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Presidential symposium
Date
Sat, 18.09.2021
Time
15:05 - 16:35
Location
Channel 1
Chairs
  • Andres Cervantes (Valencia, Valencia, Spain)
  • Solange Peters (Lausanne, Switzerland)
Presidential symposium

LBA1 - Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (Pts) with HER2+ metastatic breast cancer (mBC): Results of the randomized phase III DESTINY-Breast03 study

Presentation Number
LBA1
Speakers
  • Javier Cortés (Madrid, Spain)
Lecture Time
15:05 - 15:20
Session Name
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Sat, 18.09.2021
Time
15:05 - 16:35

Abstract

Background

T-DXd is a HER2-targeting antibody–drug conjugate approved for pts with advanced HER2+ mBC based on the results from DESTINY-Breast01 (NCT03248492). This is the first report of DESTINY-Breast03 (NCT03529110), a multicenter, open-label, randomized phase 3 study comparing the efficacy and safety of T-DXd vs T-DM1 in pts with HER2+ mBC previously treated with trastuzumab and taxane. This is the first reported randomized study of T-DXd in BC.

Methods

Pts were randomized 1:1. The primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR). Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response, PFS by investigator, and safety.

Results

As of May 21, 2021, 524 pts were randomized. Median age was 54 years (range, 20-83). The hazard ratio (HR) for PFS was 0.2840 (P = 7.8 x 10-22); median PFS not reached for T-DXd vs 6.8 mo for T-DM1. The estimated 12-month OS event rates were 94.1% (95% CI, 90.3-96.4) for T-DXd and 85.9% (95% CI, 80.9-89.7) for T-DM1; HR: 0.5546 (95% CI, 0.3587-0.8576; P = 0.007172 did not cross pre-specified boundary for significance). Median treatment duration was 14.3 mo (range, 0.7-29.8) with T-DXd vs 6.9 mo (range, 0.7-25.1) with T-DM1; similar rates of TEAEs were observed. No drug-related deaths occurred in either arm. Adjudicated drug-related interstitial lung disease (ILD) occurred in 10.5% of pts with T-DXd (most [9.7%] grade 1/2; 0 grade 4/5) vs 1.9% with T-DM1 (all grade 1/2).

Summary of results

T-DXd N = 261 T-DM1 N = 263
PFS by BICR HR 0.2840 (95% CI, 0.2165-0.3727); P = 7.8X10 -22,a
Median PFS, mo (95% CI) Not reached (18.5-NE) 6.8 (5.6-8.2)
PFS by Investigator HR 0.2649 (95% CI, 0.2011-0.3489); P = 6.5X10 -24,a
Median PFS, mo (95% CI) 25.1 (22.1-NE) 7.2 (6.8-8.3)
Confirmed ORR, % (95% CI) b 79.1 (74.3-84.4) 34.2 (28.5-40.3)
P < 0.0001a
Safety, n (%) T-DXd N = 257 c T-DM1 N = 261 c
Any grade TEAEs 256 (99.6) 249 (95.4)
Grade ≥3 134 (52.1) 126 (48.3)
Serious TEAEs 49 (19.1) 47 (18.0)

aTwo-sided. bBy BICR. cOf 524 pts, 257 and 261 received ³1 dose of T-DXd and T-DM1, respectively.

Conclusions

T-DXd demonstrated a highly statistically significant and clinically meaningful improvement in PFS vs T-DM1 in pts previously treated with trastuzumab and taxane for HER2+ mBC. These data confirm that T-DXd is tolerable with manageable toxicity and a significant improvement in ILD profile vs studies performed in more heavily pretreated pts. This study will lead to a paradigm shift in the treatment of HER2+ mBC.

Clinical trial identification

NCT03529110.

Editorial acknowledgement

Under the guidance of authors, assistance in medical writing and editorial support was provided by Irene Park, PhD, and Alya Raphael, PhD, of ApotheCom, and was funded by Daiichi Sankyo, Inc.

Legal entity responsible for the study

Daiichi Sankyo, Inc., and AstraZeneca.

Funding

Daiichi Sankyo, Inc., and AstraZeneca.

