Found 9 Presentations For Request "Changhoon Yoo"

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Biliary tract cancer, incl. cholangiocarcinoma

55P - Final results from the NIFTY trial, a phase IIb, randomized, open-label study of liposomal Irinotecan (nal-IRI) plus fluorouracil (5-FU)/leucovorin (LV) in patients (pts) with previously treated metastatic biliary tract cancer (BTC)

Presentation Number
55P
Speakers
  • Changhoon Yoo (Seoul, Korea, Republic of)
Date
Mon, 12.09.2022

Abstract

Background

The NIFTY trial showed that nal-IRI plus 5-FU/LV significantly improved the blinded-independent central review (BICR)- and investigator-assessed progression-free survival (PFS) and overall survival (OS) compared with 5-FU/LV. An updated analysis (data cutoff: 31 DEC 2021) was performed to assess the long-term efficacy outcomes (extension follow-up of 1.3 years). As there was a concern about the large discrepancy rates (30%) between BICR and investigator review in the previous analysis, BICR was performed again by three independent radiologists with more experience in clinical trials and also through external monitoring.

Methods

Pts with > 19 yrs, ECOG PS 0-1, metastatic BTC, and disease progression on prior GemCis were eligible. Pts were randomized 1:1 to nal-IRI plus 5-FU/LV or 5-FU/LV, every 2 weeks. Tumor response was evaluated per RECIST v1.1, every 6 wks.

Results

Between SEP 2018 and FEB 2020, 88 and 86 pts were included in nal-IRI plus 5-FU/LV and 5-FU/LV groups, respectively. With median follow-up of 6.1 mo (IQR 3.5-12.6), median PFS per BICR in nal-IRI plus 5-FU/LV group and 5-FU/LV group was 3.9 mo (95% CI, 2.6-4.7) and 1.5 mo (1.2-1.9), respectively (HR=0.38 [0.26-0.54], p<0.0001); median PFS per investigator review was 3.9 mo (2.7-5.2) and 1.6 mo (1.3-2.2), respectively (HR=0.51 [0.36-0.71], p<0.0001). Median OS was 8.6 mo (5.4-10.5) and 5.3 mo (4.7-7.2), respectively (HR=0.68 [0.48-0.95], p=0.024). ORR was 12.5% and 3.5% per BICR, respectively (p=0.043) and 19.3% and 2.3% per investigator review, respectively (p=0.0002). The discordance rate for tumor progression date between BICR and investigators was 10.7%. In multivariate analyses for prognostic factors, bone mets was associated with poor PFS; male, CA 19-9 > median, elevated CRP, and albumin > median were associated with poor OS; prior GemCis duration > median was associated with better OS.

Conclusions

The survival benefits of 2nd line nal-IRI plus 5-FU/LV versus 5-FU/LV were maintained over an extended follow-up in BTC pts.

Clinical trial identification

NCT03524508 Release date: May 14, 2018.

Legal entity responsible for the study

The authors.

Funding

Servier and HK Inno.N.

Disclosure

C. Yoo: Financial Interests, Personal, Invited Speaker: Bayer, Celgene, Eisai, Ipsen, Servier, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca. G.K. Abou-Alfa: Financial Interests, Personal, Advisory Board: Adicet, Alnylam, AstraZeneca, Autem, Beigene, Berry Genomics, Boehringer Ingelheim, Celgene, Cend, CytomX, Eisai, Eli Lilly, Exelixis, Flatiron, Genentech/Roche, Genoscience, Helio, Helsinn, Incyte, Ipsen, Merck, Nerviano, Newbridge, Novartis, QED, Redhill, Rafael, Servier, Silenseed, Sobi, Vector, Yiviva; Financial Interests, Personal, Other, IP License: PCT/US2014/031545 filed on March 24, 2014, and priority application Serial No.: 61/804,907; Filed: March 25, 2013; Financial Interests, Institutional, Research Grant: Arcus, AstraZeneca, BioNtech, BMS, Celgene, Flatiron, Genentech/Roche, Genoscience, Incyte, Polaris, Puma, QED, Silenseed, Yiviva; Non-Financial Interests, Principal Investigator: AstraZeneca, Yiviva, QED. All other authors have declared no conflicts of interest.

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Gynaecological cancers

591P - Feasibility of longitudinal monitoring of whole blood-based circulating tumour DNA (ctDNA) in patients with endometrial cancer

Presentation Number
591P
Speakers
  • Yoo-Na Kim (Seoul, Korea, Republic of)
Date
Sun, 11.09.2022

Abstract

Background

For endometrial cancer patients, liquid biopsy based on whole blood is less invasive than endometrial biopsy and has the potential to be serially collected for monitoring after hysterectomy. Thus, we analyzed serially obtained ctDNA from endometrial cancer patients undergoing staging operation.

