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Displaying One Session

Channel 1 Proffered Paper session
Date
19.09.2020
Time
18:30 - 20:10
Room
Channel 1
Chairs
  • Solange Peters (Lausanne, Switzerland)
  • John B. Haanen (Amsterdam, Netherlands)
Presidential Symposium I Proffered Paper session

LBA1 - Osimertinib adjuvant therapy in patients (pts) with resected EGFR mutated (EGFRm) NSCLC (ADAURA): Central nervous system (CNS) disease recurrence

Presentation Number
LBA1
Lecture Time
18:30 - 18:42
Speakers
  • Masahiro Tsuboi (Kashiwa, Chiba, Japan)
Room
Channel 1
Date
19.09.2020
Time
18:30 - 20:10

Abstract

Background

CNS relapse is common in NSCLC, and is a poor prognostic factor. In the resected EGFRm NSCLC setting, the impact of treatment on sites of recurrence, including the CNS, is a key consideration. Osimertinib is a 3rd-generation EGFR-TKI with demonstrated efficacy in NSCLC CNS metastases. In ADAURA, osimertinib demonstrated a highly statistically significant and clinically meaningful improvement in disease-free survival vs placebo (PBO; DFS, hazard ratio [HR]: 0.20 [99.12% CI 0.14, 0.30; p<0.001) in resected stage IB–IIIA EGFRm (ex19del/L858R) NSCLC (Ph III ADAURA; NCT02511106). We report an exploratory analysis of recurrence patterns.

Methods

Pts with resected stage IB–IIIA EGFRm NSCLC, with/without adjuvant chemotherapy, were randomised 1:1 to receive osimertinib 80 mg once-daily or PBO until recurrence/discontinuation/3 years. Patterns of recurrence and CNS DFS (time to CNS recurrence/death) were exploratory endpoints. An MRI/CT brain scan was mandated at baseline either before surgery or upon enrolment, but was not required in absence of symptoms. Recurrence was categorised as local/regional and/or distant, with sites of relapse recorded. Data cutoff: 17/01/20.

Results

Overall, 682 pts were randomised (osimertinib: 339; PBO: 343). Pts treated with osimertinib had fewer recurrence events vs PBO (Table); 45 pts had CNS DFS events (osimertinib: 6; PBO: 39; median follow-up 22 months [mo]). Conditional probability of CNS recurrence at 12 mo (95% CI): <1% (0%, 2%) with osimertinib vs 7% (4%, 10%) with PBO. Median CNS DFS: not reached (95% CI 39.0 mo, not calculable [NC]) with osimertinib vs 48.2 (NC, NC) mo with PBO. CNS DFS HR: 0.18 (95% CI 0.10, 0.33); p<0.0001.

Osimertinib n=339 PBO n=343
CNS DFS events, pts (%): 6 (2) 39 (11)
CNS recurrence 4 (1) 33 (10)
Death* 2 (1) 6 (2)
DFS events, pts (%): 37 (11) 159 (46)
Disease recurrence 37 (11) 157 (46)
Non-CNS recurrence 33 (10) 123 (36)
CNS recurrence 4 (1) 33 (10)
Disease recurrence with missing location 0 1 (0)
Death 0 2 (1)

*Death in absence of CNS disease recurrence, or death within two visits of baseline where the patient has no evaluable assessments or no baseline data. †Death in the absence of disease recurrence (any site), or death within two visits of baseline where the patient has no evaluable assessments or no baseline data.

Conclusions

There was a clinically meaningful improvement in CNS DFS with osimertinib: 82% reduction in risk of CNS disease recurrence or death. Results support that osimertinib reduces risk of CNS recurrence in the resected EGFRm NSCLC setting.

Clinical trial identification

NCT02511106.