Disclosure

J. Cortés: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Cellestia; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Biothera; Financial Interests, Personal, Advisory Board: Merus; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Erytech; Financial Interests, Personal, Advisory Board: Athenex; Financial Interests, Personal, Advisory Board: Polyphor; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Advisory Board: Merck Sharp& Dohme; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: LEUKO; Financial Interests, Personal, Advisory Board: Bioasis; Financial Interests, Personal, Advisory Board: Clovis oncology; Financial Interests, Personal, Advisory Board: Boehringer; Financial Interests, Personal, Advisory Board: Kyowa Kyrin; Financial Interests, Personal, Advisory Board: 4D Pharma PLC; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Celgene; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Samsung Bioepis; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: MedSIR; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Ariad Pharmaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Baxalta GMBH/Servier Affaires,; Financial Interests, Institutional, Research Grant: Bayer healthcare; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Guardanth health,; Financial Interests, Institutional, Research Grant: Merck Sharp&Dohme,; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Piqur Therapeutics; Financial Interests, Institutional, Research Grant: Puma B; Financial Interests, Institutional, Research Grant: Queen Mary University of London; Other, Travel cost and expenses: Roche; Other, Travel cost and expenses: Novartis; Other, Travel cost and expenses: Eisai; Other, Travel cost and expenses: Daiichi Sankyo. S. Kim: Financial Interests, Personal, Advisory Role, Advisory/Consultancy: Novartis, AstraZeneca, Lilly, Dae Hwa Pharmacuetical Co. Ltd, ISU Abxis, Daiichi Sankyo; Other, Personal, Leadership Role: ESMO Breast 2021-2022 Co-chair; Financial Interests, Personal, Stocks/Shares: Genepeaks, Neogene TC; Financial Interests, Institutional, Research Grant: Novartis, Sanofi-Aventis, and DongKook Pharm Co. W. Chung: Financial Interests, Personal, Advisory Role, Advisory/Consultancy: Novartis, AstraZeneca, Pfizer, Amgen, Eli Lilly, MSD, and Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau, Speaker Bureau/Expert Testimony: Novartis, Roche, AstraZeneca, Pfizer, Amgen, Kyowa Kirin, Foundation Medicine, Chugai Pharma, Takeda, Eli Lilly, and Sanofi. S. Im: Financial Interests, Personal, Advisory Role, Advisory/Consultancy: AstraZeneca, Amgen, Eisai, Hanmi, Novartis, Pfizer, Roche, Eli-Lilly, MSD, GSK, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: AstraZeneca, Eisai, Pfizer, Roche, Daiichi Sankyo, Dae Woong. Y.H. Park: Non-Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant, Contracted research: AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: AstraZeneca; Non-Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Research Grant, Contracted research: Pfizer; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Pfizer; Non-Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Research Grant, Contracted research: Roche; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Roche; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Daiichi Sankyo; Non-Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Speaker fee: Novartis; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Novartis; Non-Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Institutional, Research Grant, Contracted research: Merck; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Merck; Non-Financial Interests, Personal, Other, Medical writing support for this abstract, furnished by Daniel Clyde, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. V. Petry: Financial Interests, Personal, Advisory Role, Advisory/Consultancy: Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau, Speaker's Bureau/Expert Testimony: Novartis; Financial Interests, Personal, Speaker’s Bureau, Speaker's Bureau/Expert Testimony: Pfizer; Financial Interests, Personal, Other, Travel expenses, including accommodations: Roche; Financial Interests, Personal, Other, Travel expenses, including accommodations: Lilly; Financial Interests, Personal, Other, Travel expenses, including accommodations: Pfizer. C. Chung: Financial Interests, Personal, Advisory Role, Advisory/Consultancy: Pfizer; Financial Interests, Personal, Advisory Board, Advisory/Consultancy: Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau, Speaker Bureau/Expert Testimony: Roche. H. Iwata: Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo; Financial Interests, Personal, Advisory Role, Advisory/Consultancy: Daiichi Sankyo; Financial Interests, Personal, Research Grant: Daiichi Sankyo; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Advisory Role, Advisory/Consultancy: AstraZeneca; Financial Interests, Personal, Research Grant: AstraZeneca. E. Hamilton: Financial Interests, Institutional, Advisory Role: Genentech/Roche, Boehringer Ingelheim, Novartis, Dantari, Lilly, Merck, Puma Biotechnology, Silverback Therapeutics, CytomX, Pfizer, Mersana, Black Diamond, H3 Biomedicine, Daiichi Sankyo, AstraZeneca, Arvinas, Deciphera Pharmaceuticals, Eisai, Seagen; Financial Interests, Institutional, Research Grant: Paid to institution - OncoMed, Genentech/Roche, Zymeworks, Rgenix, ArQule, Clovis, Silverback Therapeutics, Millenium, Acerta Pharma, Sermonix Pharmaceuticals, Torque, Black Diamond, Karyopharm, Infinity Pharmaceuticals, Curis, Syndax, Novartis, Boehringe. G. Curigliano: Financial Interests, Personal, Other, Honoraria: Roche, Pfizer, Lilly, AstraZeneca, Daichi Sankyo, Ellipsis, Roche, Veracyte, BMS, Merck; Financial Interests, Personal, Advisory Role: Roche, Pfizer, Lilly, AstraZeneca, Daichi Sankyo, Ellipsis, Roche, Veracyte, BMS, Merck; Financial Interests, Personal, Speaker’s Bureau: Roche, Pfizer, Lilly, AstraZeneca , Daichi Sankyo, Roche, Merck; Financial Interests, Personal, Other, Travel Expenses: Roche, Pfizer. B. Xu: Financial Interests, Personal, Advisory Role, Consultant: Roche; Financial Interests, Personal, Speaker’s Bureau: Astra, Pfizer, Eisai. C. Lee: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. Y. Liu: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo. J. Cathcart: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. E. Bako: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. S. Verma: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. S.A. Hurvitz: Financial Interests, Institutional, Research Grant: Ambrx; Financial Interests, Institutional, Principal Investigator: Ambrx; Financial Interests, Institutional, Principal Investigator: Arvinas; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Bayer; Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator: Dignitana; Financial Interests, Institutional, Principal Investigator: Genentech/Roche; Financial Interests, Institutional, Principal Investigator: Gilead; Financial Interests, Institutional, Principal Investigator: GSK; Financial Interests, Institutional, Principal Investigator: Immunomedics; Financial Interests, Institutional, Principal Investigator: Lilly; Financial Interests, Institutional, Principal Investigator: Macrogenics; Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Institutional, Principal Investigator: OBI Pharma; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Principal Investigator: Phoenix Molecular Designs, Ltd; Financial Interests, Institutional, Principal Investigator: Pieris; Financial Interests, Institutional, Principal Investigator: PUMA; Financial Interests, Institutional, Principal Investigator: Radius; Financial Interests, Institutional, Research Grant: Samumed; Financial Interests, Institutional, Principal Investigator: Sanofi; Financial Interests, Institutional, Principal Investigator: Seattle Genetics; Financial Interests, Institutional, Principal Investigator: Zymeworks. All other authors have declared no conflicts of interest.