Methods

Patients diagnosed with endometrial cancer since January 2021 were prospectively enrolled. Whole blood samples were collected prior to staging operation and every three months thereafter. Control samples were obtained from patients undergoing hysterectomy for benign indication. ctDNA was extracted and analyzed with a custom panel covering 100 endometrial cancer-related genes. Prepared libraries were sequenced using NovaSeq 6000 System (Illumina) and analyzed using PiSeq analysis (Dxome).

Results

A total of 91 patients, including 72 endometrial cancer and 19 control patients, contributed 154 samples for analysis. Endometrial cancer patients consisted of 43 patients with uterine confined disease (stage IA, 32%; IB, 17%; II, 5%) and 23 patients with advanced disease (stage III, 18%; IV or recurrent, 28%). The detection rate was higher in advanced (65%) compared to uterine confined disease (29%) (p-value=0.01). Stratified by clinical stage, sensitivity and specificity with respect to cancer detection were 61% and 94.6% for advanced disease and 23% and 94.7% for uterine confined disease, respectively. Genomic landscape analysis of 30 patients harboring pathogenic mutations at baseline highlighted frequently altered genes such as TP53 (43%), PTEN (37%), ARID1A (23%), PIK3CA (13%). Other interesting genes included MSH6 (7%), and CTNNB1 (3%). Analysis of 35 patients with serial samples showed that among 13 patients with detectable somatic mutation at baseline, negative conversion was found in 8 patients and persistent mutation in 5 patients.

Conclusions

Detection and monitoring by whole blood-based ctDNA is feasible in endometrial cancer patients, especially those with advanced stage disease who may benefit from heightened surveillance after surgery. Genomic mutations as well as their trend may help tailor adjuvant therapy. Updated analysis with additional patients will be shared at the conference.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Biomarkers (agnostic)

94P - Performance validation of an artificial intelligence-powered programmed death-ligand 1 (PD-L1) combined positive score analyzer in urothelial cancer

Presentation Number
94P
Speakers
  • Jeong Hwan Park (Seoul, Korea, Republic of)
Date
Sat, 10.09.2022

Abstract

Background

Programmed death-ligand 1 (PD-L1) expression is a predictive marker for immune checkpoint inhibitors (ICI) treatment in urothelial carcinoma (UC). The combined positive score (CPS) is a method to evaluate the expression level of PD-L1 in UC. This study aimed to evaluate the performance of an artificial intelligence (AI)-powered PD-L1 CPS analyzer on UC compared to the pathologists.

Methods

Lunit SCOPE PD-L1 CPS was developed with 3.02 x 105 tumor cells and 3.49 x 105 immune cells from PD-L1 immunohistochemistry-stained whole-slide images (WSI) of UC from multiple institutions, annotated by 94 pathologists. The tissue area segmentation and cell detection AI models were developed based on a semantic segmentation algorithm, which includes an atrous spatial pyramid pooling block. To validate the model, a total of 543 PD-L1 stained UC WSIs were obtained from three university hospitals (n = 245, 205, and 93 in each). Three uropathologists evaluated slide-level CPS and assigned CPS high or low (10% cutoff value). The agreement (high or low) or correlation (continuous value) of CPS between the pathologists and the AI prediction was evaluated.

Results

All pathologists agreed on the CPS level in 446 out of 543 cases (82.1%). The agreement or correlation between either of the two pathologists was 87.1%−89.9% (Table). AI model accuracy to pathologists' consensus was 88.8%, and the Intraclass correlation coefficient (ICC) value between the AI model CPS value and the average CPS value of pathologists was 0.94 (95% confidence interval [CI] 0.93−0.95). The performance of the AI model was similar with each individual pathologist (accuracy / ICC; 85.1% / 0.94, 86.6% / 0.90, and 87.1% / 0.93, respectively) and individual hospital dataset (accuracy / ICC; 89.4% / 0.92, 87.8% / 0.95, and 89.2% / 0.92, respectively).

Comparison Agreement (10% cutoff) Correlation (ICC (2,k)) (95% CI)
Pathologist A vs. B 87.1% 0.91 (0.90−0.93)
Pathologist A vs. C 89.9% 0.96 (0.96−0.97)
Pathologist B vs. C 87.3% 0.92 (0.90−0.93)
Pathologist consensus vs. AI model 88.8% 0.94 (0.93−0.95)

Conclusions

This study demonstrates that an AI-powered PD-L1 CPS analyzer can classify CPS levels in UC comparable to pathologists.

Legal entity responsible for the study

Lunit.

Funding

Lunit.