Editorial acknowledgement

Natasha Learmond, BSC, of Ashfield Healthcare Communications, Macclesfield, UK, part of UDG Healthcare plc for medical writing support that was funded by AstraZeneca in accordance with Good Publications Practice (GPP3) guidelines.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

M. Tsuboi: Honoraria (self): Johnson & Johnson Japan; Honoraria (self), Research grant/Funding (institution): AstraZeneca KK; Honoraria (self): Eli Lilly Japan; Honoraria (self), Research grant/Funding (institution): Boehringer-Ingelheim Japan; Honoraria (self): Chugai Pharmaceutical Co., Ltd; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self): Bristol-Myers Squibb KK; Honoraria (self): Teijin Pharma; Honoraria (self): Taiho Pharma; Honoraria (self): Medtronic Japan; Honoraria (self): Ono Pharmaceutical Co., Ltd. Y-L. Wu: Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Speaker Bureau/Expert testimony, Research grant/Funding (institution): BMS; Speaker Bureau/Expert testimony: Eli Lilly; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Speaker Bureau/Expert testimony: Sanofi; Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche. T. John: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Shareholder/Stockholder/Stock options: AstraZeneca; Honoraria (institution): Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: BMS; Advisory/Consultancy: Merck; Advisory/Consultancy: Ignyta; Advisory/Consultancy: Takeda; Advisory/Consultancy: MSD; Advisory/Consultancy: Specialised Therapeutics; Advisory/Consultancy: Pfizer. C. Grohe: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD. M. Majem: Honoraria (self), Research grant/Funding (self): BMS; Honoraria (self): MSD; Honoraria (self): Boehringer Ingelheim; Honoraria (self): AstraZeneca; Honoraria (self): Roche; Honoraria (self): Kyowa Kyrin; Honoraria (self): Pierre Fabre; Honoraria (self): Takeda; Honoraria (self): Bayer. J.W. Goldman: Speaker Bureau/Expert testimony: Merck; Honoraria (self), Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): AbbVie; Research grant/Funding (self): Merck; Research grant/Funding (self): BMS. S-W. Kim: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca. T. Kato: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): AbbVie; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Chugai; Advisory/Consultancy, Research grant/Funding (self): Eli Lilly; Advisory/Consultancy, Research grant/Funding (self): Merck Biopharma; Advisory/Consultancy, Research grant/Funding (self): MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Ono; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Daiichi-Sankyo; Advisory/Consultancy: Nippon Kayaku; Advisory/Consultancy: Nitto Denko; Advisory/Consultancy: Sumitomo Dainippon; Advisory/Consultancy: Takeda; Speaker Bureau/Expert testimony, Research grant/Funding (self): Bristol Myers Squibb; Research grant/Funding (self): Novartis; Research grant/Funding (self): Taiho; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Speaker Bureau/Expert testimony: F.Hoffman-La Rohe; Speaker Bureau/Expert testimony: Shionogi. F. de Marinis: Advisory/Consultancy: Roche; Advisory/Consultancy: BMS; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: MSD; Advisory/Consultancy: Pfizer. M. Domine: Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche. F.A. Shepherd: Honoraria (self), Shareholder/Stockholder/Stock options: AstraZeneca. C. Yan, A. Atasoy: Full/Part-time employment: AstraZeneca. R. Herbst: Honoraria (self): AbbVie; Honoraria (self): Armo Biosciences; Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self): Biodesix; Honoraria (self): Bolt Biotherapeutics; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (self): Eli Lilly; Honoraria (self): Cybrexa; Honoraria (self): EMD Serrano; Honoraria (self), Research grant/Funding (self): Genentech/Roche; Honoraria (self): Genmab; Honoraria (self): Halozyme; Honoraria (self): Heat Biologics; Honoraria (self): IMAB Biopharma; Honoraria (self): Immunocore; Honoraria (self): Infinity Pharmaceuticals; Honoraria (self): Loxo Oncology; Honoraria (self), Research grant/Funding (self): Merck; Honoraria (self): Mirati Therapeutics; Honoraria (self): Nektar; Honoraria (self): Neon Therapeutics; Honoraria (self): NextCure; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Sanofi; Honoraria (self): Seattle Genetics; Honoraria (self): Shire PLC; Honoraria (self): Spectrum Pharmaceuticals; Honoraria (self): Symphogen; Honoraria (self): Takeda, Tesaro, Tocagen, WindMIL Therapeutics; Officer/Board of Directors: Junshi Pharmaceuticals. All other authors have declared no conflicts of interest.