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Presidential symposium

Invited Discussant LBA1

Speakers
  • Shanu Modi (New York, NY, United States of America)
Lecture Time
15:20 - 15:35
Session Name
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Sat, 18.09.2021
Time
15:05 - 16:35
Presidential symposium

LBA2_PR - Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for persistent, recurrent, or metastatic cervical cancer: Randomized, double-blind, phase III KEYNOTE-826 study

Presentation Number
LBA2_PR
Speakers
  • Nicoletta Colombo (Milan, Italy)
Lecture Time
15:35 - 15:50
Session Name
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Sat, 18.09.2021
Time
15:05 - 16:35

Abstract

Background

Pembrolizumab (pembro) shows efficacy in patients (pts) with previously treated, PD-L1–positive advanced cervical cancer. In KEYNOTE-826 (NCT03635567), we evaluated the efficacy and safety of pembro + chemotherapy (chemo) ± bevacizumab (bev) for recurrent, persistent, or metastatic cervical cancer.

Methods

Eligible adults with persistent, recurrent, or metastatic cervical cancer not previously treated with systemic chemo (prior radiosensitizing chemo allowed) and not amenable to curative treatment were randomized 1:1 to pembro 200 mg or placebo Q3W for ≤35 cycles added to chemo (paclitaxel + cisplatin or carboplatin) ± bev. Pts were stratified by metastatic status at diagnosis, planned bev use, and PD-L1 combined positive score (CPS). Dual primary end points were PFS per RECIST v1.1 assessed by investigator review and OS, each tested sequentially in the PD-L1 CPS ≥1, all-comer, and CPS ≥10 populations. All data are from the protocol-specified first interim analysis (May 3, 2021 data cutoff).

Results

From Nov 2018 to Jan 2020, 617 pts were randomized to pembro + chemo (N = 308; 63.6% with bev) or placebo + chemo (N = 309; 62.5% with bev); 548 (88.8%) pts had PD-L1 CPS ≥1 and 317 (51.4%) had CPS ≥10. Pembro + chemo significantly improved PFS and OS in the CPS ≥1, all-comer, and CPS ≥10 populations (Table). The pembro + chemo benefit was seen regardless of bev use. Grade ≥3 AE incidence was 81.8% in the pembro + chemo arm and 75.1% in the placebo + chemo arm. The most common grade ≥3 AEs were anemia (30.3% vs 26.9%) and neutropenia (12.4% vs 9.7%).