Disclosure

S.I. Cho: Financial Interests, Personal, Stocks/Shares: Lunit; Financial Interests, Personal, Full or part-time Employment: Lunit. W. Jung: Financial Interests, Personal, Stocks/Shares: Lunit; Financial Interests, Personal, Full or part-time Employment: Lunit. S. Kim: Financial Interests, Personal, Full or part-time Employment: Lunit. G. Park: Financial Interests, Personal, Stocks/Shares: Lunit; Financial Interests, Personal, Full or part-time Employment: Lunit. S. Song: Financial Interests, Personal, Stocks/Shares: Lunit; Financial Interests, Personal, Full or part-time Employment: Lunit. C. Kang: Financial Interests, Personal, Full or part-time Employment: Lunit. M. Ma: Financial Interests, Personal, Full or part-time Employment: Lunit; Financial Interests, Personal, Stocks/Shares: Lunit. D. Yoo: Financial Interests, Personal, Stocks/Shares: Lunit; Financial Interests, Personal, Full or part-time Employment: Lunit. K. Paeng: Financial Interests, Personal, Stocks/Shares: Lunit; Financial Interests, Personal, Full or part-time Employment: Lunit. C. Ock: Financial Interests, Personal, Stocks/Shares: Lunit, Ybiologics; Financial Interests, Personal, Full or part-time Employment: Lunit; Financial Interests, Personal, Member of the Board of Directors: Ybiologics. All other authors have declared no conflicts of interest.

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Melanoma and other skin tumours

814P - Phase II study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC): Final analysis from EMPOWER-CSCC-1 groups 1, 2 and 3

Presentation Number
814P
Speakers
  • Michael R. Migden (Houston, United States of America)
Date
Sat, 10.09.2022

Abstract

Background

Previous analyses from EMPOWER-CSCC-1 phase 2 study (NCT02760498) demonstrated substantial clinical benefit and an acceptable safety profile with cemiplimab in patients with locally advanced and metastatic CSCC. Here, we provide the final analysis from the study Groups 1, 2 and 3.

Methods

Patients received cemiplimab 3 mg/kg IV every 2 weeks for up to 96 weeks (Group 1, metastatic CSCC; Group 2, locally advanced CSCC) or cemiplimab 350 mg IV every 3 weeks for up to 54 weeks (Group 3, metastatic CSCC). The primary endpoint was objective response rate (ORR; complete + partial response) per independent central review (ICR). This is the final analysis and the final database lock occurred on 01 Mar 2022.

Results

A total of 193 patients were enrolled (Group 1, n=59; Group 2, n=78; Group 3, n=56). Tumour response per ICR, median progression-free survival (PFS) and overall survival (OS) (Table) remain generally consistent with the previous update (data cut-off: 11 Oct 2020). OS at 48 months is 61.8% (95% CI: 54.0-68.7). Overall median duration of response (DOR) was 41.3 months (Table). Fatigue (34.7%) was the most common treatment-emergent adverse event (TEAE) of any grade; hypertension (4.7%) was the most common Grade ≥3 TEAE.

Group 1 (mCSCC) 3 mg/kg Q2W (n=59) Group 2 (laCSCC) 3 mg/kg Q2W (n=78) Group 3 (mCSCC) 350 mg Q3W (n=56) Total (n=193)
Median duration of follow-up, months, (range) 18.5 (1.1–41.0) 15.5 (0.8–43.2) 17.3 (0.6–43.4) 15.7 (0.6–43.4)
ORR, %, (95% CI) 50.8 (37.5–64.1) 44.9 (33.6–56.6) 46.4 (33.0–60.3) 47.2 (39.9–54.4)
Complete response, n (%) 12 (20.3) 10 (12.8) 11 (19.6) 33 (17.1)
Partial response, n (%) 18 (30.5) 25 (32.1) 15 (26.8) 58 (30.1)
Median DOR, months (95% CI) NR (20.7–NE) 41.9 (20.5–54.6) 41.3 (40.8–46.3) 41.3 (38.8–46.3)
Median PFS, months (95% CI) 18.4 (7.3–53.2) 18.5 (11.1–43.8) 21.7 (3.8–43.3) 22.1 (10.4–32.3)
Median OS, months (95% CI) 57.7 (29.3–NE) NR (58.3–NE) 48.4 (29.5–NE) NR (56.0–NE)

CI, confidence interval; DOR, duration of response; NE, not evaluable; NR, not reached; ORR, objective response rate; OS, overall survival; PFS, progression-free survival.

Conclusions

The final update confirms the durable response, safety and efficacy of cemiplimab in patients with advanced CSCC. There were no new safety signals identified on longer follow-up. Cemiplimab remains a standard of care option for advanced CSCC.

