T790M advanced non-small cell lung cancer (NSCLC) and progression on a prior EGFR-tyrosine kinase inhibitor (TKI)
abstracts
475O
Overall survival (OS) from the AURA3 phase III study: Osimertinib vs platinum-pemetrexed (plt-pem) in patients (pts) with EGFR T790M advanced non-small cell lung cancer (NSCLC) and progression on a prior EGFR-tyrosine kinase inhibitor (TKI)
Y-L. Wu1, T.S.K. Mok2, J-Y. Han3, M-J. Ahn4, A. Delmonte5, S.S. Ramalingam6, S-W. Kim7, F.A. Shepherd8, J. Laskin9, Y. He10, H. Akamatsu11, W.S.M.E. Theelen12, W-C. Su13, T. John14, M. Sebastian15, H. Mann16, M. Miranda16, G. Laus17, Y. Rukazenkov18, V. Papadimitrakopoulou19 1 Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China, 2Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong, China, 3Center for Lung Cancer, National Cancer Center, Goyang, Republic of Korea, 4Department of Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, 5Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy, 6 Department of Hematology and Medical Oncology, Emory University School of Medicine Winship Cancer Institute, Atlanta, USA, 7Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, 8 Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, ON, Canada, 9 Department of Medicine, BC Cancer Agency, Vancouver, BC, Canada, 10Department of Respiratory Disease, Daping Hospital, Chongqing, China, 11Internal Medicine III, Wakayama Medical University Hospital, Wakayama, Japan, 12Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands, 13Department of Oncology, National Cheng Kung University Hospital, Tainan, Taiwan, 14Department of Medical Oncology, Olivia Newton-John Cancer Research Institute, Melbourne, Australia, 15 Department of Hematology/Medical Oncology, University Hospital Frankfurt, Frankfurt am Main, Germany, 16Oncology R&D, AstraZeneca, Cambridge, UK, 17Global Medicines Development, AstraZeneca, Cambridge, UK, 18Global Medicines Development, AstraZeneca, Cambridge, UK, 19Department of Thoracic Head and Neck Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA Background: In AURA3 (NCT02151981), osimertinib, a 3rd-generation EGFR-TKI, significantly prolonged progressionfree survival (PFS) and improved response rate vs plt-pem in pts with centrally confirmed EGFR T790M advanced NSCLC and progression on a prior EGFR-TKI. Here we report mature OS data. Methods: Adult pts were randomised 2:1 to receive oral osimertinib (80 mg once daily) or intravenous pem (500 mg per m2 of body surface area) þ carboplatin (target area under the curve 5)/cisplatin (75 mg per m2), every 3 weeks, 6 cycles. Treatment beyond progression (RECIST 1.1) was allowed if clinical benefit continued. Pts receiving plt-pem could cross over to osimertinib on disease progression. Asymptomatic CNS metastases were allowed. Primary endpoint was investigator-assessed PFS. OS and safety are reported as secondary endpoints. Data cut-off (DCO): 15 March 2019. Results: In total, 419 pts were randomised (osimertinib, n ¼ 279; plt-pem, n ¼ 140); 99 pts (71%) crossed over to osimertinib from plt-pem. At DCO, 188 pts (67%) in the osimertinib arm vs 93 pts (66%) in the plt-pem arm had died, including 66/99 (67%) crossover pts; median OS 26.8 mo (95% confidence interval [CI] 23.5, 31.5) vs 22.5 mo (95% CI 20.2, 28.8) respectively, hazard ratio (HR) 0.87 (95% CI 0.67, 1.12; p ¼ 0.277); survival rate at 24 mo was 55% vs 43% and at 36 mo was 37% vs 30%. Time to first subsequent treatment showed a large, clinically meaningful numerical advantage towards osimertinib, HR 0.21 (95% CI 0.16, 0.28; p < 0.001); time to second subsequent treatment, HR 0.87 (95% CI 0.69, 1.11; p ¼ 0.263). In both arms, 99% pts had any adverse event (AE). Any AE grade 3 causally related to study treatment was 9% vs 34% for osimertinib and plt-pem respectively. Most common AEs were diarrhoea, 44% (grade 3, 1%), and nausea, 49% (grade 3, 4%), with osimertinib and plt-pem respectively. Conclusions: A numerical advantage in OS was observed for pts receiving osimertinib vs plt-pem, with the majority of pts in the plt-pem arm having crossed over to osimertinib. The safety profile of osimertinib remains consistent with previous findings. Clinical trial identification: NCT02151981. Editorial acknowledgement: Laura Crocker, BMedSci, of iMed Comms, an Ashfield Company, who provided medical writing support funded by AstraZeneca. Legal entity responsible for the study: AstraZeneca.