PD-L1 CPS ≥1 All-Comer PD-L1 CPS ≥10
Pembro + Chemo(N = 273) Placebo + Chemo(N = 275) Pembro + Chemo(N = 308) Placebo + Chemo(N = 309) Pembro + Chemo(N = 158) Placebo + Chemo(N = 159)
PFS per RECIST v1.1 by investigator review
Median, mo 10.4 8.2 10.4 8.2 10.4 8.1
12-mo rate, % 45.5 34.1 44.7 33.5 44.6 33.5
HR (95% CI) 0.62 (0.50-0.77); P < 0.001 0.65 (0.53-0.79); P < 0.001 0.58 (0.44-0.77); P < 0.001
OS
Median, mo NR 16.3 24.4 16.5 NR 16.4
24-mo rate, % 53.0 41.7 50.4 40.4 54.4 44.6
HR (95% CI) 0.64 (0.50-0.81); P < 0.001 0.67 (0.54-0.84); P < 0.001 0.61 (0.44-0.84); P = 0.001

Conclusions

Pembro + chemo provided statistically significant, clinically meaningful PFS and OS improvements in pts with persistent, recurrent, or metastatic cervical cancer, regardless of PD-L1 expression and concomitant bev use. Along with a manageable safety profile, these data suggest pembro + chemo ± bev may be a new standard of care for this population.

Clinical trial identification

NCT03635567.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Melanie Leiby of Merck & Co., Inc., Kenilworth, NJ, USA. This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