Clinical trial identification

NCT02760498.

Editorial acknowledgement

Medical writing support and typesetting were provided by Sameen Yousaf, PhD, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc., and Sanofi.

Legal entity responsible for the study

Regeneron Pharmaceuticals, Inc., and Sanofi.

Funding

Regeneron Pharmaceuticals, Inc., and Sanofi.

Disclosure

M.R. Migden: Financial Interests, Personal, Other, honoraria and travel expenses: Regeneron Pharmaceuticals, Inc., Sanofi, Novartis, Genentech, Eli Lilly, Sun Pharma; Financial Interests, Institutional, Research Grant: Regeneron Pharmaceuticals, Inc., Novartis, Genentech, Eli Lilly. C. Schmults: Financial Interests, Personal, Other, steering committee membership: Castle Biosciences; Financial Interests, Personal, Other, steering committee membership and consultancy: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Other, consultancy: Sanofi; Financial Interests, Personal, Research Grant: Castle Biosciences, Regeneron Pharmaceuticals, Inc., Novartis, Genentech, Merck; Financial Interests, Personal, Other, chair: National Comprehensive Cancer Network. N. Khushanlani: Financial Interests, Personal, Research Grant: Regeneron, Bristol Myers Squibb, Merck, Novartis, Replimune, GlaxoSmithKline, HUYA, Celgene; Financial Interests, Personal, Advisory Board: Regeneron, Bristol Myers Squibb, Merck, Novartis, Iovance, Instil Bio, Castle Biosciences, Nektar, Incyte , AstraZeneca , Jounce Therapeutics; Financial Interests, Personal, Other, data safety monitoring committee: Incyte , AstraZeneca ; Financial Interests, Personal, Other, honoraria: Genzyme, NCCN (from Pfizer); Financial Interests, Personal, Other, honoraria/study steering committee: Nektar; Financial Interests, Personal, Stocks/Shares: Bellicum Pharmaceuticals, Amarin, Transenetrix. A. Guminski: Financial Interests, Personal, Other, personal fees and travel support: Bristol Myers Squibb, Sun Pharma; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Sun Pharma, Merck KGaA, Eisai , Pfizer; Financial Interests, Personal, Other, travel support: Astellas; Financial Interests, Personal, Other, clinical trial unit support: PPD Australia. A.L. Chang: Financial Interests, Personal, Advisory Role: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Research Grant: Regeneron Pharmaceuticals, Inc., Novartis, Galderma, Merck; Financial Interests, Personal, Other, consulting: Regeneron Pharmaceuticals, Inc., Merck; Financial Interests, Personal, Advisory Board: Merck. K. Lewis: Financial Interests, Personal, Research Grant: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Other, personal fees: Regeneron Pharmaceuticals, Inc. S.E. Bowyer: Financial Interests, Personal, Advisory Board: Sanofi ; Financial Interests, Personal, Sponsor/Funding: Bristol Myers Squibb , Merck Sharp & Dohme Australia. B.G.M. Hughes: Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, Pfizer, Roche, Eisai, Merck; Financial Interests, Institutional, Research Grant: Amgen. D. Schadendorf: Financial Interests, Personal, Other, institutional patients’ fees: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Advisory Board: Amgen , Leo Pharma, Roche, Novartis, Bristol Myers Squibb, Merck-EMD, Incyte , Pierre Fabre, Merck Sharp & Dohme, AstraZeneca, Pfizer , Array, Philiogen; Financial Interests, Personal, Other, speaker fee: Boehringer Ingelheim; Financial Interests, Personal, Other, speaker honoraria and patients’ fees: Roche, Novartis, Bristol Myers Squibb, Merck-EMD; Financial Interests, Personal, Other, speaker honorarium fees: Incyte , Pierre Fabre; Financial Interests, Personal, Other, patients’ fees: Merck Sharp & Dohme, Philiogen; Financial Interests, Personal, Other, steering committee honorarium fees: 4SC. B. Modi: Financial Interests, Personal, Advisory Board: Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, Merck; Financial Interests, Personal, Speaker’s Bureau: Regeneron Pharmaceuticals, Inc., Sanofi Genzyme. L. Dunn: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Research Grant: Regeneron, CUE Biopharma, Nektar pharmaceuticals, Replimune pharmaceuticals. L. Flatz: Financial Interests, Personal, Research Grant: Hookipa Pharma; Financial Interests, Personal, Advisory Board: Philogen. A. Hauschild: Financial Interests, Institutional, Research Grant: Amgen, Bristol Myers Squibb, Merck Sharp & Dohme/Merck, Pierre Fabre, Provectus, Roche , Novartis, erck Serono, Philogen , Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Other, speaker’s honoraria and consultancy fees: Amgen, Bristol Myers Squibb, Merck Sharp & Dohme/Merck, Pierre Fabre, Provectus, Roche , Novartis; Financial Interests, Personal, Other, consultancy fees: Merck Serono, Philogen , Regeneron Pharmaceuticals, Inc., OncoSec. S. Yoo: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Ownership Interest: Regeneron Pharmaceuticals, Inc. J. Booth: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Ownership Interest: Regeneron Pharmaceuticals, Inc. F. Seebach: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Ownership Interest: Regeneron Pharmaceuticals, Inc. I. Lowy: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Ownership Interest: Regeneron Pharmaceuticals, Inc. M.G. Fury: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Ownership Interest: Regeneron Pharmaceuticals, Inc. D. Rischin: Financial Interests, Institutional, Research Grant: Regeneron Pharmaceuticals, Inc., Sanofi, Kura Oncology, Roche, Merck Sharp & Dohme, Bristol Myers Squibb, GlaxoSmithKline , ALX Oncology; Non-Financial Interests, Personal, Other, uncompensated scientific committee and advisory board roles: Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc., Sanofi, GlaxoSmithKline. All other authors have declared no conflicts of interest.