ix158 | Thoracic tumours, metastatic
Funding: AstraZeneca. Disclosure: Y-L. Wu: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self): Eli Lilly; Honoraria (self): Pfizer; Honoraria (self): MSD; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim. T.S.K. Mok: Honoraria (self): ACEA Pharma, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., LTD., AstraZeneca (before 1/1/19), Bayer, BI, Blueprint Medicines Corporation, BMS, Celgene, CStone Pharmaceuticals, Eli Lilly, Fishawack Facilitate Ltd, Hengrui Therapeutics Inc., Ignyt; Advisory / Consultancy: ACEA Pharma, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., LTD., AstraZeneca (before 1/1/19), Bayer, BI, Blueprint Medicines Corporation, BMS, Celgene, Cirina, CStone Pharmaceuticals, Eli Lilly, Fishawack Facilitate Ltd, geneDecode Co., Ltd. (un; Leadership role: AstraZeneca PLC, Hutchison Chi-Med; Research grant / Funding (institution): AstraZeneca, BMS, Clovis Oncology, MSD, Novartis, Pfizer, Roche, SFJ, XCovery; Shareholder / Stockholder / Stock options: Shareholder: Hutchison Chi-Med, Sanomics Ltd. Stock option: Clearbridge Biomedics (now Biolidics Ltd.), Loxo-Oncology, OrigiMed Co. Ltd., Virtus Medical Group; Full / Part-time employment: The Chinese University of Hong Kong; Officer / Board of Directors: Remunerated: AstraZeneca PLC, Hutchison Chi-Med Non-remunerated: American Society of Clinical Oncology (ASCO) Asian Thoracic Oncology Research Group (ATORG) Chinese Lung Cancer Research Foundation Limited (CLCRF) Chinese Society of Clinical Oncology (CS. J-Y. Han: Honoraria (self): Roche, AstraZeneca, Bristol-Myers Squibb, MSD, Takeda; Advisory / Consultancy: AstraZeneca, Bristol-Myers Squibb, MSD, Takeda, Pfizer, Novartis, Lilly; Research grant / Funding (self): Roche, Pfizer, Ono Pharmaceutical, Takeda. M-J. Ahn: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca, Merck, Sharp & Dohme, Ono Pharmaceutical, Lilly, Roche; Advisory / Consultancy: Alpha Pharmaceutical, Takeda. S.S. Ramalingam: Honoraria (self), Advisory / Consultancy: AstraZeneca, Amgen, Bristol-Myers Squibb, Merck, Roche/Genentech, Loxo, Nektar, Tesaro; Research grant / Funding (institution): AstraZeneca, Amgen, Bristol-Myers Squibb, Merck, Tesaro, Advaxis, Takeda. S-W. Kim: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca. F.A. Shepherd: Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: AstraZeneca. J. Laskin: Research grant / Funding (institution): AstraZeneca, Roche, Boehringer Ingelheim, Pfizer; Honoraria (self): AstraZeneca, Roche, Pfizer. H. Akamatsu: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Honoraria (institution): Chugai; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Pfizer; Honoraria (self), Honoraria (institution): Boehringer Ingelheim. W-C. Su: Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Boehringer Ingelheim. T. John: Advisory / Consultancy: Roche, Bristol-Myers Squibb, Merck, Ignyta, AstraZeneca, Takeda, Boehringer Ingelheim, Pfizer. M. Sebastian: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca, Roche, Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer, Boehringer Ingelheim, Celgene, Takeda, Bristol-Myers Squibb, MSD; Honoraria (self), Advisory / Consultancy: Lilly. H. Mann: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. M. Miranda: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. G. Laus: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. Y. Rukazenkov: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. V. Papadimitrakopoulou: Honoraria (self): F Hoffman-La Roche; Advisory / Consultancy: Nektar Therapeutics, AstraZeneca Pharmaceuticals, Arrys Therapeutics, Merck&Co, LOXO Oncology, Araxes Pharma, F.Hoffman-LaRoche Ltd, Janssen Research Foundation, Bristol-Myers Squibb, Clovis Oncology, Eli Lilly &Co, Novartis Pharmaceuticals Corp. Takeda ; Research grant / Funding (institution): Eli Lilly &Co, Novartis, Merck, AstraZeneca Pharmaceuticals, F Hoffman-La Roche, Nektar Therapeutics, Janssen, Bristol-Myers Squibb, Checkmate, Incyte. All other authors have declared no conflicts of interest.
