ESMO Supporter 2018

Found 34 Presentations For Request "KEYNOTE-057"

Proffered paper session - Genitourinary tumours, non prostate Proffered Paper session

864O - Pembrolizumab for High-Risk (HR) Non–Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guérin (BCG): Phase 2 KEYNOTE-057 Trial

Presentation Number
864O
Lecture Time
09:54 - 10:06
Speakers
  • Ronald De Wit (Rotterdam, NL)
Location
Hall A1 - Room 17, ICM München, Munich, Germany
Date
20.10.2018
Time
09:15 - 10:45

Abstract

Background

Activation of the PD-1 pathway has been implicated in resistance to BCG therapy. Pembrolizumab (pembro), a checkpoint inhibitor with significant activity in patients (pts) with metastatic urothelial carcinoma, was evaluated in this population. KEYNOTE-057 (NCT02625961) is a single-arm phase 2 study of the efficacy and safety of pembro in pts with HR, BCG-unresponsive NMIBC. Preliminary results for cohort A (carcinoma in situ [CIS] or CIS plus papillary tumor) are presented.

Methods

Eligible pts had histologically confirmed high-grade BCG-unresponsive NMIBC, including CIS alone or combination of CIS and papillary disease (cohort A), had been treated with adequate BCG therapy (at least 5/6 induction instillations and 2/3 maintenance therapy instillations), and were unable or unwilling to undergo radical cystectomy. Pts received pembro 200 mg Q3W for 24 mo or until recurrence, progression, or unacceptable toxicity. The primary end point for cohort A was complete response (CR); key secondary end points were safety and duration of response. Pts found to have HR NMIBC or progressive disease during treatment were required to discontinue.

Results

At the time of data cutoff, 101 pts were enrolled in cohort A. Median follow-up was 9.4 mo (range 0.2-21.2). At mo 3, CR rate by central assessment was 36.5% (95% CI 26.3-47.6) in 85 evaluable pts. Among the 31 pts with CR at mo 3, median duration of CR was 8.1 mo (range 0+ to 13.7+). Estimated proportion of pts with response duration ≥6 mo was 85.6%. Treatment-related adverse events (AEs) occurred in 54 pts (55.7%); most common (≥5%) were diarrhea (9.3%), pruritus (9.3%), fatigue (7.2%), hypothyroidism (5.2%), maculopapular rash (5.2%), and arthralgia (5.2%). Treatment-related grade 3-5 AEs occurred in 11 pts (11.3%); 1 death was considered treatment related. Immune-mediated AEs occurred in 15 pts (15.5%) and were grade 3/4 in 2 pts (2.1%).

Conclusions

Pembro exhibits encouraging antitumor activity in pts with HR and BCG-unresponsive NMIBC with CIS. The safety profile of pembro in this pt population is consistent with that of previous studies. KEYNOTE-057 is ongoing.

Clinical trial identification

NCT02625961.

Legal entity responsible for the study

Merck & Co., Inc.

Funding

Merck & Co., Inc.

Editorial Acknowledgement

Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

R. de Wit: Consultancy: Sanofi, Merck, Roche; Speaker fees: Sanofi, Merck. G.S. Kulkarni: Advisory board member: Ferring, Janssen, Astellas, Amgen, Bayer, Theralase. Research funding: Biosyent. Honoraria: Abbvie, TerSera. Travel expenses, including accommodations: Abbvie, Sanofi, TerSera, Bayer. E.A. Singer: Research funding: Astellas/Medivation. L. Krieger: Advisory board member: Bayer, AstraZeneca, BMS, MSD, Roche, Janssen, Ipsen, Novartis, Pfizer, Astellas Speakers' bureau: MSD, Bayer, BMS, Ipsen Honoraria: Bayer, Ipsen, BMS, Novartis, Janssen, Astellas, MSD Travel expenses: Astella, Ipsen, Roche, MSD. P. Grivas: Honoraria: Merck & Co.; Genentech; Bristol-Myers Squibb; AstraZeneca; EMD Serono; Clovis Oncology; Seattle Genetics; Foundation Medicine; Driver Inc. D. Bajorin: Advisory board member: Merck, Genentech, Bristol Myers Squibb, Urogen, Novartis; Research funding: Merck, Novartis. A. Kamat: Research funding: FKD, Merck, Telesta, Adolor. Honoraria TMC Innovation, Merck, BMS, Arquer, MDxHealth, Photocure, Theralase, Cepheid, Medac, Asieris, Pfizer, Astra Zeneca. E. Kapadia, K. Nam, T. Frenkl: Employee and stockholder: Merck & Co., Inc. A. Balar: Advisory board member: Genentech, Merck, Incyte, AstraZeneca, Seattle Genetics, Pfizer/EMD Serono. Research funding: Genentech, Merck, AstraZeneca. Honoraria: Merck, AstraZeneca, Genentech. All other authors have declared no conflicts of interest.

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Poster Discussion session - NSCLC, metastatic 2 Poster Discussion session

LBA62 - Health-related quality of life (HRQoL) for pembrolizumab or placebo plus carboplatin and paclitaxel or nab-paclitaxel in patients with metastatic squamous NSCLC: data from KEYNOTE-407

Presentation Number
LBA62
Lecture Time
16:45 - 16:45
Speakers
  • Julien Mazieres (Toulouse, FR)
Location
ICM - Room 13, ICM München, Munich, Germany
Date
21.10.2018
Time
16:45 - 17:45

Abstract

Background

In the randomized, double-blind, phase 3 KEYNOTE-407 study, pembrolizumab (pembro) plus carboplatin and paclitaxel or nab-paclitaxel improved OS, PFS, and ORR and had a manageable safety profile compared with placebo (pbo) plus carboplatin and paclitaxel or nab-paclitaxel as first-line therapy for patients with metastatic squamous NSCLC. Patient-reported outcomes (PROs) were a prespecified exploratory endpoint of KEYNOTE-407 (NCT02775435).

Methods

559 patients with previously untreated stage IV squamous NSCLC, ECOG PS 0–1, and measurable disease per RECIST v1.1 were randomized 1:1 to receive 4 cycles of pembro 200 mg Q3W or pbo Q3W plus carboplatin AUC 6 and paclitaxel 200 mg/m2 Q3W or nab-paclitaxel 100 mg/m2 QW, followed by pembro or pbo monotherapy for up to 35 cycles total. The EORTC QLQ-C30 and QLQ-LC13 were administered at cycles 1–7, then every 3 cycles up to week 48. Prespecified key PROs were change from baseline to weeks 9 and 18 in the QLQ-C30 global health status (GHS)/quality of life (QoL) score and time to 10-point deterioration in the composite endpoint of cough, chest pain, or dyspnea. P values are 2-sided and nominal.