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Melanoma and other skin tumours

818P - Phase II confirmatory study of cemiplimab (350mg IV Q3W) in patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC): Study 1540 Group 6

Presentation Number
818P
Speakers
  • Brett G. Hughes (Herston, Australia)
Date
Sat, 10.09.2022

Abstract

Background

While most patients (pts) diagnosed with CSCC are cured with local therapies, for the small percentage developing advanced CSCC the disease is life threatening with dismal prognosis. In a phase 1 (NCT02383212) and a pivotal phase 2 (NCT02760498) clinical trials, cemiplimab, an anti–programmed cell death receptor-1 [anti–PD-1], was the first systemic therapy to demonstrate significant antitumor activity in pts with advanced CSCC. Here, we report results from group 6 of the pivotal phase 2 trial, providing additional efficacy and safety data for cemiplimab monotherapy, 350 mg every 3 weeks (Q3W) up to 104 weeks, in patients with advanced CSCC.

Methods

Patients with advanced CSCC (metastatic [nodal or distant] or locally advanced) were treated with cemiplimab 350 mg intravenous (IV) Q3W for up to 108 weeks. The primary endpoint was objective response rate (ORR; complete response + partial response) per independent central review (ICR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS) by central and investigator review as well as safety and tolerability of cemiplimab.

Results

At data cut-off date of Oct 25 2021, 167 pts were enrolled, of which 165 pts received at least one dose of cemiplimab and were followed-up for a median of 8.71 months (range: 0.0 - 19.5). 5 of 167 pts received prior systemic therapies. Per ICR, ORR was 44.3% (74/167, 95% CI: 36.6%, 52.2%) with complete response in 5.4% (9/167), partial response in 38.9% (65/167), and DOR was not reached (95% CI: 13.0 months, not evaluable [NE]). Among treated patients, median PFS was 14.7 months (95% CI: 10.4, NE) and median OS was not reached (95% CI: 17.6 months, NE). The most common treatment-emergent adverse events (TEAEs) by any grade were fatigue (26.1%), diarrhoea and pruritus (each 21.2%), and nausea (17.0%). The most common grade ≥3 TEAEs were hypertension and pneumonia (each 3.6%), and general physical health deterioration (3.0%).

Conclusions

The group 6 primary analysis demonstrates a safety and efficacy profile that is consistent with that of the earlier groups of the study.

Clinical trial identification

NCT02760498.

Editorial acknowledgement

Medical writing support was provided by Osnat Ben-Shahar PhD from Regeneron.

Legal entity responsible for the study

Regeneron Pharmaceuticals, Inc. ((https://clinicaltrials.gov/ct2/show/NCT03088540 Sponsor: Regeneron Pharmaceuticals; Collaborator: Sanofi; Information provided by (Responsible Party): Regeneron Pharmaceuticals).

Funding

Regeneron Pharmaceuticals, Inc., and Sanofi.