N. Colombo: Financial Interests, Invited Speaker: AstraZeneca, MSD/Merck, Novartis, Clovis, GSK; Financial Interests, Advisory Board: Roche, Pharmamar, AstraZeneca, MSD/Merck, Clovis Oncology, Tesaro, GSK, Pfizer, Takeda, BIOCAD, Immunogen, Mersana, Eisai, Oncxerna; Financial Interests, Funding: Roche, AstraZeneca. C. Dubot: Financial Interests, Institutional, Funding: MSD. D. Lorusso: Financial Interests, Personal and Institutional, Funding, funding/advisory role: MSD; Financial Interests, Personal and Institutional, Funding, funding/advisory role: Clovis Oncology; Financial Interests, Personal and Institutional, Funding, funding/advisory role: GSK; Financial Interests, Personal and Institutional, Funding, funding/advisory role: AstraZeneca; Financial Interests, Personal and Institutional, Funding, funding/advisory role: Pharmamar; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Amgen. V. Cáceres: Financial Interests, Institutional, Funding: MSD. K. Hasegawa: Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Role: MSD. R. Shapira-Frommer: Financial Interests, Institutional, Funding: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Clovis Oncology; Financial Interests, Personal, Advisory Board: VBL Therapeutics. K.S. Tewari: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Tesaro; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Tesaro; Financial Interests, Personal, Speaker’s Bureau: Clovis; Financial Interests, Personal, Speaker’s Bureau: Eisai. P. Salman: Financial Interests, Institutional, Principal Investigator: MSD. E. Hoyos: Financial Interests, Institutional, Funding: MSD. E. Yañez: Financial Interests, Institutional, Funding: MSD. M. Gumus: Financial Interests, Institutional, Funding: MSD. M. Olivera Hurtado de Mendoza: Financial Interests, Institutional, Funding: MSD; Financial Interests, Personal and Institutional, Principal Investigator: MSD. V. Samouëlian: Financial Interests, Institutional, Funding: MSD. V. Castonguay: Financial Interests, Personal, Advisory Board: MSD. A. Arkhipov: Financial Interests, Institutional, Funding: MSD; Financial Interests, Personal, Principal Investigator: MSD. S. Toker: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Stocks/Shares: Merck Sharp & Dohme Corp. K. Li: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp. S.M. Keefe: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Stocks/Shares: Merck Sharp & Dohme Corp. B.J. Monk: Financial Interests, Institutional, Funding: MSD; Financial Interests, Personal, Leadership Role: US Oncology; Financial Interests, Personal, Other, honoraria/consulting: AbbVie; Financial Interests, Personal and Institutional, Other, honoraria/consulting, funding: Advaxis; Financial Interests, Personal, Other, honoraria/consulting: Agenus; Financial Interests, Personal, Other, honoraria/consulting: Akeso Biopharma; Financial Interests, Personal and Institutional, Other, honoraria/consulting, funding: Amgen; Financial Interests, Personal, Other, honoraria/consulting: Aravive; Financial Interests, Personal and Institutional, Other, honoraria/consulting/speakers' bureau, funding: AstraZeneca; Financial Interests, Personal, Other, honoraria/consulting: Asymmetric Therapeutics; Financial Interests, Personal, Other, honoraria/consulting: Boston Biomedical; Financial Interests, Personal, Other, honoraria/consulting: ChemoID; Financial Interests, Personal, Other, honoraria/consulting/speakers' bureau: Clovis Oncology; Financial Interests, Personal, Other, honoraria/consulting: Deciphera Pharmaceuticals; Financial Interests, Personal, Other, honoraria/consulting/speakers' bureau: Eisai; Financial Interests, Personal, Other, honoraria: Elevar Therapeutics; Financial Interests, Personal, Other, honoraria/consulting: Geistlich Pharma; Financial Interests, Personal, Advisory Role: ChemoCare; Financial Interests, Personal, Other, honoraria/consulting: Genmab/Seattle Genetics; Financial Interests, Personal, Other, honoraria/consulting: GOG Foundation; Financial Interests, Personal, Other, honoraria/consulting: Gradalis; Financial Interests, Personal and Institutional, Other, honoraria/consulting, funding: ImmunoGen; Financial Interests, Personal, Other, honoraria/consulting: Immunomedics; Financial Interests, Personal, Other, honoraria/consulting: Incyte; Financial Interests, Personal, Other, honoraria/consulting: Iovance Biotherapeutics; Financial Interests, Personal, Other, honoraria/consulting: Karyopharm Therapeutics; Financial Interests, Personal, Other, honoraria/consulting: Laekna Health Care; Financial Interests, Personal, Other, honoraria/consulting/speakers' bureau: Merck; Financial Interests, Personal, Other, honoraria/consulting: Mersana; Financial Interests, Personal, Other, honoraria/consulting: Myriad Pharmaceuticals; Financial Interests, Personal, Other, honoraria/consulting: Novocure; Financial Interests, Personal and Institutional, Other, honoraria/consulting, funding: Nucana; Financial Interests, Personal, Other, honoraria/consulting: Oncomed; Financial Interests, Personal, Other, honoraria/consulting: Oncoquest; Financial Interests, Personal, Other, honoraria/consulting: Oncosec; Financial Interests, Personal, Other, honoraria/consulting: Perthera; Financial Interests, Personal and Institutional, Other, honoraria/consulting, funding: Pfizer; Financial Interests, Personal, Other, honoraria/consulting: Puma Biotechnology; Financial Interests, Personal and Institutional, Other, honoraria/consulting, funding: Regeneron; Financial Interests, Personal, Other, honoraria/consulting/speakers' bureau: Roche/Genentech; Financial Interests, Personal, Other, honoraria/consulting: Senti Biosciences; Financial Interests, Personal, Other, honoraria: Starton Therapeutics; Financial Interests, Personal, Other, honoraria/consulting: Takeda; Financial Interests, Personal, Other, honoraria/consulting: Tarveda Therapeutics; Financial Interests, Personal, Other, honoraria/consulting/speakers' bureau: Tesaro/GSK; Financial Interests, Personal, Other, honoraria/consulting: Vascular Biogenics; Financial Interests, Personal, Other, honoraria/consulting: Vavotar Life Sciences; Financial Interests, Personal, Other, honoraria/consulting: Vigeo Therapeutics; Financial Interests, Personal, Advisory Role: Sorrento Therapeutics; Financial Interests, Institutional, Funding: Array BioPharma; Financial Interests, Institutional, Funding: Genentech; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Institutional, Funding: Morphotek; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Tesaro.

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Presidential symposium

Invited Discussant LBA2_PR

Speakers
  • Mansoor Raza Mirza (Copenhagen, Denmark)
Lecture Time
15:50 - 16:05
Session Name
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Sat, 18.09.2021
Time
15:05 - 16:35
Presidential symposium

LBA3_PR - Pembrolizumab versus placebo after complete resection of high-risk stage II melanoma: Efficacy and safety results from the KEYNOTE-716 double-blind phase III trial

Presentation Number
LBA3_PR
Speakers
  • Jason J. Luke (Pittsburgh, United States of America)
Lecture Time
16:05 - 16:20
Session Name
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Sat, 18.09.2021
Time
15:05 - 16:35

Abstract

Background

Current standard of care for patients (pts) after resection of high-risk stage II melanoma is observation. In the phase 3 double-blind KEYNOTE-716 trial we evaluated pembrolizumab (pembro) versus placebo in pts with resected AJCC-8 stage IIB or IIC melanoma. We present results of the first recurrence-free survival (RFS) interim analysis.