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Presidential Symposium I Proffered Paper session

Invited Discussant LBA1

Lecture Time
18:42 - 18:52
Speakers
  • Johan F. Vansteenkiste (Leuven, Belgium)
Room
Channel 1
Date
19.09.2020
Time
18:30 - 20:10
Presidential Symposium I Proffered Paper session

Q&A and live discussion

Lecture Time
18:52 - 19:02
Speakers
  • Solange Peters (Lausanne, Switzerland)
Room
Channel 1
Date
19.09.2020
Time
18:30 - 20:10
Presidential Symposium I Proffered Paper session

LBA2 - Lorlatinib vs crizotinib in the first-line treatment of patients (pts) with advanced ALK-positive non-small cell lung cancer (NSCLC): Results of the phase III CROWN study

Presentation Number
LBA2
Lecture Time
19:02 - 19:14
Speakers
  • Benjamin Solomon (Melbourne, VIC, Australia)
Room
Channel 1
Date
19.09.2020
Time
18:30 - 20:10

Abstract

Background

Lorlatinib, a 3rd generation ALK tyrosine kinase inhibitor has shown overall and intracranial (IC) activity in advanced ALK+ NSCLC. We report interim data from an open label randomized, multicenter, phase III study of lorlatinib vs crizotinib in pts with untreated ALK+ NSCLC (NCT03052608).

Methods

Untreated pts with ALK+ Stage IIIB/IV NSCLC (104 study sites; 23 countries) were randomized 1:1 to oral lorlatinib (100 mg QD) or crizotinib (250 mg BID); stratified by presence of CNS metastases and ethnicity. The primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR). PFS by investigator (INV), objective response (OR) and IC-OR by BICR, duration of response (DR), IC-DR, overall survival (OS) and safety were secondary endpoints. This planned interim analysis was conducted at 72% of 177 expected PFS events.

Results

Of 296 pts randomized, 291 received study treatment. At data cutoff (20 March 2020), median follow-up for PFS by BICR was 18.3 months (95% CI 16.4, 20.1) for lorlatinib (n=149) and 14.8 months (95% CI 12.8, 18.4) for crizotinib (n=147). PFS by BICR was significantly prolonged with lorlatinib vs crizotinib (HR 0.28; 95% CI 0.191, 0.413; stratified 1-sided p<0.001). Lorlatinib median PFS was NE (not estimable) (95% CI NE, NE) vs crizotinib 9.3 months (95% CI 7.6, 11.1). PFS by INV, OR and IC-OR by BICR were improved with lorlatinib vs crizotinib (Table). Grade 3–4 adverse events (AE)/AEs leading to treatment discontinuation: 72.5%/6.7% for lorlatinib; 55.6%/9.2% for crizotinib. The majority of Grade 3–4 AEs for lorlatinib were laboratory abnormalities, the most common of which were lipid abnormalities.

Lorlatinib (N=149) Crizotinib (N=147)
12-month PFS rate by BICR (%) 78.1 38.7
(95% CI) (70.3, 84.0) (29.8, 47.5)
PFS by INV
Median PFS, months (95% CI) NE (NE, NE) 9.1 (7.4, 10.9)
HR (95% CI) 0.21 (0.144, 0.307)
BOR by BICR, n (%)
CR 4 (3) 0 (0)
PR 109 (73) 85 (58)
SD 19 (13) 41 (28)
Non-CR/Non-PD 3 (2) 3 (2)
Median DR, months (95% CI) NE (NE, NE) 11.0 (9.0, 12.9)
IC BOR by BICR for pts with measurable brain metastases, n (%)
Patients, n 17 13
CR 12 (71) 1 (8)
PR 2 (12) 2 (15)
SD 1 (6) 5 (39)
IC-DR*, range in months 3.9–31.4 5.4–11.1

BOR, best overall response; CR, complete response; PR, partial response; SD, stable disease, PD, progressive disease. *censored in 86% and 33% of patients, respectively.

Conclusions

Lorlatinib resulted in a statistically significant and clinically meaningful improvement in PFS vs crizotinib and should be considered a new first-line treatment option for pts with ALK+ NSCLC.

Clinical trial identification

NCT03052608.

Editorial acknowledgement

Medical writing support was provided by Paul O’Neill, PhD, of CMC AFFINITY, McCann Health Medical Communications, and was funded by Pfizer Inc.

Legal entity responsible for the study

Pfizer Inc.

Funding

Pfizer Inc.