Disclosure

B.G.M. Hughes: Financial Interests, Personal, Advisory Board: Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Roche, Sanofi, Eisai, Pfizer, AstraZeneca, Takeda; Financial Interests, Personal and Institutional, Research Grant: Amgen. J.J. Grob: Financial Interests, Personal, Advisory Board: BMS, MSD, Novartis, Roche, Amgen, Pierre-Fabre, Philogen, Pfizer, Merck, Sanofi; Financial Interests, Personal, Advisory Role: BMS. S.E. Bowyer: Financial Interests, Personal, Advisory Board: Ipsen, Sanofi, Lilly; Financial Interests, Personal, Other: Bristol Myers Squibb , MSD, Australia. F.L. Day: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Institutional, Other: Bristol Myers Squibb, AstraZeneca. R. Ladwa: Financial Interests, Personal, Other: MSD, BMS, AstraZeneca; Financial Interests, Personal, Advisory Role: AstraZeneca, Roche. B. Stein: Financial Interests, Personal, Stocks/Shares: Icon Group. E. Muñoz Couselo: Financial Interests, Personal, Advisory Board: Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche, Sanofi; Financial Interests, Personal, Other: Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche; Financial Interests, Personal and Institutional, Principal Investigator: Amgen, Bristol Myers Squibb, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche, Sanofi. N. Basset-Seguin: Financial Interests, Personal and Institutional, Invited Speaker: Regeneron/ Sanofi , Sun pharma , Galderma; Financial Interests, Personal and Institutional, Advisory Board: Regeneron/ Sanofi , Sun pharma , Galderma; Financial Interests, Personal and Institutional, Other: Regeneron/ Sanofi , Sun pharma , Galderma. A. Guminski: Financial Interests, Personal, Advisory Board: Regeneron, MSD, Pfizer; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Institutional, Research Grant: Sun Pharma ; Other, Institutional, Other: AZ. L. Mortier: Financial Interests, Personal, Advisory Board: BMS, MSD, Novartis, Pierre FabrE, Merck; Financial Interests, Personal, Principal Investigator: BMS, MSD, Novartis, Pierre Fabre, Merck. A. Hauschild: Financial Interests, Personal, Invited Speaker: Almirall, Amgen, BMS, Merck, Merck Serono, MSD/Merck, Novartis, Neracare, Philogen, Pierre Fabre, Provectus, Regeneron, Replimune, Roche, Sanofi, Sun Pharma; Financial Interests, Personal, Funding: Almirall, Amgen, BMS, Merck, Merck Serono, MSD/Merck, Novartis, Neracare, Philogen, Pierre Fabre, Provectus, Regeneron, Replimune, Roche, Sanofi, Sun Pharma; Financial Interests, Personal, Other: Almirall, Amgen, BMS, Merck, Merck Serono, MSD/Merck, Novartis, Neracare, Philogen, Pierre Fabre, Provectus, Regeneron, Replimune, Roche, Sanofi, Sun Pharma. M.R. Migden: Financial Interests, Personal, Advisory Role: Regeneron, Sanofi, Replimune, Sun pharmaceuticals. C. Schmults: Financial Interests, Personal, Funding: Castle Biosciences, Merck , Regeneron; Financial Interests, Personal, Research Grant: Castle Biosciences, Merck, Regeneron; Financial Interests, Personal, Other: Castle Biosciences, Regeneron , Sanofi, Merck; Non-Financial Interests, Personal, Member of the Board of Directors: American Society of Dermatologic Surgery; Non-Financial Interests, Personal, Advisory Board: International Society of Dermatologic Surgery; Non-Financial Interests, Personal, Officer: National Comprehensive Cancer Network. S. Yoo: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron . J. Booth: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron . F. Seebach: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron . I. Lowy: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron . M.G. Fury: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron . D. Rischin: Financial Interests, Institutional, Research Grant: Regeneron , Sanofi, Kura Oncology, Roche, Merck Sharp & Dohme, Bristol Myers Squibb, GlaxoSmithKline, ALX Oncology; Financial Interests, Institutional, Funding: Regeneron , Sanofi, Kura Oncology, Roche, Merck Sharp & Dohme, Bristol Myers Squibb, GlaxoSmithKline, ALX Oncology; Non-Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme, Regeneron, Sanofi, GlaxoSmithKline.

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Supportive care

1570P - A deep learning model for prediction of chemotherapy infusion related symptoms using continuous heart rate variability

Presentation Number
1570P
Speakers
  • Heekyung Ahn (Incheon, Korea, Republic of)
Date
Sat, 10.09.2022

Abstract

Background

We hypothesized chemotherapy infusion related reaction might be predictable according to continuous monitoring of heart rate recorded by a wearable device. In this study we propose a deep learning model that predicts patient level symptoms per minute during chemotherapy infusion.

Methods

We prospectively enrolled patients with cancer who will receive chemotherapy and at high risk for infusion related reaction. During chemotherapy infusion, 1 minute interval heart rate was recorded from a smart band and self-recorded symptom log was obtained. Patient's status at every minute was classified into 4 categories; normal, mild symptom without intervention, serious symptom which needed intervention, and patient's voluntary movement. The prediction model used the time windows of 120 minutes to predict infusion related symptoms over the current time. The model was trained 1500 epochs and we used the Adam optimizer with initial learning rate of 1e-3. We trained a multi-percentron layer based deep learning model. The losses were calculated by the cross-entropy. The model was validated using the holdout method with 20% of the datasts. The performance of the model was assessed with the receiver operating characteristic curves (AUROC) of 4 different events.