Methods

Eligible pts aged ≥12 years with complete resection of cutaneous stage IIB or IIC melanoma with negative sentinel lymph node biopsy were randomized 1:1 to pembro 200 mg (2 mg/kg for pediatric pts) or placebo Q3W for 17 cycles (up to 1 year). Randomization was stratified by T category 3b, 4a, 4b (adults) with a separate stratum for pediatric pts. Treatment continued until disease recurrence or unacceptable toxicity. The primary endpoint was RFS per investigator assessment. Safety was also evaluated. The data cutoff date for the interim analysis was December 4, 2020.

Results

Overall, 976 pts (64% stage IIB; 34.8% stage IIC) were randomized (487 pembro; 489 placebo). At median follow-up of 14.4 months, pembro significantly prolonged RFS vs placebo (HR 0.65, 95% CI 0.46-0.92; P=0.00658; median not reached for both). 54 (11.1%) vs 82 (16.8%) pts had a recurrence with almost halving of distant recurrence events in the pembro (23) vs placebo (38) group. The 12-month RFS rate was 90.5% vs 83.1%. Grade ≥3 any-cause AEs occurred in 125 (25.9%) vs 83 (17.1%) pts in the pembro vs placebo group. Grade ≥3 drug-related AEs occurred in 78 (16.1%) vs 21 (4.3%) pts; 74 (15.3%) vs 12 (2.5%) discontinued due to a drug-related AE. No deaths due to any-cause AE or drug-related AEs occurred with pembro; four deaths due to any-cause AEs occurred with placebo. Immune-mediated AEs occurred in 36.2% vs 8.4%, most commonly hypothyroidism (15.7% vs 3.5%) and hyperthyroidism (10.4% vs 0.6%). Most were grade 1-2 in severity.

Conclusions

Adjuvant pembrolizumab for resected stage IIB and IIC melanoma decreased the risk of disease recurrence or death by 35% compared with placebo and was associated with significantly prolonged RFS and a favorable benefit-risk profile.

Clinical trial identification

NCT03553836; EudraCT 2018-000669-35; First posted: June 12, 2018.

Editorial acknowledgement

Editoral assistance was provided by Luana Atherly-Henderson, PhD, CMPP an employee of Merck Sharp & Dohme, Corp.

Legal entity responsible for the study

Merck Sharp & Dohme Corp.

Funding

Merck Sharp & Dohme Corp.