476O
A phase I study to evaluate safety and efficacy of BPI-7711 in EGFRm1/T790M1 advanced or recurrent NSCLC patients
Y. Shi1, J. Fang2, Y. Shu3, D. Wang4, H. Yu4, Y. Zhao5, L. Zhang6, B. Zhu7, X. Li8, G. Chen9, J. Shi10, R. Zheng11, J. Huang12, S. Yang1, J. Long2, W. Gao3, M. Greco13, G. Hu14, X. Li14 1 Oncology, National Cancer Center/National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China, 2Oncology, Beijing Cancer Hospital, Beijing, China, 3Cancer Center, Jiangsu Province Hospital, Nanjing, China, 4Oncology, Chongqing Cancer Hospital, Chongqing, China, 5Oncology, Henan Cancer Hospital, Zhengzhou, China, 6 Oncology, Yantai Yuhuangding Hospital, Yantai, China, 7Oncology, The Second Affiliated Hospital of Army Medical University, PLA, Chongqing, China, 8Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, 9Oncology, Harbin Medical University Cancer Hospital, Harbin, China, 10Oncology, Shandong Linyi Tumor Hospital, Linyi, China, 11Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China, 12Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China, 13Research and Development, Beta Pharma, Princeton, NJ, USA, 14 Clinical Development, Beta Pharma, Shanghai, China Background: BPI-7711 is a 3rd generation irreversible EGFR-TKI that is selectively against EGFR TKI–sensitizing and T790M resistance mutations. A phase I study is conducted to determine the safety and efficacy of BPI-7711 in patients with advanced or recurrent EGFRmþ/T790Mþ non-small cell lung cancer (NSCLC). Methods: NSCLC patients who had documented disease progression after 1st/2nd generation EGFR-TKI treatment and with EGFRmþ/T790Mþ confirmed by central lab were enrolled in this multicenter trial (NCT03386955) into “3 þ 3” dose escalation or expansion cohorts. BPI-7711 was orally administered at doses of 30300 mg in capsules. Treatment efficacy per RECIST 1.1 was evaluated every 6 weeks from the start of daily treatment. The brain metastases (BM) efficacy was assessed based on radiographical response criteria of Response Assessment in Neuro-Oncology Brain Metastases. Results: As of 15 April 2019, 119 patients were enrolled into 6 dose escalation (30mg300mg) and 5 dose expansion (30240mg) cohorts. BM was present in 44.5% of patients. No DLT was observed and MTD was not reached. For all safety-evaluable patients, the most common treatment related treatment emergent adverse events (TEAEs) (10%) were decreases in neutrophil count (17.6%), white blood cell count (17.6%), platelet count (10.1%), and leukopenia (11.8%). Grade 3 TEAEs occurred
Volume 30 | Supplement 9 | November 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_9/mdz437.001/5638400 by San Francisco State University user on 30 December 2019
Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Clovis; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo / Regeneron / Sanofi; Honoraria (self), Advisory / Consultancy: Debiopharm; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): F Hoffmann-La Roche; Honoraria (self), Advisory / Consultancy: Foundation Medicine; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Illumina; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck Sharp & Dohme; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Honoraria (self), Advisory / Consultancy: Merrimack; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy: Pharma Mar. N. Rizvi: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: BMS; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Lilly; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Regeneron; Advisory / Consultancy: Janssen; Leadership role, Shareholder / Stockholder / Stock options: ARMO BioSciences; Shareholder / Stockholder / Stock options: Gritstone Oncology. All other authors have declared no conflicts of interest.
