PMID- 36940261
OWN - NLM
STAT- MEDLINE
DCOM- 20230608
LR  - 20240312
IS  - 1549-490X (Electronic)
IS  - 1083-7159 (Print)
IS  - 1083-7159 (Linking)
VI  - 28
IP  - 6
DP  - 2023 Jun 2
TI  - Atezolizumab Plus PEGPH20 Versus Chemotherapy in Advanced Pancreatic Ductal 
      Adenocarcinoma and Gastric Cancer: MORPHEUS Phase Ib/II Umbrella Randomized Study 
      Platform.
PG  - 553-e472
LID - 10.1093/oncolo/oyad022 [doi]
AB  - BACKGROUND: The MORPHEUS platform comprises multiple open-label, randomized, 
      phase Ib/II trials designed to identify early efficacy and safety signals of 
      treatment combinations across cancers. Atezolizumab (anti-programmed cell death 1 
      ligand 1 [PD-L1]) was evaluated in combination with PEGylated recombinant human 
      hyaluronidase (PEGPH20). METHODS: In 2 randomized MORPHEUS trials, eligible 
      patients with advanced, previously treated pancreatic ductal adenocarcinoma 
      (PDAC) or gastric cancer (GC) received atezolizumab plus PEGPH20, or control 
      treatment (mFOLFOX6 or gemcitabine plus nab-paclitaxel [MORPHEUS-PDAC]; 
      ramucirumab plus paclitaxel [MORPHEUS-GC]). Primary endpoints were objective 
      response rates (ORR) per RECIST 1.1 and safety. RESULTS: In MORPHEUS-PDAC, ORRs 
      with atezolizumab plus PEGPH20 (n = 66) were 6.1% (95% CI, 1.68%-14.80%) vs. 2.4% 
      (95% CI, 0.06%-12.57%) with chemotherapy (n = 42). In the respective arms, 65.2% 
      and 61.9% had grade 3/4 adverse events (AEs); 4.5% and 2.4% had grade 5 AEs. In 
      MORPHEUS-GC, confirmed ORRs with atezolizumab plus PEGPH20 (n = 13) were 0% (95% 
      CI, 0%-24.7%) vs. 16.7% (95% CI, 2.1%-48.4%) with control (n = 12). Grade 3/4 AEs 
      occurred in 30.8% and 75.0% of patients, respectively; no grade 5 AEs occurred. 
      CONCLUSION: Atezolizumab plus PEGPH20 showed limited clinical activity in 
      patients with PDAC and none in patients with GC. The safety of atezolizumab plus 
      PEGPH20 was consistent with each agent's known safety profile. 
      (ClinicalTrials.gov Identifier: NCT03193190 and NCT03281369).
CI  - (c) The Author(s) 2023. Published by Oxford University Press.
FAU - Ko, Andrew H
AU  - Ko AH
AD  - Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, 
      University of California San Francisco, San Francisco, CA, USA.
FAU - Kim, Kyu-Pyo
AU  - Kim KP
AD  - Department of Oncology, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul, Republic of Korea.
FAU - Siveke, Jens T
AU  - Siveke JT
AD  - Department of Medical Oncology and Division of Solid Tumor Translational 
      Oncology, German Cancer Consortium (DKTK/DKFZ, partner site Essen), West German 
      Cancer Center, University Hospital Essen, Essen, Germany.
FAU - Lopez, Charles D
AU  - Lopez CD
AD  - Division of Hematology Oncology, Oregon Health & Science University, Knight 
      Cancer Institute, Portland, OR, USA.
FAU - Lacy, Jill
AU  - Lacy J
AD  - Department of Medicine, Section of Medical Oncology, Yale School of Medicine, 
      Yale University, New Haven, CT, USA.
FAU - O'Reilly, Eileen M
AU  - O'Reilly EM
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 
      USA.
FAU - Macarulla, Teresa
AU  - Macarulla T
AD  - Gastrointestinal Cancer Unit, Vall d'Hebron University Hospital and Vall d'Hebron 
      Institute of Oncology (VHIO), Barcelona, Spain.
FAU - Manji, Gulam A
AU  - Manji GA
AD  - Division of Hematology and Oncology, Columbia University Irving Medical Center, 
      New York, NY, USA.