Results

PRO analyses included 554 and 553 patients who completed ≥1 QLQ-C30 or ≥1 QLQ-LC13 assessment, respectively, and received ≥1 administration of study treatment. Compliance rates were similar between the groups and instruments (baseline, ~93%–94%; week 9, ~84%; week 18, ~87%). Mean QLQ-C30 GHS/QoL baseline scores were 63.9 in the pembro combination group and 62.7 in the pbo combination group. At weeks 9 and 18, the mean score for QLQ-C30 GHS/QoL improved from baseline in the pembro combination group and decreased in the pbo combination group (least squares mean difference between groups: week 9, 3.6 points [95% CI, 0.3–6.9], P=0.0337; week 18, 4.9 points [95% CI, 1.4–8.3], P=0.0060). Median time to deterioration in the composite endpoint of cough, chest pain, or dyspnea was not reached in either group (HR, 0.79 [95% CI, 0.58–1.06]; P=0.125).

Conclusions

Addition of pembro to chemotherapy maintained or improved HRQoL measurements over chemotherapy alone, supporting its use as first-line therapy for metastatic squamous NSCLC.

Clinical trial identification

ClinicalTrials.gov number NCT02775435, originally posted May 17, 2016

Editorial Acknowledgement

Medical writing and editorial assistance was provided by C4 MedSolutions, LLC (Yardley, PA), a CHC Group company. This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology Poster Display session

785TiP - Phase 3 KEYNOTE-590 Study of Chemotherapy + Pembrolizumab Versus Chemotherapy + Placebo as First-Line Therapy for Patients (Pts) With Advanced Esophageal or Esophagogastric Junction (E/EGJ) Cancer

Presentation Number
785TiP
Lecture Time
12:45 - 12:45
Speakers
  • Ken Kato (Tokyo, JP)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
21.10.2018
Time
12:45 - 13:45

Abstract

Background

In the phase 1b KEYNOTE-028 study, pembrolizumab monotherapy demonstrated manageable safety and durable antitumor activity in heavily pretreated pts with PD-L1–positive advanced esophageal carcinoma. KEYNOTE-590 (ClinicalTrials.gov, NCT03189719) is a phase 3, randomized, double-blind, multicenter study of cisplatin and 5-fluorouracil plus pembrolizumab vs cisplatin and 5-fluorouracil plus placebo in pts with previously untreated advanced E/EGJ carcinoma.

Trial design

Eligibility criteria are age ≥18 years; locally advanced unresectable or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or metastatic Siewert type 1 adenocarcinoma of the EGJ; no prior therapy for advanced disease; measurable disease per RECIST v1.1; ECOG performance status 0/1; adequate organ function; no autoimmune disease; no active infection; and provision of tissue sample for evaluation of PD-L1 expression and gene expression profiling. Pts will be randomly assigned 1:1 to receive cisplatin 80 mg/m2 IV every 3 weeks (Q3W) (capped at 6 doses) plus 5-fluorouracil 800 mg/m2 continuous IV on days 1-5 Q3W plus pembrolizumab 200 mg IV Q3W or cisplatin 80 mg/m2 IV Q3W (capped at 6 doses) plus 5-fluorouracil 800 mg/m2 continuous IV on days 1-5 Q3W plus placebo Q3W IV. Pts will continue treatment for up to 2 years. Crossover from one treatment arm to another is not permitted. Coprimary end points are overall survival and progression-free survival per RECIST v1.1 by blinded independent central review in all pts and in pts with PD-L1–positive tumor expression (combined positive score ≥10%). Secondary end points include objective response rate per RECIST v1.1, duration of response, safety, and health-related quality of life. Response will be assessed using computed tomography (preferred) or magnetic resonance imaging every 9 weeks by central imaging review per RECIST v1.1. Adverse events (AEs) will be graded per NCI CTCAE v4.0 and monitored for at least 30 days (90 days for serious AEs) after the last dose of study treatment. Pts will be followed up for survival status. Planned enrollment is approximately 700 pts.

Clinical trial identification

NCT03189719. The study start date was July 25, 2017.

Legal entity responsible for the study

Merck & Co., Inc.

Funding

Merck & Co., Inc.

Editorial Acknowledgement

Medical writing and/or editorial assistance was provided by Sarita Shaevitz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

K. Kato: Advisory board member: MSD, Ono, Beigene; Research funding: MSD, Ono, Shionogi, Merck Serono M.A. Shah: Research funding: Merck, Roche, Boston Biomedical P.C. Enzinger: Advisory board member: Merck, Astellas, Five Prime, Lilly, Celgene, Beigene J. Bennouna: Advisory board member: Roche, Boehringer Ingelheim, AstraZeneca, Shire, MSD; Honoraria: Roche, Boehringer Ingelheim, AstraZeneca, Shire, MSD. A. Adenis: Advisory board member: Bayer, BMS, Servier; Research funding: Bayer, BMS, Merck, Sanofi, Pfizer; Honoraria: Bayer, BMS, Sanofi; Travel expenses: BMS, Merck, Bayer. J-M. Sun: Advisory board member: Boehringer Ingelheim, Research funding: AstraZeneca. B.C. Cho: Advisory board member: AstraZeneca, Roche, Boehringer Ingelheim, Yuhan, BMS, MSD, Novartis Speakers' bureau: AstraZeneca, BMS, MSD, Novartis; Research funding: Bayer, AstraZeneca, Yuhan, Novartis; Honoraria: AstraZeneca, Roche, Boehringer Ingelheim, Yuhan, BMS, MSD, Novartis. M. Ozguroglu: Advisory board member: Astellas, Janssen Honoraria: Janssen. T. Kojima: Honoraria: Oncolys Biopharma Other-Patents, Royalties; Other Intellectual Property: Ono Pharmaceutical, MSD, Shionogi Pharma, Oncolys BioPharma, Astellas Amgen BioPharama. V. Kostorov, T. Doi: Advisory board member: Novartis, MSD, Lilly Japan, Chugai Pharma, Kyowa Hakko Kirin, Daiichi Sankyo, Amgen Research funding: Taiho, Novartis, Merck Serono, Astellas Pharma, MSD, Janssen, Boehringer Ingelheim, Takeda, Pfizer, Lilly, Sumitomo Group, Chugai Pharma, Bayer, Kyowa Hakko Kirin, Daiichi Sankyo, Celgene. Y. Zhu, P. Bhagia: Employee: Merck. S. Shah: Employee, Stock owner: Merck. All other authors have declared no conflicts of interest.