Annals of Oncology
475O
Overall survival (OS) from the AURA3 phase III study: Osimertinib vs platinum-pemetrexed (plt-pem) in patients (pts) with EGFR T790M advanced non-small cell lung cancer (NSCLC) and progression on a prior EGFR-tyrosine kinase inhibitor (TKI)
Y-L. Wu1, T.S.K. Mok2, J-Y. Han3, M-J. Ahn4, A. Delmonte5, S.S. Ramalingam6, S-W. Kim7, F.A. Shepherd8, J. Laskin9, Y. He10, H. Akamatsu11, W.S.M.E. Theelen12, W-C. Su13, T. John14, M. Sebastian15, H. Mann16, M. Miranda16, G. Laus17, Y. Rukazenkov18, V. Papadimitrakopoulou19 1 Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China, 2Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong, China, 3Center for Lung Cancer, National Cancer Center, Goyang, Republic of Korea, 4Department of Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, 5Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy, 6 Department of Hematology and Medical Oncology, Emory University School of Medicine Winship Cancer Institute, Atlanta, USA, 7Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, 8 Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, ON, Canada, 9 Department of Medicine, BC Cancer Agency, Vancouver, BC, Canada, 10Department of Respiratory Disease, Daping Hospital, Chongqing, China, 11Internal Medicine III, Wakayama Medical University Hospital, Wakayama, Japan, 12Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands, 13Department of Oncology, National Cheng Kung University Hospital, Tainan, Taiwan, 14Department of Medical Oncology, Olivia Newton-John Cancer Research Institute, Melbourne, Australia, 15 Department of Hematology/Medical Oncology, University Hospital Frankfurt, Frankfurt am Main, Germany, 16Oncology R&D, AstraZeneca, Cambridge, UK, 17Global Medicines Development, AstraZeneca, Cambridge, UK, 18Global Medicines Development, AstraZeneca, Cambridge, UK, 19Department of Thoracic Head and Neck Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA Background: In AURA3 (NCT02151981), osimertinib, a 3rd-generation EGFR-TKI, significantly prolonged progressionfree survival (PFS) and improved response rate vs plt-pem in pts with centrally confirmed EGFR T790M advanced NSCLC and progression on a prior EGFR-TKI. Here we report mature OS data. Methods: Adult pts were randomised 2:1 to receive oral osimertinib (80 mg once daily) or intravenous pem (500 mg per m2 of body surface area) þ carboplatin (target area under the curve 5)/cisplatin (75 mg per m2), every 3 weeks, 6 cycles. Treatment beyond progression (RECIST 1.1) was allowed if clinical benefit continued. Pts receiving plt-pem could cross over to osimertinib on disease progression. Asymptomatic CNS metastases were allowed. Primary endpoint was investigator-assessed PFS. OS and safety are reported as secondary endpoints. Data cut-off (DCO): 15 March 2019. Results: In total, 419 pts were randomised (osimertinib, n ¼ 279; plt-pem, n ¼ 140); 99 pts (71%) crossed over to osimertinib from plt-pem. At DCO, 188 pts (67%) in the osimertinib arm vs 93 pts (66%) in the plt-pem arm had died, including 66/99 (67%) crossover pts; median OS 26.8 mo (95% confidence interval [CI] 23.5, 31.5) vs 22.5 mo (95% CI 20.2, 28.8) respectively, hazard ratio (HR) 0.87 (95% CI 0.67, 1.12; p ¼ 0.277); survival rate at 24 mo was 55% vs 43% and at 36 mo was 37% vs 30%. Time to first subsequent treatment showed a large, clinically meaningful numerical advantage towards osimertinib, HR 0.21 (95% CI 0.16, 0.28; p < 0.001); time to second subsequent treatment, HR 0.87 (95% CI 0.69, 1.11; p ¼ 0.263). In both arms, 99% pts had any adverse event (AE). Any AE grade 3 causally related to study treatment was 9% vs 34% for osimertinib and plt-pem respectively. Most common AEs were diarrhoea, 44% (grade 3, 1%), and nausea, 49% (grade 3, 4%), with osimertinib and plt-pem respectively. Conclusions: A numerical advantage in OS was observed for pts receiving osimertinib vs plt-pem, with the majority of pts in the plt-pem arm having crossed over to osimertinib. The safety profile of osimertinib remains consistent with previous findings. Clinical trial identification: NCT02151981. Editorial acknowledgement: Laura Crocker, BMedSci, of iMed Comms, an Ashfield Company, who provided medical writing support funded by AstraZeneca. Legal entity responsible for the study: AstraZeneca.