Results

We collected 1-minute interval heart rate record and patient's symptom logs during 4,716 minutes of 35 cycles of chemotherapy administration, from December 2021 to February 2022. The median age of enrolled patients was 60(range 35-85), and breast cancer(68.6%) was the most common diagnosis. Among 4,716 minutes, 277 (5.87%) minutes were labeled as non-normal status. Our model showed AUROC of 0.92 for normal status, 1.00 for mild symptoms, 0.82 for serious symptoms, and 0.97 for patient's voluntary movement. The proposed prediction model shows the 97.38% accuracy for 20% validation set.

Conclusions

This study showed that a deep learning model could recognize infusion related symptoms associated heart rate variability obtained by wearable device in real world patients receiving chemotherapy. Further studies for validation of predictive capability in a real time setting are warranted.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Colorectal cancer

381P - A tumor-informed, hybrid-capture based ctDNA assay for minimal residual disease (MRD) detection in colorectal cancer (CRC) patients after curative surgery

Presentation Number
381P
Speakers
  • Sae-Won Han (Seoul, Korea, Republic of)
Date
Sun, 11.09.2022

Abstract

Background

MRD detection using ctDNA analysis after curative treatment may help identify patients at higher risk of relapse and improve treatment outcomes by enabling personalized treatment. We have analyzed the clinical performance of a recently developed tissue-informed, hybrid-capture NGS-based ctDNA MRD assay in CRC.

Methods

Patients with stage II-III CRC treated with standard care surgery and/or adjuvant therapy with archived surgical tissue and preoperative and postoperative 3-week plasma samples were selected from a multi-center, prospective CRC cohort. For ctDNA MRD assay, AlphaLiquid Detect (IMBdx, Seoul, Korea) was used. It builds a personalized ctDNA panel for each patient including most of the variants meeting prespecified criteria found in tissue whole exome-sequencing data sequenced at ∼200-300x. Variants with clinical importance and high allele frequency are prioritized over potential germline variant sites and low mappability regions. A hybrid-capture based NGS data is generated for cell-free DNA at >100,000x to find ctDNA at a limit of detection <0.005%.

Results

A total of 71 patients (stage II/III 27(38.0%)/44(62.0%)) were successfully analyzed. 55 (77.5%) patients were treated with adjuvant therapy after surgery, and 3-year recurrence-free survival rate (RFS) was 67.5%. Personalized panels based on WES results included a median of 61 (6-166) mutations per patient. Using a cutoff value of 2 or more mutations for MRD positivity, 61/70 (87.1%) and 13/71 (18.3%) patients were confirmed to have ctDNA mutations exceeding the threshold from their preoperative and postoperative plasma samples, respectively. The postoperative MRD positivity was strongly associated with poor RFS (HR = 8.23, 95% CI 3.3 – 21, p < 0.001). A simulation study sub-selecting fewer variants in the pre-designed panels showed a substantial decrease in the sensitivity but minimal changes in specificity, demonstrating the strength of the assay targeting entire variants from each patient.

Conclusions

MRD positivity as determined by the tumor-informed, hybrid-capture based ctDNA assay showed a strong association with poor RFS in CRC.

Legal entity responsible for the study

The authors.

Funding

IMBdx.

Disclosure

S. Heo: Financial Interests, Personal, Full or part-time Employment: IMBdx. Y. Lim: Financial Interests, Personal, Full or part-time Employment: IMBdx, Lunit Inc.. W. Lee: Financial Interests, Personal, Full or part-time Employment: IMBdx. H. Kim: Financial Interests, Personal, Full or part-time Employment: IMBdx. S.Y. Kim: Financial Interests, Personal, Full or part-time Employment: IMBdx. D. Bang: Financial Interests, Personal, Stocks/Shares: IMBdx. T. Kim: Financial Interests, Personal, Stocks/Shares: IMBdx. All other authors have declared no conflicts of interest.

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Gynaecological cancers

551P - Genomic DNA analysis of cervical smear samples of endometrial cancer with next-generation sequencing: A prospective study

Presentation Number
551P
Speakers
  • Namsoo Kim (Seoul, Korea, Republic of)
Date
Sun, 11.09.2022

Abstract

Background

Tumor marker, CT, MRI, and cervical smear were conventional methods for early diagnosis and predict prognosis in endometrial cancer, but they still had limitations. Cervical smear samples, which are easy to obtain, and reflect the tumor environment, are sequenced in this study.