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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology Poster Display session

1122TiP - Pembrolizumab in Patients With Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma (cSCC): The Phase 2 KEYNOTE-629 Study

Presentation Number
1122TiP
Lecture Time
12:45 - 12:45
Speakers
  • Lisa F. Licitra (Milan, IT)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
21.10.2018
Time
12:45 - 13:45

Abstract

Background

There are no approved treatments or standard of care for recurrent or metastatic cSCC. Effectiveness of common therapies for cSCC is limited. Regimens effective for SCC of the head and neck (HNSCC) may also be effective for cSCC. Pembrolizumab is a programmed death 1 (PD-1) inhibitor that directly blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Evidence of pembrolizumab efficacy and safety has been shown in patients with recurrent or metastatic HNSCC in the phase 1b KEYNOTE-012 study. The single-arm, open-label phase 2 KEYNOTE-629 trial will be conducted to evaluate the efficacy and tolerability of pembrolizumab in patients with previously treated recurrent or metastatic cSCC (NCT03284424).

Trial design

Patients will be given pembrolizumab 200 mg every 3 weeks by intravenous infusion, continued for 35 doses (∼2 years) or until disease progression, unacceptable toxicity, intercurrent illness, nonadherence, or investigator or patient decision to withdraw. Radiographic imaging will be performed every 6 weeks for year 1 and every 9 weeks thereafter. Adverse events will be monitored and graded per National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Key inclusion criteria are age ≥18 years; histologically confirmed cSCC as the primary site of malignancy; metastatic disease or locally recurrent disease not curable by surgery or radiation; measurable disease per RECIST v1.1; and Eastern Cooperative Oncology Group performance status 0/1. There is no requirement for prior chemotherapy or biological systemic treatment for incurably recurrent/metastatic disease. Primary end point is objective response rate per RECIST v1.1 assessed by blinded independent central review. Secondary end points are duration of response, disease control rate (complete or partial response or stable disease for ≥12 weeks), progression-free survival per RECIST v1.1, overall survival, safety, and tolerability. Pharmacokinetics, biomarkers, and health-related quality of life will be evaluated as exploratory end points. Recruitment is ongoing in 10 countries and will continue until 100 patients are enrolled.

Clinical trial identification

NCT03284424. Trial initiated September 15, 2017.

Legal entity responsible for the study

Merck & Co, Inc.

Funding

Merck & Co, Inc.

Editorial Acknowledgement

Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck & Co, Inc, Kenilworth, NJ, USA.

Disclosure

L.F. Licitra: Consultant: Eisai, Amgen, Boehringer Ingelheim, Debiopharm Gropu, AstraZeneca, Sobi, Novartis, Bayer, Merck, Merck Serono, Roche, BMS; Research funding: Eisai, Amgen, Merck Serono, Boehringer Ingelheim, AstraZeneca, Novartis, Roche, Merck. L.L. Siu: Consultant: Merck, AstraZeneca/Medimmune, MorphoSys, Symphogen; Research funding: BMS, Genentech/Roche, GlaxoSmithKline, Merck, Novartis, Pfizer, Medimmune, AstraZeneca, Boehringer Ingelheim, Bayer, Amgen, Symphogen, Astellas. E.E.W. Cohen: Consultant: Merck, BMS, AstraZeneca, Human Longevity, Inc, Pfizer, EMD Serono. P. Zhang: Employment and travel: Merck, B. Gumuscu, R. Swaby: Employment and stock: Merck. K. Harrington: Honoraria, Consultant, Speakers Bureau: Amgen, AstraZeneca, Merck, Merck Sharp & Dohme, Pfizer, BMS; Research funding: AstraZeneca, Merck; Travel: Merck Sharp & Dohme.

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Proffered paper session - Melanoma and other skin tumours Proffered Paper session

1244O - KEYNOTE-022 Part 3: Phase 2 Randomized Study of 1L Dabrafenib (D) and Trametinib (T) Plus Pembrolizumab (Pembro) or Placebo (PBO) for BRAF-Mutant Advanced Melanoma

Presentation Number
1244O
Lecture Time
10:15 - 10:30
Speakers
  • Paolo A. Ascierto (Napoli, IT)
Location
ICM - Room 1, ICM München, Munich, Germany
Date
22.10.2018
Time
09:15 - 10:45

Abstract

Background

Pembro + D + T had promising antitumor activity and acceptable tolerability in phase 1 of KEYNOTE-022 (NCT02130466).

Methods

In the double-blind phase 2 part of KEYNOTE-022, pts with treatment (tx)-naive BRAFV600E/K-mutant stage III/IV melanoma were randomly assigned (stratified by ECOG PS [0/1)]; LDH level [>1.1 vs ≤ 1.1× ULN]) to pembro 2 mg/kg Q3W + D 150 mg BID + T 2 mg QD or PBO + D + T. Strata with ECOG PS 1 and either LDH level were combined due to small numbers. Primary end point was PFS. Significance requirements to reject null hypothesis at 1-sided 0.025 type I error: ∼74 PFS events for 80% power; observed HR ≤ 0.62. Additional end points included ORR, DOR, TTR, and OS. Data cutoff: Feb 15, 2018.

Results

Of 60 pts in each arm, most baseline characteristics were balanced (stage IV disease, 98% in pembro + D + T vs 95% in PBO + D + T; ECOG PS 0, 80% both; LDH >1.1× ULN, 45% vs 43%). Median follow-up for both arms was 9.6 mo (range 2.7-23.4). 67% vs 70% received ≥12 mo tx. Median PFS was 16.0 mo (95% CI 8.6-21.5) with pembro + D + T vs 10.3 mo (95% CI 7.0-15.6) with PBO + D + T; HR, 0.66; P = 0.04287; 12-mo PFS rates were 59% vs 45%. ORR was 63% vs 72%; CR rates were 18% vs 13%. Median TTR was 2.8 mo in each arm; median DOR was 18.7 mo (range 1.9+ to 22.1) vs 12.5 (2.1-19.5+). More patients (60%) on pembro + D + T had responses lasting ≥18 mo vs PBO + D + T (28%). OS rates at 12 mo were 80% vs 73%. Any grade (G) treatment-related AEs (TRAEs) occurred in 95% vs 93% and G3-5 TRAEs occurred in 58% vs 27% of pts. G3-5 TRAEs occurring in ≥ 5% of pts were pyrexia (10% vs 3%), increased ALT (7% vs 5%), increased AST (8% vs 5%), increased GGT (7% vs 5%), rash (5% vs 2%), and neutropenia (2% vs 5%). 40% vs 20% of pts discontinued any of the 3 study tx due to TRAEs, and 1 pt died due to a TRAE (pneumonitis) in the pembro + D + T arm. Immune-mediated AEs occurred in 43% vs 13% of pts, most commonly pneumonitis (15% vs 2%), hypothyroidism (8% vs 2%), skin disorders (7% vs 2%), hyperthyroidism (5% vs 0%), and uveitis (5% vs 3%); most resolved with tx discontinuation/modification.