ix158 | Thoracic tumours, metastatic
Funding: AstraZeneca. Disclosure: Y-L. Wu: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self): Eli Lilly; Honoraria (self): Pfizer; Honoraria (self): MSD; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim. T.S.K. Mok: Honoraria (self): ACEA Pharma, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., LTD., AstraZeneca (before 1/1/19), Bayer, BI, Blueprint Medicines Corporation, BMS, Celgene, CStone Pharmaceuticals, Eli Lilly, Fishawack Facilitate Ltd, Hengrui Therapeutics Inc., Ignyt; Advisory / Consultancy: ACEA Pharma, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., LTD., AstraZeneca (before 1/1/19), Bayer, BI, Blueprint Medicines Corporation, BMS, Celgene, Cirina, CStone Pharmaceuticals, Eli Lilly, Fishawack Facilitate Ltd, geneDecode Co., Ltd. (un; Leadership role: AstraZeneca PLC, Hutchison Chi-Med; Research grant / Funding (institution): AstraZeneca, BMS, Clovis Oncology, MSD, Novartis, Pfizer, Roche, SFJ, XCovery; Shareholder / Stockholder / Stock options: Shareholder: Hutchison Chi-Med, Sanomics Ltd. Stock option: Clearbridge Biomedics (now Biolidics Ltd.), Loxo-Oncology, OrigiMed Co. Ltd., Virtus Medical Group; Full / Part-time employment: The Chinese University of Hong Kong; Officer / Board of Directors: Remunerated: AstraZeneca PLC, Hutchison Chi-Med Non-remunerated: American Society of Clinical Oncology (ASCO) Asian Thoracic Oncology Research Group (ATORG) Chinese Lung Cancer Research Foundation Limited (CLCRF) Chinese Society of Clinical Oncology (CS. J-Y. Han: Honoraria (self): Roche, AstraZeneca, Bristol-Myers Squibb, MSD, Takeda; Advisory / Consultancy: AstraZeneca, Bristol-Myers Squibb, MSD, Takeda, Pfizer, Novartis, Lilly; Research grant / Funding (self): Roche, Pfizer, Ono Pharmaceutical, Takeda. M-J. Ahn: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca, Merck, Sharp & Dohme, Ono Pharmaceutical, Lilly, Roche; Advisory / Consultancy: Alpha Pharmaceutical, Takeda. S.S. Ramalingam: Honoraria (self), Advisory / Consultancy: AstraZeneca, Amgen, Bristol-Myers Squibb, Merck, Roche/Genentech, Loxo, Nektar, Tesaro; Research grant / Funding (institution): AstraZeneca, Amgen, Bristol-Myers Squibb, Merck, Tesaro, Advaxis, Takeda. S-W. Kim: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca. F.A. Shepherd: Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: AstraZeneca. J. Laskin: Research grant / Funding (institution): AstraZeneca, Roche, Boehringer Ingelheim, Pfizer; Honoraria (self): AstraZeneca, Roche, Pfizer. H. Akamatsu: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Honoraria (institution): Chugai; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Pfizer; Honoraria (self), Honoraria (institution): Boehringer Ingelheim. W-C. Su: Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Boehringer Ingelheim. T. John: Advisory / Consultancy: Roche, Bristol-Myers Squibb, Merck, Ignyta, AstraZeneca, Takeda, Boehringer Ingelheim, Pfizer. M. Sebastian: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca, Roche, Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer, Boehringer Ingelheim, Celgene, Takeda, Bristol-Myers Squibb, MSD; Honoraria (self), Advisory / Consultancy: Lilly. H. Mann: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. M. Miranda: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. G. Laus: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. Y. Rukazenkov: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. V. Papadimitrakopoulou: Honoraria (self): F Hoffman-La Roche; Advisory / Consultancy: Nektar Therapeutics, AstraZeneca Pharmaceuticals, Arrys Therapeutics, Merck&Co, LOXO Oncology, Araxes Pharma, F.Hoffman-LaRoche Ltd, Janssen Research Foundation, Bristol-Myers Squibb, Clovis Oncology, Eli Lilly &Co, Novartis Pharmaceuticals Corp. Takeda ; Research grant / Funding (institution): Eli Lilly &Co, Novartis, Merck, AstraZeneca Pharmaceuticals, F Hoffman-La Roche, Nektar Therapeutics, Janssen, Bristol-Myers Squibb, Checkmate, Incyte. All other authors have declared no conflicts of interest.
