Abstract 76P
Background
Pembro has well characterized, manageable safety in the advanced setting. Clinical data suggest pembro has a similar profile in the adjuvant setting; further characterization is important given the extended life expectancy of pts with resectable disease.
Methods
Safety data from pts with resected stage IIIA-C (AJCC 7th ed) melanoma (KEYNOTE-054), resected stage IB-IIIA (AJCC 7th ed) NSCLC (PEARLS/KEYNOTE-091), RCC post-nephrectomy/metastasectomy (KEYNOTE-564), and resected stage IIB-C (AJCC 8th ed) melanoma (KEYNOTE-716) were pooled. Pts received adjuvant pembro 200 mg (2 mg/kg pediatric pts) Q3W or placebo for up to ∼1 yr. Safety was monitored for ≤30 days after treatment end (90 days for serious AEs). AEs were graded using NCI CTCAE v4.0.
Results
Data from 4125 pts were pooled (pembro, n=2060; placebo, n=2065). Median age was 61.0 yrs; 1351 (65.6%) pts treated with pembro and 1343 (65.0%) with placebo were male. Any-grade treatment-related AEs (TRAEs) occurred in 1620 (78.6%) pts treated with pembro and 1212 (58.7%) with placebo. Grade 3-5 TRAEs occurred in 336 (16.3%) pts treated with pembro and 72 (3.5%) with placebo; most common were diarrhea (n=23; 1.1%), ALT increased (n=20; 1.0%), and colitis (n=20; 1.0%) with pembro and lipase increased (n=13; 0.6%) and fatigue (n=6; 0.3%) with placebo. 4 pts in the pembro group died due to a TRAE. TRAEs led to discontinuation in 326 (15.8%) pts treated with pembro and 44 (2.1%) with placebo. Immune-mediated AEs (imAEs) and infusion reactions occurred in 761 (36.9%) pts treated with pembro and 193 (9.3%) with placebo (grade 3-5: n=181 [8.8%] vs n=23 [1.1%]). Most common imAEs were hypothyroidism (n=382; 18.5%), hyperthyroidism (n=227; 11.0%), and pneumonitis (n=82; 4.0%) with pembro and hypothyroidism (n=76; 3.7%), pneumonitis (n=29; 1.4%), and hyperthyroidism (n=27; 1.3%) with placebo. Median time to onset of first imAE or infusion reaction was 2.6 mo with pembro and 4.1 mo with placebo.
Conclusions
Data from this pooled analysis of >4000 patients across several tumor types show that adjuvant pembro has a manageable safety profile consistent in severity and management with the established profile of pembro in advanced disease.
Clinical trial identification
NCT02362594 (first posted to clinicaltrials.gov: Feb 13, 2015); NCT02504372 (first posted to clinicaltrials.gov: July 21, 2015); NCT03142334 (first posted to clinicaltrials.gov: May 5, 2017); NCT03553836 (first posted to clinicaltrials.gov: Jun 12, 2018).
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Jemimah Walker, PhD, and Holly C. Cappelli, PhD, CMPP, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Llc, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme Llc, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Funding
Funding for this research was provided by Merck Sharp & Dohme Llc, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Disclosure
J.J. Luke: Financial Interests, Personal, Other, DSMB: AbbVie, Immutep, Evaxion; Financial Interests, Personal, Advisory Board: 7 Hills, Bright Peak, Exo, Fstar, Inzen, RefleXion, Xilio, Actym, Alphamab Oncology, Arch Oncology, Duke Street Bio, Kanaph, Mavu, NeoTx, Onc.AI, OncoNano, Pyxis, Saros, STipe, Tempest; Financial Interests, Personal, Advisory Role: AbbVie, Alnylam, Atomwise, Bayer, Bristol-Myers Squibb, Castle, Checkmate, Codiak, Crown, Cugene, Curadev, Day One, Eisai, EMD Serono, Endeavor, Flame, G1 Therapeutics, Genentech, Gilead, Glenmark, HotSpot, Kadmon, KSQ, Janssen, Ikena, Inzen, Immatics, Immunocore, Incyte, Instil, IO Biotech, Macrogenics, Merck, Mersana, Nektar, Novartis, Partner, Pfizer, Pioneering Medicines, PsiOxus, Regeneron, Ribon, Roivant, Servier, STINGthera, Synlogic, Synthekine; Financial Interests, Institutional, Research Grant: AbbVie, Astellas, AstraZeneca, Bristol-Myers Squibb, Corvus, Day One, EMD Serono, Fstar, Genmab, Ikena, Immatics, Incyte, Kadmon, KAHR, Macrogenics, Merck, Moderna, Nektar, Next Cure, Numab, Palleon, Pfizer, Replimmune, Rubius, Servier, Synlogic, Takeda, Trishula, Tizona, Xencor. G.V. Long: Financial Interests, Personal, Other, Consultant/Advisor: Agenus, Amgen, Array Biopharma, Boehringer Ingelheim International GmbH , Bristol Myers Squibb , Evaxion Biotech A/S , Hexal AG (Sandoz Company) , Highlight Therapeutics S.l., Innovent Biologics USA Inc, Merck Sharp & Dohme (Australia) Pty Limited , Merck Sharp & Dohme, Novartis Pharma AG, OncoSec Medical Australia, PHMR Limited, Pierre Fabre , Provectus Australia , Qbiotics Group Limited , Regeneron Pharmaceuticals Inc. C. Robert: Financial Interests, Personal, Advisory Board: BMS, Roche, Pierre Fabre, Novartis, Sanofi, MSD, Pfizer, AstraZeneca. M.S. Carlino: Financial Interests, Personal, Advisory Board: Amgen, Bristol Myers Squibb, Eisai, Ideava, Merck Sharp & Dohme, Nektar, Novartis, Oncosec, Pierre-Fabre, Obiotics, Regeneron, Roche. T.K. Choueiri: Financial Interests, Personal and Institutional, Funding: AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers-Squibb, Calithera, Circle Pharma, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, IQVA, Infinity, Ipsen, Jansen, Kanaph, Lilly, Merck, Nikang, Nuscan, Novartis, Pfizer, Roche, Sanofi/Aventis, Surface Oncology; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers-Squibb, Calithera, Circle Pharma, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, IQVA, Infinity, Ipsen, Jansen, Kanaph, Lilly, Merck, Nikang, Nuscan, Novartis, Pfizer, Roche, Sanofi/Aventis, Surface Oncology; Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers-Squibb, Calithera, Circle Pharma, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, IQVA, Infinity, Ipsen, Jansen, Kanaph, Lilly, Merck, Nikang, Nuscan, Novartis, Pfizer, Roche, Sanofi/Aventis, Surface Oncology; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers-Squibb, Calithera, Circle Pharma, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, IQVA, Infinity, Ipsen, Jansen, Kanaph, Lilly, Merck, Nikang, Nuscan, Novartis, Pfizer, Roche, Sanofi/Aventis, Surface Oncology; Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers-Squibb, Calithera, Circle Pharma, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, IQVA, Infinity, Ipsen, Jansen, Kanaph, Lilly, Merck, Nikang, Nuscan, Novartis, Pfizer, Roche, Sanofi/Aventis, Surface Oncology; Non-Financial Interests, Personal and Institutional, Invited Speaker: Peerview, OncLive, MJH. N.B. Haas: Financial Interests, Personal, Advisory Board: Aveo, Eisai, Roche Genentech, Merck; Financial Interests, Personal, Invited Speaker: Exelixis. M.E.R. O'Brien: Financial Interests, Personal and Institutional, Advisory Board: Royal Marsden Hospital; Financial Interests, Personal and Institutional, Invited Speaker: Royal Marsden Hospital; Financial Interests, Personal and Institutional, Funding: Royal Marsden Hospital; Financial Interests, Personal and Institutional, Principal Investigator: Royal Marsden Hospital. S. Peters: Financial Interests, Institutional, Other, Consultant/Advisor: AbbVie, AiCME, Amgen, Arcus, AstraZeneca, Bayer, Beigene, Biocartis, BioInvent, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Provectus Australia, Eli Lilly, Elsevier; Financial Interests, Institutional, Other, Consultant, Advisory: F-Star, Fishawack, Foundation Medicine, Genzyme, Gilead, GSK, Illumina; Financial Interests, Institutional, Other, Consultant/Advisory: Imedex, IQVIA, Incyte, iTeos, Janssen, Medscape, Medtoday, Merck Sharp and Dohme, Merck Serono, Merrimack, Novartis, Novocure, OncologyEducation, Pharma Mar, Phosplatin Therapeutics, PER, Peerview, Pfizer, PRIME, Regeneron, RMEI, Roche/Genentech, RTP, Sanofi, Seattle Genetics, Takeda, Vaccibody; Financial Interests, Institutional, Invited Speaker: AiCME, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, ecancer, Eli Lilly, Foundation Medicine, Illumina, Imedex, Medscape, Merck Sharp and Dohme, Mirati, Novartis, PER, Peerview, Pfizer, Prime, Roche/Genentech, RTP, Sanofi, Takeda; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Beigene, Bristol-Myers Squibb, GSK, Merck Sharp and Dohme, Roche/Genentech. M.A. Leiby: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Llc; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. J. Lin: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. Y. Zhao: Financial Interests, Personal, Full or part-time Employment: Merck; Non-Financial Interests, Personal, Member: Merck. C. Krepler: Financial Interests, Personal, Stocks/Shares: Merck; Financial Interests, Personal, Full or part-time Employment: Merck. R.F. Perini: Financial Interests, Personal, Stocks/Shares: Merck; Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Llc. M.C. Pietanza: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Llc; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. A. Samkari: Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.; Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Llc. T. Gruber: Financial Interests, Personal, Full or part-time Employment: Merck, Clinical Safety and Risk Management; Financial Interests, Personal, Stocks/Shares: Merck, Clinical Safety and Risk Management; Financial Interests, Institutional, Leadership Role: Merck, Clinical Safety and Risk Management. N. Ibrahim: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Llc; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. A.M.M. Eggermont: Financial Interests, Personal, Speaker’s Bureau: BMS, Merck; Financial Interests, Personal, Advisory Board: Agenus, BioInvent, Brenus,CatalYm, Clover, Ellipses, Galecto, GenOway, GSK, IO Biotech, IQVIA, ISA Pharmaceuticals, Merck/MSD, Sairopa, Scorpion, Sellas, SkylineDX, TigaTX, Trained Therapeutics Discovery; Financial Interests, Personal, Stocks/Shares: IOBiotech, Sairopa, SkylineDX; Financial Interests, Personal, Principal Investigator: KEYNOTE-054; Financial Interests, Personal, Other, IDMC: BioNTech, IQVIA, GSK, Pfizer. All other authors have declared no conflicts of interest.