Disclosure

B. Solomon: Advisory/Consultancy, Ad board: Pfizer; Advisory/Consultancy, Ad board: Novartis; Advisory/Consultancy, Ad board: Roche-Genentech; Advisory/Consultancy, Ad board: AstraZeneca; Advisory/Consultancy, Ad board: Bristol-Myers Squibb; Advisory/Consultancy, Ad board: Merck; Advisory/Consultancy, Ad board: Amgen; Advisory/Consultancy, Ad board: Gritstone Oncology. T.M. Bauer: Full/Part-time employment: Tennessee Oncology; Advisory/Consultancy: Guardant Health; Advisory/Consultancy: Loxo; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Blueprint Medicines; Advisory/Consultancy: Foundation Medicine; Advisory/Consultancy: Ignyta; Advisory/Consultancy: Moderna Therapeutics; Advisory/Consultancy: Pfizer; Speaker Bureau/Expert testimony: Bayer; Research grant/Funding (institution): Daiichi Sankyo; Medpacto, Inc.; Incyte; Mirati Therapeutics; MedImmune; AbbVie; AstraZeneca; Leap Therapeutics; MabVax, Stemline Therapeutics; Merck; Lilly; GlaxoSmithKline; Novartis; Pfizer; Genentech/Roche; Deciphera; Merrimack; Immunogen; Millennium; Travel/Accommodation/Expenses, Travel, accommodations, expenses: Astellas Pharma; AstraZeneca; Celgene; Clovis Oncology; EMD Serono; Genentech; Lilly; Merck; Novartis; Pharmacyclics; Sysmex; Pfizer; Advisory/Consultancy, Payment to institution for consulting services performed by Dr. Bauer: Leap Therapeutics; Advisory/Consultancy, Travel/Accommodation/Expenses, Reimbursement of expenses; payment to institution for consulting services performed by Dr. Bauer: Ignyta; Moderna Therapeutics; Pfizer; Loxo; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: Guardant Health; Advisory/Consultancy: Exelesis; Blueprint Medicines; Foundation Medicine; Research grant/Funding (institution): Ignyta; Calithera Biosciences; Kolltan Pharmaceuticals; Principa Biopharma; Peleton; Immunocore; Roche; Aileron Therapeutics; Bristol-Myers Squibb; Amgen; Moderna Therapeutics; Sanofi; Boehringer Ingelheim; Astellas Pharma; Five Prime Therapeutics; Research grant/Funding (institution): Jacobio; Top Alliance BioScience; Loxo; Janssen; Clovis Oncology; Takeda; Karyopharm Therapeutics; Onyx; Phosplatin Therapeutics; Foundation Medicine; Armo BioSciences. E. Felip: Advisory/Consultancy, Advisory Boards: AbbVie; AstraZeneca; Blue Print Medicines; Boehringer Ingelheim; Bristol-Myers Squibb, GSK; Eli Lilly; Guardant Health; Janssen; Medscape; Merck KGaA; Merck Sharp & Dohme; Novartis; Pfizer; Prime Oncology; Roche; Samsung; Springer; Takeda; Touchime; Speaker Bureau/Expert testimony, Board: Grífols Independent Member; Research grant/Funding (institution), Research Funding. Fundación Merck Salud; Grant For Oncology Innovation (Goi) EMD Serono. Y. Goto: Advisory/Consultancy: Eli Lilly; Chugai; Taiho Pharmaceutical; Boehringer Ingelheim; Pfizer; Novartis; AstraZeneca; GlaxoSmithKline; MSD; Guardant Health; Daiichi Sankyo; Kyorin; Chugai; Speaker Bureau/Expert testimony: Illumina; AstraZeneca; Eli Lilly; Chugai; Taiho Pharmaceutical; Boehringer Ingelheim; Ono Pharmaceutical; Bristol-Myers Squibb; Pfizer; MSD; Shionogi Pharma; Novartis; Research grant/Funding (institution): AbbVie; Eli Lilly; Taiho Pharmaceutical; Bristol Myers Squibb; Ono Pharmaceutical; Daiichi Sankyo; Pfizer; Novartis; Kyorin; Chugai; Guardant Health; Daiichi-Sankyo. G. Liu: Advisory/Consultancy, Advisory board: Pfizer; Novartis; Merck; BMS; Roche; Advisory/Consultancy, Leadership role, Research grant/Funding (institution), Advisory board; educational rounds; research grants to institution: Takeda; AstraZeneca; Leadership role, Educational rounds: EMD Serono . J. Mazieres: Advisory/Consultancy: Roche, AstraZeneca, MSD, BMS, Pfizer, Hengrui, Daiichi, Boehringer, Pierre Fabre; Research grant/Funding (institution): Roche, AstraZeneca, Pierre Fabre. D-W. Kim: Research grant/Funding (institution): Alpha Biopharma, Astrazeneca/MedImmune, Boehringer-Ingelheim, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, and Yuhan; Travel/Accommodation/Expenses: Amgen, Daiichi-Sankyo. T. Mok: Research grant/Funding (institution): AstraZeneca, BMS, Clovis Oncology, G1 Therapeutics, MSD, Merck Serono, Novartis, Pfizer, Roche, SFJ, Takeda, XCovery ; Speaker Bureau/Expert testimony, Speaker's fees: ACEA Pharma; Alpha Biopharma Co., Ltd.; Amgen; Amoy Diagnostics Co., Ltd.; AstraZeneca (before 1/1/19); BI; BMS; Eli Lilly; InMed Medical Communication; MSD; Novartis; Pfizer; PrIME Oncology; Roche/Genentech; Taiho; Takeda Oncology; Honoraria (self), Honoraria/Honorarium Received (for consultation services): AbbVie Inc.; ACEA Pharma (Monthly since Aug 2018); Alpha Biopharma Co., Ltd.; Amgen; Amoy Diagnostics Co., Ltd.; AstraZeneca (before 1/1/19); Bayer; BI; Blueprint Medicines Corporation; BMS; Celgene; CStone Pharmaceuticals; Daiichi Sankyo; Eli Lilly; Honoraria (institution), Medical education/CME activities: Medscape/WebMD; Honoraria (institution), Independent medical education: PeerVoice; Honoraria (institution), Medical education: Prime Oncology; Shareholder/Stockholder/Stock options, Shareholder: Hutchison Chi-Med; Sanomics Ltd.; Shareholder/Stockholder/Stock options, Stock: Clearbridge Biomedics (now Biolidics Ltd.); Loxo-Oncology; OrigiMed Co. Ltd.; Virtus Medical Group; Advisory/Consultancy, Advisory Board: AbbVie Inc.; ACEA Pharma; Amgen; AstraZeneca; Bayer; Blueprint Medicines Corporation; Boehringer Ingelheim; Bristol-Myers Squibb; Celgene; Cirina; CStone Pharmaceuticals; Daiichi Sankyo; Eli Lilly; Fishawack Facilitate Ltd.; G1 Therapeutics, Inc.; Leadership role, Board of Directors/Leadership roles (remunerated): AstraZeneca PLC; Hutchison Chi-Med; Leadership role, Board of Directors/Leadership roles (non-remunerated): American Society of Clinical Oncology (ASCO); Asian Thoracic Oncology Research Group (ATORG); Chinese Lung Cancer Research Foundation Limited (CLCRF); Honoraria (self), Honoraria/Honorarium received (for consultation services): Fishawack Facilitate Ltd.; Hengrui Therapeutics Inc; Ignyta, Inc.; Incyte Corporation; InMed Medical Communication; IQVIA; Janssen; Loxo-Oncology; Merck Serono; MSD; Honoraria (self), Honoraria/Honorarium Received (for consultation services): MoreHealth; Novartis; OncoGenex Pharmaceuticals, Inc.; OrigiMed; PeerVoice; Pfizer; PrIME Oncology; Roche/Genentech; Sanofi-Aventis R&D; SFJ Pharmaceutical Ltd.; Honoraria (self), Honoraria/Honorarium Received (for consultation services): Takeda Pharmaceuticals HK Ltd.; Vertex Pharmaceuticals; Yuhan Corporation; Advisory/Consultancy, Advisory Board: geneDecode Co., Ltd. (uncompensated); Hengrui Therapeutics Inc.; Hutchison Chi-Med; Ignyta, Inc.; Incyte Corporation; IQVIA; Janssen; Loxo-Oncology; Lunit, Inc.; Merck Serono; Merck Sharp & Dohme; Advisory/Consultancy, Advisory Board: Novartis; OncoGenex Technologies Inc.; OrigiMed; Pfizer; Roche/Genentech; Sanofi-Aventis R&D; SFJ Pharmaceutical; Takeda Oncology; Vertex Pharmaceuticals; Virtus Medical Group; Yuhan Corporation; Leadership role, Board of Directors/Leadership roles (non-remunerated): Chinese Society of Clinical Oncology (CSCO); Hong Kong Cancer Fund (HKCF); Hong Kong Cancer Therapy Society (HKCTS); International Association for the Study of Lung Cancer (IASLC) – term ended on 30/4/19; St. Stephen’s College & Prep. School. A. Polli: Full/Part-time employment, Employee: Pfizer Inc. H. Thurm: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer Inc. A.M. Calella: Full/Part-time employment: Pfizer Inc. G. Peltz: Full/Part-time employment: Pfizer Inc. A. Shaw: Honoraria (institution): Pfizer, Novartis, Genentech/Roche, Ariad/Takeda, Ignyta, Loxo, Bayer, Chugai, Blueprint Medicines, KSQ Therapeutics, Daiichi Sankyo, EMD Serono, Taiho Pharmaceutical, TP Therapeutics, Servier, Syros, Foundation Medicine, Guardant, Natera, Achilles, Archer; Travel/Accommodation/Expenses: Pfizer and Genentech; Full/Part-time employment: Novartis; Research grant/Funding (institution): Pfizer, Novartis, Roche/Genentech, Ariad, Ignyta, TP Therapeutics. All other authors have declared no conflicts of interest.