476O
A phase I study to evaluate safety and efficacy of BPI-7711 in EGFRm1/T790M1 advanced or recurrent NSCLC patients
Y. Shi1, J. Fang2, Y. Shu3, D. Wang4, H. Yu4, Y. Zhao5, L. Zhang6, B. Zhu7, X. Li8, G. Chen9, J. Shi10, R. Zheng11, J. Huang12, S. Yang1, J. Long2, W. Gao3, M. Greco13, G. Hu14, X. Li14 1 Oncology, National Cancer Center/National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China, 2Oncology, Beijing Cancer Hospital, Beijing, China, 3Cancer Center, Jiangsu Province Hospital, Nanjing, China, 4Oncology, Chongqing Cancer Hospital, Chongqing, China, 5Oncology, Henan Cancer Hospital, Zhengzhou, China, 6 Oncology, Yantai Yuhuangding Hospital, Yantai, China, 7Oncology, The Second Affiliated Hospital of Army Medical University, PLA, Chongqing, China, 8Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, 9Oncology, Harbin Medical University Cancer Hospital, Harbin, China, 10Oncology, Shandong Linyi Tumor Hospital, Linyi, China, 11Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China, 12Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China, 13Research and Development, Beta Pharma, Princeton, NJ, USA, 14 Clinical Development, Beta Pharma, Shanghai, China Background: BPI-7711 is a 3rd generation irreversible EGFR-TKI that is selectively against EGFR TKI–sensitizing and T790M resistance mutations. A phase I study is conducted to determine the safety and efficacy of BPI-7711 in patients with advanced or recurrent EGFRmþ/T790Mþ non-small cell lung cancer (NSCLC). Methods: NSCLC patients who had documented disease progression after 1st/2nd generation EGFR-TKI treatment and with EGFRmþ/T790Mþ confirmed by central lab were enrolled in this multicenter trial (NCT03386955) into “3 þ 3” dose escalation or expansion cohorts. BPI-7711 was orally administered at doses of 30300 mg in capsules. Treatment efficacy per RECIST 1.1 was evaluated every 6 weeks from the start of daily treatment. The brain metastases (BM) efficacy was assessed based on radiographical response criteria of Response Assessment in Neuro-Oncology Brain Metastases. Results: As of 15 April 2019, 119 patients were enrolled into 6 dose escalation (30mg300mg) and 5 dose expansion (30240mg) cohorts. BM was present in 44.5% of patients. No DLT was observed and MTD was not reached. For all safety-evaluable patients, the most common treatment related treatment emergent adverse events (TEAEs) (10%) were decreases in neutrophil count (17.6%), white blood cell count (17.6%), platelet count (10.1%), and leukopenia (11.8%). Grade 3 TEAEs occurred
Volume 30 | Supplement 9 | November 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_9/mdz437.001/5638400 by San Francisco State University user on 30 December 2019
Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Clovis; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo / Regeneron / Sanofi; Honoraria (self), Advisory / Consultancy: Debiopharm; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): F Hoffmann-La Roche; Honoraria (self), Advisory / Consultancy: Foundation Medicine; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Illumina; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck Sharp & Dohme; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Honoraria (self), Advisory / Consultancy: Merrimack; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy: Pharma Mar. N. Rizvi: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: BMS; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Lilly; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Regeneron; Advisory / Consultancy: Janssen; Leadership role, Shareholder / Stockholder / Stock options: ARMO BioSciences; Shareholder / Stockholder / Stock options: Gritstone Oncology. All other authors have declared no conflicts of interest.
Annals of Oncology