Methods

Patients who underwent endometrial surgery were prospectively enrolled since January 2021. Cervical smear samples were obtained preoperatively via vaginal sampling. Matched blood samples were obtained simultaneously. Tumor genomic DNA (gDNA) and cell-free DNA were extracted and analyzed with a custom panel that covers 100 endometrial cancer-related genes. Prepared libraries were sequenced using NovaSeq 6000 System (Illumina) and analyzed using PiSeq analysis (Dxome).

Results

Cervical smear samples were obtained from 101 patients, including 76 cancer patients with predominantly early-stage cancer (i.e., 40 stage IA patients and 17 stage III or IV patients) and 25 non-cancer patients. Overall, cervical swab-based gDNA detected cancer with a sensitivity of 66% and specificity of 96%. Investigation of matched blood and matched PAP smear among endometrial cancer patients showed that the detection rate of cervical swab-based gDNA was higher than either of the two modalities. Also, we identified patients effectively with loss of MSH2 or MSH6 and aberrant p53 expression based on immunohistochemistry. Genomic landscape analysis identified PTEN, PIK3CA, TP53, ARID1A, KRAS, and CTNNB1 as the most frequently altered genes. There were co-occurring genes, such as PTEN with ARID1A and PIK3CA, and TP53 was captured exclusively with CTNNB1, ARD1A, and PTEN. 50 patients were classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer: MMRd (n=6, 12%), POLE (n=3, 6%), p53 abnormal (n=10, 20%) and p53 wildtype (n=31, 62%). CTNNB1 mutation occurred in 8 patients in the p53 wildtype group.

Conclusions

Cervical swab-based gDNA showed moderate sensitivity and high specificity, with an improved detection rate compared to either whole blood ctDNA or conventional PAP smear. Furthermore, it allowed patients to be classified according to ProMisE classification, having both predictive and prognostic implications.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Gynaecological cancers

588P - Prognostic value of circulating tumor DNA (ctDNA) in ovarian cancer

Presentation Number
588P
Speakers
  • Jinho Heo (Seoul, Korea, Republic of)
Date
Sun, 11.09.2022

Abstract

Background

Effective detection of ovarian cancer progression and recurrence is crucial in improving patient prognosis. Existing tests based on biomarker (CA-125) and radiological imaging are insufficient for the early detection of recurrent ovarian cancer. This study aimed to assess the feasibility of using circulating tumor DNA (ctDNA) as a biomarker for disease progression in ovarian cancer patients undergoing debulking surgery followed by adjuvant therapy.

Methods

10 mL of blood samples were collected from patient with ovarian carcinoma at Severance Hospital, Seoul, Korea (Oct 2019–Feb 2022). Samples were collected at baseline just prior to surgery and every three months thereafter. Conventional post operative monitoring was performed using CA125, HE4, MRI, and PET-CT. Custom target gene panel targeting nine genes (TP53, BRCA1, BRCA2, ARID1A, CCNE1, KRAS, MYC, PIK3CA and PTEN). Next-generation sequencing was done with the NextSeq System (Illumina, USA). Data analysis was performed using the custom pipeline (Dxome, Korea). Retrospective chart review was done to obtain relevant clinical information.

Results

We analyzed a total of 703 whole blood samples from 243 patients, including 170 patients with carcinoma (high or low-grade serous, mucinous, clear cell, or endometrioid) and 73 patients with benign/borderline ovarian disease. 71.2% (121/170) carcinoma patients were identified with tier I/II (pathogenic) somatic mutations from preoperative samples at baseline. No pathogenic mutations were identified in benign/borderline tumor patients (0/73). Of the 38 progressive patients with baseline ctDNA mutation, 92.1% (35/38) patients were identified with the same list of mutations at the baseline. In these 35 patients, ctDNA enabled early detection of future progression by an average of 50.9 days (maximum of 267 days) than the conventional diagnostic methods. Based on 6 months follow up ctDNA analysis, persistent elevated group showed a shorter median survival compared with zero conversion group (7.9 vs 31.2 months; P < 0.001).

Conclusions

Our analysis suggests that ctDNA-based surveillance may serve an important role in the early detection of disease progression in ovarian cancer, allowing prognostic stratification and prompt clinical decision making with progression.

Legal entity responsible for the study

The authors.

Funding

DXOME CO., LTD.

Disclosure

S. Lee: Financial Interests, Personal and Institutional, Member of the Board of Directors: DXOME CO., LTD. J.R. Choi: Financial Interests, Personal and Institutional, Member of the Board of Directors: DXOME CO., LTD. All other authors have declared no conflicts of interest.

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