Disclosure

J.J. Luke: Financial Interests, Personal, Advisory Board: 7 Hills; Financial Interests, Personal, Advisory Board: Fstar; Financial Interests, Personal, Advisory Board: RefleXion; Financial Interests, Personal, Advisory Board: Alphamab Oncology; Financial Interests, Personal, Advisory Board: Arch Oncology; Financial Interests, Personal, Advisory Board: Kanaph; Financial Interests, Personal, Advisory Board: Onc.AI; Financial Interests, Personal, Advisory Board: Pyxis; Financial Interests, Personal, Advisory Board: Tempest; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: Alnylam; Financial Interests, Personal, Advisory Board: Array; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Checkmate; Financial Interests, Personal, Advisory Board: Cstone; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Board: Flame; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Advisory Board: Kadmon; Financial Interests, Personal, Advisory Board: KSQ; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Immunocore; Financial Interests, Personal, Advisory Board: Inzen; Financial Interests, Personal, Advisory Board: Crown; Financial Interests, Personal, Advisory Board: Macrogenics; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Mersana; Financial Interests, Personal, Advisory Board: Nektar; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: Ribon; Financial Interests, Personal, Advisory Board: Rubius; Financial Interests, Personal, Advisory Board: Silicon; Financial Interests, Personal, Advisory Board: Synlogic; Financial Interests, Personal, Advisory Board: TRex; Financial Interests, Personal, Advisory Board: Werewolf; Financial Interests, Personal, Advisory Board: Xilio; Financial Interests, Personal, Advisory Board: Xencor; Financial Interests, Personal, Ownership Interest: Actym; Financial Interests, Personal, Ownership Interest: Alphamab Oncology; Financial Interests, Personal, Ownership Interest: Arch Oncology; Financial Interests, Personal, Ownership Interest: Kanaph; Financial Interests, Personal, Ownership Interest: Mavu; Financial Interests, Personal, Ownership Interest: Onc.AI; Financial Interests, Personal, Ownership Interest: Pyxis; Financial Interests, Personal, Ownership Interest: Tempest; Financial Interests, Institutional, Invited Speaker: AbbVie; Financial Interests, Institutional, Research Grant: Agios; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Invited Speaker: Astellas; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Corvus; Financial Interests, Institutional, Invited Speaker: EMD Serono; Financial Interests, Institutional, Invited Speaker: Genmab; Financial Interests, Institutional, Invited Speaker: Ikena; Financial Interests, Institutional, Invited Speaker: Immatics; Financial Interests, Institutional, Invited Speaker: Incyte; Financial Interests, Institutional, Invited Speaker: Kadmon; Financial Interests, Institutional, Invited Speaker: KAHR; Financial Interests, Institutional, Invited Speaker: Macrogenics; Financial Interests, Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Invited Speaker: Moderna; Financial Interests, Institutional, Invited Speaker: Nektar; Financial Interests, Institutional, Invited Speaker: Numab; Financial Interests, Institutional, Invited Speaker: Replimmune; Financial Interests, Institutional, Invited Speaker: Rubius; Financial Interests, Institutional, Invited Speaker: Fstar; Financial Interests, Institutional, Invited Speaker: Synlogic; Financial Interests, Institutional, Invited Speaker: Takeda; Financial Interests, Institutional, Invited Speaker: Trishula; Financial Interests, Institutional, Invited Speaker: Tizona; Financial Interests, Institutional, Invited Speaker: Xencor. P. Rutkowski: Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Blueprint Medicines; Financial Interests, Personal, Invited Speaker: Philogen. P. Queirolo: Financial Interests, Advisory Role: Bristol Myers Squibb; Financial Interests, Advisory Role: MSD; Financial Interests, Advisory Role: Merck; Financial Interests, Advisory Role: Novartis; Financial Interests, Advisory Role: Pierre Fabre; Financial Interests, Advisory Role: Sun Pharma; Financial Interests, Advisory Role: Sanofi-Regeneron; Financial Interests, Advisory Role: Roche. M. Del Vecchio: Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Advisory Role: Sanofi. J. Mackiewicz: Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: MSD. V. Chiarion Sileni: Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Merck-Serono; Financial Interests, Personal, Advisory Role: Pierre-Fabre; Financial Interests, Personal, Other, Travel expenses: BMS; Financial Interests, Personal, Other, Travel expenses: Pierre Fabre. L. de la Cruz Merino: Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Institutional, Principal Investigator: Celgene; Financial Interests, Personal, Principal Investigator: Roche; Financial Interests, Personal, Other, Travel expenses: Roche. M.A. Khattak: Financial Interests, Personal, Principal Investigator: Merck. D. Schadendorf: Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Sandoz; Financial Interests, Personal, Invited Speaker: Philogen; Financial Interests, Personal, Invited Speaker: UltimoVacs; Financial Interests, Personal, Invited Speaker: Neracare; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: 4SC; Financial Interests, Personal, Invited Speaker: InFlarX; Financial Interests, Personal, Invited Speaker: Immunocore; Financial Interests, Personal, Invited Speaker: Nektar; Financial Interests, Personal, Invited Speaker: OncoSec; Financial Interests, Personal, Invited Speaker: Regeneron; Financial Interests, Personal, Invited Speaker: Sun Pharma; Financial Interests, Personal, Invited Speaker: Array; Financial Interests, Personal, Invited Speaker: Replimune; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Sandoz; Financial Interests, Personal, Advisory Role: Philogen; Financial Interests, Personal, Advisory Role: UltimoVacs; Financial Interests, Personal, Advisory Role: Neracare; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: 4SC; Financial Interests, Personal, Advisory Role: InFlarX; Financial Interests, Personal, Advisory Role: Imunocore; Financial Interests, Personal, Advisory Role: Nektar; Financial Interests, Personal, Advisory Role: OncoSec; Financial