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Presidential Symposium I Proffered Paper session

Invited Discussant LBA2

Lecture Time
19:14 - 19:24
Speakers
  • Christine Lovly (Nashville, TN, United States of America)
Room
Channel 1
Date
19.09.2020
Time
18:30 - 20:10
Presidential Symposium I Proffered Paper session

Q&A and live discussion

Lecture Time
19:24 - 19:34
Speakers
  • Solange Peters (Lausanne, Switzerland)
Room
Channel 1
Date
19.09.2020
Time
18:30 - 20:10
Presidential Symposium I Proffered Paper session

696O_PR - Nivolumab + cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: First results from the randomized phase III CheckMate 9ER trial

Presentation Number
696O_PR
Lecture Time
19:34 - 19:46
Speakers
  • Toni K. Choueiri (Boston, United States of America)
Room
Channel 1
Date
19.09.2020
Time
18:30 - 20:10

Abstract

Background

Results from the phase 3 CheckMate 9ER trial evaluating the checkpoint inhibitor (CPI) nivolumab (N) plus the tyrosine kinase inhibitor (TKI) cabozantinib (C) v sunitinib (S) for first-line (1L) treatment of advanced clear cell renal cell carcinoma (aRCC) are reported. As monotherapies, N and C have demonstrated efficacy and a manageable safety profile in aRCC. C has immunomodulatory properties that may counteract tumor-induced immunosuppression, providing a rationale for combining N+C.

Methods

Patients (pts) were randomized 1:1 (stratified by IMDC risk score, tumor PD-L1 expression, region) to N 240 mg flat dose IV Q2W + C 40 mg PO QD v S 50 mg PO for 4 wk (6-wk cycles) until disease progression or unacceptable toxicity (max N treatment, 2 y). Primary endpoint: progression-free survival (PFS; a ¼ 0.05 final) by blinded independent central review (BICR). Secondary endpoints (hierarchical testing): overall survival (OS; a ¼ 0.011 first interim analysis), objective response rate (ORR; a ¼ 0.05 final) by BICR, and safety.

Results

A total of 651 pts (22.6% favorable risk, 57.6% intermediate risk, 19.7% poor risk; 24.9% PD-L1 _1%) were randomized to N+C (n ¼ 323) v S (n ¼ 328). With 18.1 mo median (10.6 mo minimum) study follow-up, all 3 efficacy endpoints were met. N+C significantly improved PFS (HR 0.51 [95% CI 0.41e0.64], P < 0.0001; median, 16.6 v 8.3 mo) and OS (HR 0.60 [98.89% CI 0.40e0.89]; P ¼ 0.0010; medians not reached) v S, and results were consistent across prespecified IMDC risk and PD-L1 subgroups. ORR (95% CI) was significantly higher with N+C v S (55.7% [50.1e61.2] v 27.1% [22.4e32.3]; P < 0.0001), and 8.0% v 4.6% of pts achieved complete response. Median duration of response was 20.2 v 11.5 mo for N+C v S. Any-grade TRAEs occurred in 96.6% v 93.1% of pts treated with N+C v S (60.6% v 50.9% grade _3). One treatment-related death occurred with N+C v 2 with S. TRAEs led to discontinuation of S in 8.8%, N or C in 15.3%, N+C in 3.1%, N only in 5.6%, and C only in 6.6% of pts.