Conclusions

Pembro + D + T vs PBO + D + T demonstrated numerically longer PFS and DOR and a higher rate of G3-5 TRAEs in pts with tx-naive BRAFV600E/K-mutant advanced melanoma.

Clinical trial identification

NCT02130466.

Legal entity responsible for the study

Merck & Co., Inc.

Funding

Merck & Co., Inc.

Editorial Acknowledgement

Medical writing and/or editorial assistance was provided by Doyel Mitra, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

P.A. Ascierto: Advisory board member: BMS, Roche-Genentech, MSD, Array, Novartis, Amgen, Merck Serono, Pierre Fabre, Incyte, Genmab, Newlink Genetics, Medimmune, Syndax, AstraZeneca; Research funding: BMS, Roche-Genentech, Array. P.F. Ferrucci: Advisory board member: BMS, Novartis, MSD; Research funding: BMS, MSD; Honoraria, travel expenses, accommodations: BMS, Novartis, MSD, Roche. R. Stephens: Honoraria, travel expenses: MSD NZ. M. Del Vecchio: Consultant, advisor, research funds: Bristol-Myers Squibb, Roche-Genentech, GlaxoSmithKline, Merck Sharp and Dohme. V. Atkinson: Advisory board member: BMS, MSD, Novartis, Merck Serono, Pierre Fabre; Speakers’ bureau: BMS, MSD, Novartis, Roche; Honoraria: BMS, MSD, Novartis; Travel expenses: BMS, MSD. H. Schmidt: Advisory board member: BMS, MSD, Incyte, Roche; Speakers’ bureau: BMS, Novartis; Research funding: MSD; BMS. J. Schachter: Honoraria, consultant/advisory, travel, accomodations, expenses: BMS, MSD. P. Queirolo: Advisory board member, speakers' bureau, gonoraria, travel expenses, accommodations: BMS, Roche, Novartis, MSD. G.V. Long, A.M. Di Giacomo: Advisory board member: Incyte, GSK, Pierre Fabre; Honoraria: BMS, Roche, MSD; Travel expenses, including accommodations: BMS, Roche. I. Svane: Honoraria/Consulting fees: Roche, Novartis, Merck, MSD, Celgene, Incyte, Pfizer, BMS, AstraZeneca, TILT Bio, IO Biotech; Stock (co-founder): IO Biotech. M. Lotem: Advisory board member: Merck; Honoraria: Merck, BMS; Travel expenses, accommodations: Merck, BMS, Novartis. G. Bar-Sela: Research funding: Merck. B.P. Mookerjee: Employee: Novartis; Stock: Novartis, GSK, AstraZeneca. R. Ghori, N. Ibrahim, B. Homet Moreno: Employee: Merck & Co., Inc. A. Ribas: Stock ownership: Lutris, PACT, Tango; Advisory board member: Advaxis, Arcus, BioncoTech, Compugen, CytomX, Five Prime, FLX-Bio, ImaginAb, Isoplexis, Kite-Gilead, Rgenix; Honoraria: Amgen, BMS, Chugai, Genentech, Merck, Novartis, Roche. All other authors have declared no conflicts of interest.

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Poster Discussion session - Gynaecological cancers Poster Discussion session

LBA36 - Association of PD-L1 Expression and Gene Expression Profiling With Clinical Response to Pembrolizumab in Patients With Advanced Recurrent Ovarian Cancer: Results From the Phase 2 KEYNOTE-100 Study

Presentation Number
LBA36
Lecture Time
09:37 - 09:37
Speakers
  • Jonathan A. Ledermann (London, GB)
Location
ICM - Room 13, ICM München, Munich, Germany
Date
20.10.2018
Time
09:15 - 10:45

Abstract

Background

KEYNOTE-100 (NCT02674061) showed pembrolizumab (pembro) has clinical activity in patients (pts) with advanced ovarian cancer (AOC), and PD-L1 expression (combined positive score [CPS] ≥10) was associated with response. Other biomarkers possibly associated with response were evaluated.

Methods

Key inclusion criteria included epithelial ovarian, fallopian tube, or primary peritoneal cancer, confirmed recurrence following front-line platinum-based therapy, ECOG PS 0/1, and tumor sample. Pts received pembro 200 mg Q3W IV for 2 y or until progression, death, unacceptable toxicity, or consent withdrawal. Whole exome sequencing of paired tumor and normal samples determined homologous recombination deficiency genomic scar (HRD) and BRCA1/2 mutation status (BRCA) using standard algorithms. Associations of response with T-cell-inflamed 18-gene expression profile (T-cell-GEP) score, HRD, BRCA, and microsatellite instability-high (MSI-H) were evaluated.

Results

T-cell-GEP, BRCA, and HRD data were available from the first 100 pts enrolled, while MSI-H was from the entire study population (n=319). Among patients with T-cell-GEP, distribution of GEP scores was significantly higher in responders than nonresponders (1-sided p=0.03 from Wilcoxon rank sum test; n=83). 7/83 pts (8.4%) had a response. In pts with available PD-L1 CPS and GEP (n=79; Spearman’s correlation ρ=0.57), the area under the receiver characteristic curves for CPS and T-cell-GEP were numerically similar (0.73 vs 0.72, respectively). No statistically significant differences were observed with HRD values among responders and nonresponders (1-sided p=0.29; n=71). No association between BRCA status (n=11 mutant; n=60 wild type) and response was observed (1-sided p=0.65). 6/71 pts (8.5%) in this population had a response. Of 319 paired samples tested for MSI-H, all were MSS.

Conclusions

In addition to PD-L1 CPS, T-cell-GEP was associated with a response to pembro monotherapy for treatment of AOC in a single-arm setting, while HRD biomarkers (HRD, BRCA) were not found to be associated with response.

Clinical trial identification

NCT02674061; release date, February 25, 2016

Editorial Acknowledgement

Medical writing assistance was provided by Christine McCrary Sisk, an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and by Matthew Grzywacz, ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

871P - KEYNOTE-427 Cohort A: Pembrolizumab Monotherapy as First-Line Therapy in Advanced Clear Cell Renal Cell Carcinoma (ccRCC)

Presentation Number
871P
Lecture Time
13:05 - 13:05
Speakers
  • Frede Donskov (Aarhus, DK)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

KEYNOTE-427 (NCT02853344) is a single-arm, open-label, 2-cohort, phase 2 study to evaluate efficacy and safety of the PD-1 inhibitor pembrolizumab (pembro) as first-line monotherapy in advanced ccRCC and non-ccRCC. Results from the ccRCC cohort (cohort A) are presented.