Interests, Personal, Advisory Role: Regeneron; Financial Interests, Personal, Advisory Role: SunPharma; Financial Interests, Personal, Advisory Role: Array; Financial Interests, Personal, Advisory Role: Replimmune; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: BMS. G.V. Long: Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Personal, Advisory Role: Aduro Biotech Inc; Financial Interests, Personal, Advisory Role: Amgen Inc; Financial Interests, Personal, Advisory Role: Array Biopharma Inc; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Evaxion Biotech A/S; Financial Interests, Personal, Advisory Role: Hexel AG; Financial Interests, Personal, Advisory Role: Highlight Therapeutics SL; Financial Interests, Personal, Advisory Role: Merck Sharp Dohme; Financial Interests, Personal, Advisory Role: Novartis Pharma AG; Financial Interests, Personal, Advisory Role: OncoSec; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role: QBiotics Group Limited; Financial Interests, Personal, Advisory Role: Regeneron Pharmaceutical Inc; Financial Interests, Personal, Advisory Role: SkylineDX BV; Financial Interests, Personal, Advisory Role: Specialised Therapeutics Australia Pty Ltd. P.A. Ascierto: Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Institutional, Principal Investigator: Bristol Myers Squibb; Financial Interests, Institutional, Principal Investigator: Roche-Genentech; Financial Interests, Institutional, Principal Investigator: Array; Financial Interests, Institutional, Principal Investigator: Sanofi; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Roche-Genentech; Financial Interests, Personal, Advisory Role: Merck Sharp Dohme; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Merck-Serono; Financial Interests, Personal, Advisory Role: Pierre-Fabre; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Sun Pharma; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Idera; Financial Interests, Personal, Advisory Role: Sandoz; Financial Interests, Personal, Advisory Role: Immunocore; Financial Interests, Personal, Advisory Role: 4SC; Financial Interests, Personal, Advisory Role: Italfarmaco; Financial Interests, Personal, Advisory Role: Nektar; Financial Interests, Personal, Advisory Role: Boehringer-Ingelheim; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Regeneron; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Oncosec; Financial Interests, Personal, Advisory Role: Nouscom; Financial Interests, Personal, Advisory Role: Lunaphore; Financial Interests, Personal, Advisory Role: Seagen; Financial Interests, Personal, Advisory Role: iTeos. M. Mandala: Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Institutional, Principal Investigator: Roche; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Pierre Fabre. F. De Galitiis: Financial Interests, Personal, Principal Investigator: Merck. V. Sondak: Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Institutional, Principal Investigator: Neogene Therapeutics; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Regeneron; Financial Interests, Personal, Advisory Role: Replimune. R.A. Scolyer: Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Personal, Advisory Role: Evaxion; Financial Interests, Personal, Advisory Role: Provectus; Financial Interests, Personal, Advisory Role: Obiotics; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Merck Sharp and Dohme; Financial Interests, Personal, Advisory Role: NeraCare; Financial Interests, Personal, Advisory Role: Amgen Inc; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Myriad Genetics; Financial Interests, Personal, Advisory Role: GlaxoSmithKline. J.M. Kirkwood: Financial Interests, Personal, Principal Investigator: Merck. K. Chen: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. N. Ibrahim: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. S. Ahsan: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. A.M.M. Eggermont: Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Personal, Invited Speaker: Biocad; Financial Interests, Personal, Advisory Board: BioInvent; Financial Interests, Personal, Advisory Board: BioNTech; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: CYTimmune; Financial Interests, Personal, Advisory Board: Dash Therapeutics; Financial Interests, Personal, Advisory Board: CatalYm; Financial Interests, Personal, Advisory Board: Ellipses; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: IO Biotech; Financial Interests, Personal, Advisory Board: ISA Pharmaceuticals; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Nektar; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: RiverD; Financial Interests, Personal, Advisory Board: Sellas; Financial Interests, Personal, Advisory Board: Skyline Dx; Financial Interests, Personal, Advisory Board: TxDiscovery; Financial Interests, Personal, Advisory Board: TigaTx; Financial Interests, Personal, Advisory Role: Biocad; Financial Interests, Personal, Advisory Role: BioInvent; Financial Interests, Personal, Advisory Role: BioNTech; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: CYTimmune; Financial Interests, Personal, Advisory Role: Dash Therapeutics; Financial Interests, Personal, Advisory Role: CatalYm; Financial Interests, Personal, Advisory Role: Ellipses; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: IO Biotech; Financial Interests, Personal, Advisory Role: ISA Pharmaceuticals; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Nektar; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: RiverD; Financial Interests, Personal, Advisory Role: Sellas; Financial Interests, Personal, Advisory Role: Skyline Dx; Financial Interests, Personal, Advisory Role: TxDiscovery; Financial Interests, Personal, Advisory Role: TigaTx; Financial Interests, Personal, Speaker’s Bureau: Biocad; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Stocks/Shares: Dash Therpeutics; Financial Interests, Personal, Stocks/Shares: IO Biotech; Financial Interests, Personal, Stocks/Shares: SkylineDx.

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Presidential symposium

Invited Discussant LBA3_PR

Speakers
  • Omid Hamid (Los Angeles, CA, United States of America)
Lecture Time
16:20 - 16:35
Session Name
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Sat, 18.09.2021
Time
15:05 - 16:35