Conclusions

N+C demonstrated superior PFS, OS, and ORR v S in 1L aRCC. The safety profile of this combination was manageable and consistent with the known singleagent AE profiles of N and C. These results support N+C as a new CPI+TKI option for aRCC pts.

Clinical trial identification

NCT03141177.

Editorial acknowledgement

Professional medical writing assistance was provided by Jen Tyson, PhD, of Parexel, funded by Bristol-Myers Squibb Company.

Legal entity responsible for the study

Bristol-Myers Squibb Company.

Funding

Bristol-Myers Squibb Company (Princeton, NJ), Ono Pharmaceutical Company Ltd. (Osaka, Japan), and Exelixis Inc. (Alameda, CA).

Disclosure

T.K. Choueiri: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Manuscript preparation, Clinical trials grants: BMS; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Manuscript preparation, Clinical trials grants: Exelixis; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses, Manuscript preparation, Clinical trials grants: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Manuscript preparation, Clinical trials grants: Merck; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Manuscript preparation, Clinical trials grants: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Manuscript preparation, Clinical trials grants: Lilly; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Manuscript preparation, Clinical trials grants: Eisai; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Manuscript preparation, Clinical trials grants: Novartis; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Manuscript preparation, Clinical trials grants: GSK; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Manuscript preparation, Clinical trials grants: EMD Serono; Shareholder/Stockholder/Stock options: Pionyr; Shareholder/Stockholder/Stock options: Tempest. T. Powles: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Exelixis; Honoraria (self), Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy: Ipsen; Honoraria (self), Advisory/Consultancy: Merck/MSD; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Roche. M.T. Bourlon: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses, Slide reviews: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Janssen. J.J. Hsieh: Research grant/Funding (self), Sponsered Clinical trial: BMS; Advisory/Consultancy, Research grant/Funding (self), Sponsored Clinical trial: Eisai; Research grant/Funding (self), Sponsored Clinical trial: Calithera; Research grant/Funding (self), Investigator initiated trial and correlate studies: AstraZeneca. U. Basso: Speaker Bureau/Expert testimony, Research grant/Funding (self), Carry out activities of the study: BMS. C. Suarez: Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche/Genentech; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Astellas; Honoraria (self), Advisory/Consultancy: AtraZeneca; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Eusa; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Ipsen; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Sanofi-Aventis; Honoraria (self), Advisory/Consultancy: Merck Sharp & Dohme Corp. C.H. Barrios: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer-Ingelheim; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche/Genentech; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Eisai; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstellasPharma; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Covance; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): PharmMar. D. Pook: Advisory/Consultancy, Commercial Study Finding: BMS; Advisory/Consultancy, Research grant/Funding (self): Pfizer; Research grant/Funding (self): Ipsen. Y. Tomita: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Ono pharmacetical; Honoraria (self): BMS; Honoraria (self), Research grant/Funding (self): Pfizer; Research grant/Funding (institution): Takeda. B. Escudier: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Ipsen; Honoraria (self), Advisory/Consultancy: Eusa Pharma; Honoraria (self): Roche/Genentech. J. Zhang: Shareholder/Stockholder/Stock options, Full/Part-time employment: BMS. B. Simsek: Shareholder/Stockholder/Stock options, Full/Part-time employment: BMS. R.J. Motzer: Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy: Merck; Advisory/Consultancy: Incyte; Advisory/Consultancy: Lilly. All other authors have declared no conflicts of interest.

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Presidential Symposium I Proffered Paper session

Invited Discussant 696O_PR

Lecture Time
19:46 - 19:56
Speakers
  • Camillo Guglielmo Porta (Pavia, Italy)
Room
Channel 1
Date
19.09.2020
Time
18:30 - 20:10
Presidential Symposium I Proffered Paper session

Q&A and live discussion

Lecture Time
19:56 - 20:06
Speakers
  • Solange Peters (Lausanne, Switzerland)
Room
Channel 1
Date
19.09.2020
Time
18:30 - 20:10