Methods

Pembro 200 mg was administered intravenously Q3W for 2 y or until confirmed progressive disease, unacceptable toxicity, or patient (pt) decision to withdraw. Pts with histologically confirmed advanced ccRCC who had received no prior systemic therapy were eligible. Additional key eligibility criteria: measurable disease (RECIST v1.1, independent central review [ICR]) and Karnofsky performance status ≥70%. Primary end point: ORR per RECIST v1.1, by ICR. Additional end points: DOR, PFS, OS, safety, and biomarkers associated with response.

Results

At data cutoff (Oct 6, 2017), median (range) follow-up was 7.2 (0.9-11.7) mo. 110 pts enrolled; 107 were included in efficacy analysis (opportunity for ≥1 postbaseline assessment). Treatment was ongoing for 64 (58.2%) pts. Median age (range) was 64 (29-87) years; 78% were male. 37.3%, 47.3%, and 15.5% had IMDC risk categories of favorable, intermediate, and poor, respectively. Confirmed ORR by ICR was 33.6% (n = 36; 95% CI 24.8-43.4) with 1 complete response (0.9%) and 35 (32.7%) partial responses. 39 (36.4%) had stable disease. ORR for pts with favorable or intermediate/poor risk IMDC was 27.5% and 37.3%, respectively. Median DOR was not reached (range 1.4+ to 8.2+ mo); 86.1% of responders had response ≥3 months. Median PFS was 6.9 (95% CI 5.1-NR) mo; PFS rate at 6 mo was 53.6%. OS rates at 3 and 6 mo were 97.2% and 92.4%, respectively. 73.6% of pts had a treatment-related adverse event (AE); most common (≥10%) were fatigue (23.6%), pruritus (21.8%), diarrhea (16.4%), rash (12.7%), and arthralgia (11.8%). 18.2% experienced a grade 3-5 treatment-related AE; 1 pt had grade 5 pneumonitis.

Conclusions

Pembro monotherapy showed encouraging efficacy and acceptable tolerability in pts with advanced ccRCC. Updated analyses will be presented using additional follow-up data and outcomes by PDL-1 status and other relevant subgroups.

Clinical trial identification

NCT02853344. Trial initiated August 2, 2016.

Legal entity responsible for the study

Merck & Co., Inc.

Funding

Merck & Co., Inc.

Editorial Acknowledgement

Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

F. Donskov: Research funding: Pfizer, Novartis, Ipsen. B.Y. Alekseev: Research funding: Merck. J.M.G. Larkin: Research funding: BMS, MSD, Novartis, Pfizer; Honoraria: BMS, MSD, GSK, Pfizer, Novartis, EUSA pharma, Roche/Genentech, Secarna, Pierre Fabre, Eisai, Kymab; Travel expenses, including accommodations: BMS, MSD, GSK, Pfizer, Novartis, EUSA Pharma, Roche/Genentech, Secarna, Pierre Fabre, Eisai, Kymab; Consultancy: BMS, MSD, GSK, Pfizer, Novartis, EUSA Pharma, Roche/Genentech, Secarna, Pierre Fabre, Eisai, Kymab. S.S. Tykodi: Advisory board: Calithera Biosciences, Prometheus Laboratories; Research funding (to institution): Merck, Bristol-Myers Squibb, Peloton Therapeutics, Nektar Therapeutics, Calithera Biosciences, Jounce Therapeutics, Pfizer, Genentech, Prometheus Laboratories, Argos Therapeutics. P.F. Geertsen: Research funding: Novartis; Travel expenses: Novartis, BMS, Pfizer. T. Alonso Gordoa: Research funding: Roche; Honoraria: Pfizer, Janssen, Astellas, Novartis, Roche, Sanofi. R. Kloss Silverman, R.F. Perini: Employment: Merck & Co., Inc. C. Schloss: Employment and stock ownership: Merck & Co., Inc. M.B. Atkins: Consulting: BMS, Merck, Novartis, Genentech/Roche, Pfizer, Exelixis, Eisai, AstraZeneca, Array; Research funding: BMS, Novartis, Genentech/Roche; Board of directors or advisory committees: Novartis, Merck, Pfizer. All other authors have declared no conflicts of interest.

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Poster discussion session - Immunotherapy of cancer 1 Poster Discussion session

LBA40 - Phase 1b KEYNOTE-200. A study of an intravenously delivered oncolytic virus, Coxsackievirus A21 in combination with pembrolizumab in advanced NSCLC and bladder cancer patients

Presentation Number
LBA40
Lecture Time
17:15 - 17:15
Speakers
  • Charles M. Rudin (New York, US)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
20.10.2018
Time
16:45 - 17:45

Abstract

Background

Coxsackievirus A21 (CVA21, CAVATAK) is a naturally occurring ICAM-1 targeted oncolytic immunotherapeutic virus. Pembrolizumab (pembro) is a human programmed death receptor-1 (PD-1) blocking mAb. Active CVA21 replication mediates a cellular RIG-I response increasing levels of immune-checkpoint (CPK) molecules namely PD-L1 and immune-cell infiltration in the tumor microenvironment of treated human melanoma and bladder cancer lesions. IV delivery of CVA21 results in tumor targeting evidenced by detection of CVA21 viral RNA in tumor biopsies at study Day 8. The combination of IV CVA21+pembro may provide combinatorial benefit in the clinic.

Methods

KEYNOTE-200 is an on-going Phase Ib study with primary objectives to assess the safety and preliminary efficacy of IV CVA21 + pembro. Secondary objectives are to assess ORR by irRECIST, PFS, and OS. In the expansion cohort, 78 pts were given IV CVA21 + pembro, with IV CVA21 dose 1x109 TCID50 on study days 1, 3, 5, 8, 29 and Q3W for 6 additional infusions. Pembro was given at 200 mg IV Q3W from Day 8 for up to 2 years.

Results

The combination of IV CVA21 and pembro was generally well tolerated with no DLT’s and 12.8% (10/78 pts) G3 TRAE’s. No G4/5 TRAE’s have been observed. The ORR in evaluable CKP naïve NSCLC pts is currently 23% (7/31, 2CR+5PR) and 33% (7/21) in pts not harbouring EGFR or ALK mutations. In CPK naïve bladder cancer pts, most of whom were second line, the ORR is 31% (8/26, 3CR+5PR). Of note, was an ORR of 30% (3/10) in CPK naïve bladder cancer pts with neg PD-L1 tumor staining at baseline. Preliminary IHC staining of paired biopsies from evaluable CPK naïve pts with neg/low baseline PD-L1 revealed a notable increase in PD-L1+ tumor cells at Day 15 of 62% (8/13) of pts following treatment with CVA21 and pembro. The current median OS for CPK naïve NSCLC and bladder cancer pts is 9.5 and 11.2 mos, respectively. Prolonged SD was the best ORR observed in pts previously treated with CKP (n=17).

Conclusions

Systemic CVA21 with pembro has been well tolerated and has mediated encouraging clinical signals of activity in parallel with notable increases in PD-L1 tumor levels within these pt populations.

Clinical trial identification

NCT02043665

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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

901P - Impact of Prognostic Factors and Risk Groups on Overall Survival (OS) in Patients Treated With Pembrolizumab vs Investigator’s Choice Chemotherapy for advanced Urothelial Cancer (UC): Post Hoc Analysis of KEYNOTE-045

Presentation Number
901P
Lecture Time
13:05 - 13:05
Speakers
  • Joaquim Bellmunt (Boston, US)
Location
Hall A3 - Poster Area Networking Hub, ICM München, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

Well-defined prognostic factors (PF) and risk groups have been shown to impact OS in first- and second-line chemotherapy (chemo) for UC. Post hoc analysis of survival outcome per level of risk was conducted using data from the phase 3 KEYNOTE-045 trial (NCT02256436).

Methods

Data from the Oct 26, 2017 data cut were included. The presence or absence of 4 predefined criteria applied at study randomization was noted for each patient: ECOG PS (0 vs 1 or 2), hemoglobin level (<10 g/dL vs ≥ 10 g/dL), liver metastases (yes vs no), and time from prior chemotherapy (<3 months vs ≥ 3 months). Patients were grouped per the number of PFs they had (0, 1, 2, or 3/4), and OS was estimated for each risk group receiving pembrolizumab (pembro) or chemo, using Kaplan-Meier (K-M) statistics.

Results

Data from 529/542 patients were included. Stratified randomization ensured that the distribution of risk levels was similar between the 2 treatment arms. Overall, OS decreased with increasing numbers of PFs for pembro (from 19 to 5 months) and chemo (from 18 to 3 months) (Table). Within the chemo arm, the results of the K-M survival profiles were consistent with previously published data, in which each risk group had different outcomes. Within the pembro arm, outcomes of pts with 0 and 1 PF were distinct from those with 2 and 3/4 PF groups. OS was longer with pembro than with chemo across all PF subgroups.

0 PFS
1 PF
2 PFs
3 or 4 PFs
OSPembro n = 54Chemo n = 45Pembro n = 97Chemo n = 97Pembro n = 66Chemo n = 80Pembro n = 45Chemo n = 45
Median (95% CI),months18.5 (14.1-NE)17.6 (10.2-24.2)12.6 (8.1-18.9)8.8 (7.4-11.2)5.1 (2.8-8.7)4.7 (3.5-6.1)4.6 (2.3-7.4)3.4 (2.4-4.6)
24-month OS, %41.436.735.317.812.65.613.7NR
30-month OS, %41.431.625.913.7NR5.611.4NR
HR for OS0.81 (0.49-1.36)0.67 (0.48-0.93)0.82 (0.57-1.16)0.61 (0.39-0.97)

Conclusions

OS within the pembro and chemo arms decreased with increasing numbers of PFs. OS of patients treated with pembro was longer than those receiving chemo across the risk groups. Patients treated with pembro who had 2 or 3/4 PFs had overall similar outcomes. Additional analyses are needed to characterize novel risk models for patients treated with immunotherapies.

Clinical trial identification

NCT02256436, trial initiation date: October 3, 2014.

Legal entity responsible for the study

Merck & Co., Inc.

Funding

Merck & Co., Inc.

Editorial Acknowledgement

Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

J. Bellmunt: Consultant/advisory: Pierre Fabre, Astellas, Pfizer, Merck, Genentech, Novartis, AstraZeneca, BMS; Travel: Pfizer, MSD Oncology; Research funding: Millennium, Sanofi. R. de Wit: Consultant/advisory: Sanofi, Merck, Lilly, Roche/Genentech; Honoraria: Sanofi, Lilly, Roche/Genentech, Merck; Research funding: Sanofi. D.J. Vaughn: Research funding: Merck, Roche, Genentech. Y. Fradet: Consultant/Advisory: Merck, Astellas, Roche, AstraZeneca; Research funding: Astellas; Travel: Roche. J.L. Lee: Consultant/Advisory: Astellas, AstraZeneca, Eisai; Honoraria: Pfizer, Astellas, Novartis, BMS; Research funding: Pfizer, Janssen, Novartis, Exelixis, BMS, Roche/Genentech. L. Fong: Consultant/Advisory: Atreca, Ideava Biosciences, MIODx; Research funding: BMS, Abbvie, Roche/Genentech, Janssen, Merck, Nektar. N.J. Vogelzang: Consultant/Advisory: Amgen, Pfizer, Bayer, Genentech/Roche, AstraZeneca, Caris Life Science, Tolero; Speakers’ bureau: Bayer, Sanofi, BMS, Exelixis, AstraZeneca, Stock, Caris Life Sciences, Honoraria: Pfizer; Research funding: Endocyte, Merck. M.A. Climent: Honoraria: Roche, BMC, Bayer, Astella, Sanofi, Pfizer, Novartis; Consulting/Advisory: Janssen, Pfizer, Roche, Sanofi, Astellas Pharma, Bayer; Travel: Astellas, Janssen, Pfizer. D. Petrylak: Consultant/Advisory: Bayer, Johnson & Johnson, Exelixis, Ferring, Millennium, Medivation, Pfizer, Roche, Sanofi; Research funding: Johnson & Johnson, Sanofi, Endocyte, Genentech, Merck, Astellas, Novartis, AstraZeneca, Bayer, Lilly, Seattle Genetics. T.K. Choueiri: Consultant: Pfizer, Bayer, Novartis, GlaxoSmithKline, Merck, BMS Roche/Genentech, Eisai, AstraZeneca, Exelixis, Alligent; Honoraria: NCCN; Research funding: Pfizer, Novartis, Merck, Exelixis, GlaxoSmithKline, BMS, AstraZeneca, Roche/Genentech, Celldex. W.R. Gerritsen: Consultant/Advisory: BMS, Amgen, Merck, Aglaia Biomedical Ventures, Astellas, Bayer, Janssen-Cilag; Speakers’ bureau: Astellas, Bayer, Janssen-Cilag; Travel: Amgen, Bayer. H. Gurney: Consultant/Advisory: BMS, Ipsen, Merck, AstaZeneca; Travel: Astellas, Sanofi; Honoraria: Roche, Astellas; Research funding: Pfizer. D.I. Quinn: Consultant/Advisory: Astellas, Pfizer, BMS, Genetech/Roche, Merck, Bayer, Exelixis, AstraZeneca, Sanofi; Honoraria: Bayer, Astellas, Pfizer, Genentech/Roche, Merck, BMS, AstraZeneca, Sanofi, Millennium, Genentech/Roche, GlaxoSmithKline. S. Culine: Consultant/Advisory: Roche, Janssen; Speakers bureau: Astellas, Roche, Merck; Travel: Amgen, Astellas, Janssen. C.N. Sternberg: Honararia: OncoGenex, Lilly, Janssen, Merck, BMS, AstraZeneca, Roche/Genentech; Research funding: Lilly, Janssen, Merck, BMS, AstraZeneca, Roche/Genentech. E. Jensen: Employment: Merck. T. Frenkl, R.F. Perini: Employment and stock. D. Bajorin: BMS, Novartis, Roche/Genentech, Merck, Lilly, Fidia Farmaceutici, Urogen Pharma, Lilly Pfizer, EMD Serono; Honoraria: Merck; Research funding: Dendreon, Novartis, Amgen. Genentech/Roche, Merck, BMS. All other authors have declared no conflicts of interest.

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Poster Discussion session - Head and neck cancers Poster Discussion session

1047PD - Pembrolizumab for Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC): Post Hoc Analyses of Treatment Options From the Phase 3 KEYNOTE-040 Trial

Presentation Number
1047PD
Lecture Time
15:00 - 15:00
Speakers
  • Christophe Le Tourneau (Paris, FR)
Location
Hall B3 - Room 23, ICM München, Munich, Germany
Date
20.10.2018
Time
15:00 - 16:15

Abstract

Background

In the phase 3, randomized, open-label KEYNOTE-040 study (NCT02252042), pembrolizumab (pembro), compared with standard of care (SOC), prolonged survival in patients (pts) with recurrent and/or metastatic HNSCC that progressed during or after platinum-based therapy. Post hoc analyses were conducted to evaluate pembro vs SOC by (1) each of 3 SOC choices, (2) prior cetuximab, and (3) second PFS (PFS2; time from randomization to disease progression after initiation of new anticancer therapy).

Methods

Eligible pts (N = 495) randomly assigned (1:1) to receive pembro (200 mg every 3 weeks) or investigator choice of methotrexate (40 mg/m2 weekly), docetaxel (75 mg/m2 every 3 weeks), or cetuximab (400 mg/m2 loading dose then 250 mg/m2 weekly). Primary end point: OS; PFS and ORR were secondary end points.

Results

Outcomes for pembro vs each SOC choice are in the table. Regardless of prior cetuximab exposure, survival benefit with pembro was observed. There was a trend toward improved PFS and ORR in those with no prior cetuximab. In pts (N = 210) with no prior cetuximab, median OS was 8.2 vs 6.9 months (mo) for pembro vs SOC (HR 0.78; 95% CI 0.56-1.07; P = 0.062), median PFS was 2.9 vs 2.3 mo (HR 0.84; 95% CI 0.62-1.15; P = 0.135), and ORR was 21.6% vs 13.0% (P = 0.076). In pts (N = 285) who had prior cetuximab, median OS was 8.4 vs 7.1 mo for pembro vs SOC (HR 0.89; 95% CI 0.68-1.16; P = 0.191), median PFS was 2.1 vs 2.3 mo (HR 1.13; 95% CI 0.88-1.46; P = 0.825), and ORR was 9.7% vs 7.9% (P = 0.354). Median PFS2 was 6.6 vs 5.4 mo for pembro vs SOC (HR 0.75; 95% CI 0.62-0.91; P = 0.002).

Pembro n = 247Methotrexate n = 65Cetuximab n = 73Docetaxel n = 110
OS
Median, mo8.46.07.17.7
HR, pembro vs SOC (95% CI)0.81 (0.59-1.11)0.77 (0.57-1.03)0.81 (0.62-1.05)
P value0.0940.0380.058
PFS
Median, mo2.12.22.12.5
HR for pembro vs SOC (95% CI)0.95 (0.71-1.27)0.93 (0.70-1.23)1.02 (0.79-1.32)
P value0.3520.2990.557
Rate at 6 months, %25.621.521.917.9
ORR
ORR, %14.66.211.011.8
Difference for pembro vs SOC (95% CI)8.7 (–1.4 to 15.8)4.5 (–5.4 to 12.0)3.4 (–5.0 to 10.5)
P value0.0400.1630.202

Conclusions

The trend was toward improved OS for pembro vs all 3 SOC choices, regardless of prior cetuximab exposure. PFS and ORR were improved in those who had no prior cetuximab, although this may represent a less heavily pretreated population. Pembro, compared with SOC, improved PFS2. Future analyses will evaluate subsequent therapies after initial progression.

Clinical trial identification

NCT02252042; Trial initiated: September 29, 2014.

Legal entity responsible for the study

Merck & Co, Inc.

Funding

Merck & Co, Inc.

Editorial Acknowledgement

Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck & Co, Inc, Kenilworth, NJ, USA.

Disclosure

C. Le Tourneau: Honorararia: Bristol-Myers Squibb, MSD, Merck Serono, Nanobiotix, Amgen, Roche, Novartis; Travel expenses: Bristol-Myers Squibb, MSD, Merck Serono. E.E.W. Cohen: Consultant: Merck, BMS, AstraZeneca, Human Longevity, Inc, Pfizer, EMD Serono. K.J. Harrington: Honoraria, consultant, and speakers bureau: Amgen, AstraZeneca, Merck, Merck Sharp & Dohme, Pfizer, BMS; Research funding: AstraZeneca, Merck; Travel: Merck Sharp & Dohme. L. Licitra: Consultant: Eisai, Amgen, Boehringer Ingelheim, Debiopharm Group, AstraZeneca, Novartis, Bayer, Merck, Merck Serono, Roche, Bristol-Myers Squibb; Research funding: Eisai, Amgen, Merck Serono, Boehringer Ingelheim, AstraZenca, Novartis, Roche, Merck. M-J. Ahn: Advisory board member: AstraZeneca, Lilly, Lyzz, A. Soria: Personal fees for giving lectures: Bristol-Myers Squibb, Novartis, Roche, all outside the submitted work. J-P. Machiels: Advisory board member: MSD (uncompensated), Debio, Nanobiotix, Innate. R. Mehra: Previous employment spouse: GlaxoSmithKline; Advisory board member: Bayer, Bristol-Myers Squibb, Genentech, InnatePharma, all outside the submitted work. B. Burtness: Advisory board member: Merck, Astra-Zeneca, Bristol-Myers Squibb, Aduro, Amgen, Genentech; Research funding: Merck, Advaxis, Bristol-Myers Squibb; Honoraria: IDDI; Travel, accommodation, expenses: Boehringer Ingelheim. P. Zhang: Employment and travel: Merck. J. Cheng, R. Swaby: Employment and stock: Merck. D. Soulières: Advisory board member and research funding: Merck. All other authors have declared no conflicts of interest.

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Presidential Symposium 3 Proffered Paper session

LBA8_PR - KEYNOTE-048: Phase 3 study of first-line pembrolizumab (P) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC)

Presentation Number
LBA8_PR
Lecture Time
16:30 - 16:45
Speakers
  • Barbara Burtness (New Haven, US)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
22.10.2018
Time
16:30 - 18:00

Abstract

Background

KEYNOTE-048 was an open-label, randomized phase 3 study of P or P + chemotherapy (C) vs EXTREME (E) as first-line systemic therapy for R/M HNSCC (NCT02358031).

Methods

Patients (pts) with R/M HNSCC not curable by local therapy and with no prior systemic therapy (R/M setting) who provided a tumor sample for PD-L1 testing were randomized to P 200 mg Q3W, P + C (cisplatin 100 mg/m2 or carboplatin AUC 5 Q3W + 5-FU 1000 mg/m2/d for 4 d Q3W), or E (cetuximab 400 mg/m2 loading/250 mg/m2 QW + C) given until PD, unacceptable toxicity, 6 cycles (C), or 24 mo (P). Primary end points for P vs E and P + C vs E were PFS and OS in the PD-L1 combined positive score (CPS) ≥20 and ≥1 and total populations (pop). Cutoff date for this final PFS/interim OS analysis was Jun 13, 2018 (minimum follow-up, ~17 mo).

Results

882 pts were randomized: 301 to P, 281 to P + C, 300 to E. P was superior to E for OS in CPS ≥20 (N = 255; median 14.9 vs 10.7 mo; HR 0.61 [95% CI 0.45-0.83]; P = 0.0007) and ≥1 (N = 512; median 12.3 vs 10.3 mo; HR 0.78 [95% CI 0.64-0.96]; P = 0.0086); OS for P was non-inferior to E in the total pop (N = 601). P did not prolong PFS in CPS ≥20 (P = 0.5); per the analysis plan, no further PFS testing was done for P vs E. Confirmed ORR (P vs E) was 23% vs 36% for CPS ≥20, 19% vs 35% for CPS ≥1, and 17% vs 36% for the total pop; median DOR was 20.9 vs 4.2 mo, 20.9 vs 4.5 mo, and 20.9 vs 4.5 mo. Gr 3-5 drug-related AE rates were 17% (P) vs 69% (E). P + C was non-inferior and superior to E for OS in the total pop (N = 559; median 13.0 vs 10.7 mo; HR 0.77 [95% CI 0.63-0.93]; P = 0.0034); OS for P + C was not significantly superior to E in CPS ≥20 and ≥1 at this interim analysis. PFS was not prolonged with P + C (P = 0.2). For P + C vs E, confirmed ORR was 36% vs 36%, median DOR was 6.7 vs 4.3 mo, and gr 3-5 drug-related AE rates were 71% vs 69%.

Conclusions

For first-line R/M HNSCC, P significantly improved OS over E in the PD-L1 CPS ≥20 and ≥1 populations and was noninferior in the total population with favorable safety. P + C significantly improved OS in the total population with safety comparable to E. P and P + C responses were durable. These data support pembrolizumab and pembrolizumab + platinum + 5-FU as new first-line standards of care for R/M HNSCC. The study continues to the final OS analysis.

Clinical trial identification

NCT02358031: Trial initiation, February 6, 2015

Editorial Acknowledgement

Medical writing and editorial assistance was provided by Melanie Leiby, an employee of Merck & Co., Inc., Kenilworth, NJ, USA.

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Poster Discussion session - NSCLC, metastatic 2 Poster Discussion session

LBA63 - Long-term survival in patients (pts) with advanced NSCLC in the KEYNOTE-010 study overall and in pts who completed 2 years of pembrolizumab (pembro)

Presentation Number
LBA63
Lecture Time
16:45 - 16:45
Speakers
  • Roy S. Herbst (New Haven, US)
Location
ICM - Room 13, ICM München, Munich, Germany
Date
21.10.2018
Time
16:45 - 17:45

Abstract

Background

KEYNOTE-010 (NCT01905657) is a global, open-label, phase 2/3 study of pembro 10 mg/kg or 2 mg/kg Q3W vs docetaxel in pts with previously treated advanced NSCLC with PD-L1 TPS ≥1%. Pembro improved OS vs docetaxel in the PD-L1 TPS ≥1% and ≥50% co-primary analyses (median follow-up, 13.1 mo), with no difference between pembro doses. We present updated OS for the study overall and results for pts who completed 35 cycles (~2 y) of pembro.

Methods

Pts >18 years with previously treated advanced NSCLC with PD-L1 TPS ≥1% were randomized (1:1:1) to pembro 10 mg/kg or 2 mg/kg Q3W, or docetaxel 75 mg/m2 Q3W. Pts received pembro for 35 cycles or until disease progression/intolerable toxicity. After the primary analysis, crossover from docetaxel to pembro was allowed. Response was assessed every 9 wk (RECIST 1.1 by independent central review), and survival every 2 mo after treatment ended. OS was a primary endpoint. Pembro doses were pooled.

Results

As of March 16, 2018, median (range) follow-up was 42.5 (35.2–53.2) mo. Among all pts (N=1033), pembro improved OS vs docetaxel (HR, 0.69; 95% CI, 0.60–0.80; P<0.00001), with median (95% CI) OS of 11.8 (10.4–13.1) mo vs 8.4 (7.6–9.5) mo, and 36-mo OS rate of 23% vs 11%, respectively. Incidence of grade 3–5 treatment-related AEs was similar to the primary analysis: 16% of pts in the pembro group and 36% in the docetaxel group had grade 3–5 treatment-related AEs (0.7% and 1.6%, respectively, had grade 5 AEs). 22% and 9% of pts, respectively, had immune-mediated AEs and infusion reactions. Among 79 pts who completed 35 pembro cycles, the 36-mo OS rate was 99% and 95% had PR/CR as best response. Response was ongoing in 44 pts (59%); median duration of response was not reached (range, 1+ to 46+ mo). 25 of 79 pts (32%) had PD (investigator review) after stopping 35 cycles of treatment, 13 of whom started second course pembro.

Conclusions

With an additional 30-mo follow-up from the primary analyses, pembro continued to prolong OS vs docetaxel in pts with previously treated, PD-L1–expressing advanced NSCLC, with manageable long-term safety. Most pts who completed 2 y of pembro had durable response, and the majority of pts who had PD after stopping 35 cycles of pembro were able to receive a second course of pembro.

Clinical trial identification

ClinicalTrials.gov, NCT01905657

Editorial Acknowledgement

Medical writing and editorial assistance was provided by C4 MedSolutions, LLC (Yardley, PA), a CHC Group company. This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

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