FAU - Lee, Jeeyun
AU  - Lee J
AD  - Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University 
      School of Medicine, Seoul, Republic of Korea.
FAU - Ajani, Jaffer
AU  - Ajani J
AD  - Department of Gastrointestinal Medical Oncology, The University of Texas MD 
      Anderson Cancer Center, Houston, TX, USA.
FAU - Alsina Maqueda, Maria
AU  - Alsina Maqueda M
AD  - Gastrointestinal Cancer Unit, Vall d'Hebron University Hospital and Vall d'Hebron 
      Institute of Oncology (VHIO), Barcelona, Spain.
FAU - Rha, Sun-Young
AU  - Rha SY
AD  - Department of Internal Medicine, Yonsei Cancer Center, Yonsei University Health 
      System, Seoul, Republic of Korea.
FAU - Lau, Janet
AU  - Lau J
AD  - Genentech, Inc., South San Francisco, CA, USA.
FAU - Al-Sakaff, Nedal
AU  - Al-Sakaff N
AD  - F. Hoffmann-La Roche, Ltd, Basel, Switzerland.
FAU - Allen, Simon
AU  - Allen S
AD  - Genentech, Inc., South San Francisco, CA, USA.
FAU - Lu, Danny
AU  - Lu D
AD  - Hoffmann-La Roche Limited, Mississauga, ON, Canada.
FAU - Shemesh, Colby S
AU  - Shemesh CS
AD  - Genentech, Inc., South San Francisco, CA, USA.
FAU - Gan, Xinxin
AU  - Gan X
AD  - Product Development Safety, Roche (China) Holding Ltd, Shanghai, People's 
      Republic of China.
FAU - Cha, Edward
AU  - Cha E
AD  - Genentech, Inc., South San Francisco, CA, USA.
FAU - Oh, Do-Youn
AU  - Oh DY
AD  - Department of Internal Medicine, Cancer Research Institute, Seoul National 
      University College of Medicine, Seoul, Republic of Korea.
AD  - Department of Internal Medicine, Seoul National University Hospital, Seoul, 
      Republic of Korea.
AD  - Integrated Major in Innovative Medical Science, Seoul National University 
      Graduate School, Seoul, Republic of Korea.
LA  - eng
SI  - ClinicalTrials.gov/NCT03281369
SI  - ClinicalTrials.gov/NCT03193190
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncologist
JT  - The oncologist
JID - 9607837
RN  - 52CMI0WC3Y (atezolizumab)
RN  - EC 3.2.1.35 (Hyaluronoglucosaminidase)
RN  - P88XT4IS4D (Paclitaxel)
RN  - EC 3.2.1.35 (PEGPH20)
SB  - IM
MH  - Humans
MH  - *Adenocarcinoma/drug therapy
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - *Carcinoma, Pancreatic Ductal/drug therapy
MH  - Hyaluronoglucosaminidase/adverse effects
MH  - Paclitaxel/adverse effects
MH  - *Pancreatic Neoplasms/drug therapy/pathology
MH  - *Stomach Neoplasms/drug therapy
PMC - PMC10243783
OTO - NOTNLM
OT  - PD-L1
OT  - basket study
OT  - combination therapy
OT  - gastric cancer
OT  - hyaluronan
OT  - immunotherapy
OT  - pancreatic cancer
OT  - proof of concept
COIS- All authors received support from F. Hoffmann-La Roche/Genentech during the 
      conduct of this study. Andrew H. Ko: Roche/Genentech (consulting/advisory 
      relationship and research funding). Jens T. Siveke: AstraZeneca, Bayer, 
      Immunocore, Roche/Genentech, Servier (honoraria), Bristol Myers Squibb, Celgene, 
      Roche/Genentech, Pharma15 (Board of Directors, consulting/advisory relationship), 
      Bristol Myers Squibb, Celgene, Roche/Genentech (research funding), and Pharma15 
      (intellectual property rights/inventor/patent holder). Charles D. Lopez: Servier 
      Pharmaceuticals, Taiho Pharmaceuticals, Genentech/Roche (research funding). Jill 
      Lacy: Ipsen, Novartis, Deciphera, Merck, Equinox, Techspert, Guidepoint, 
      KeyQuest, FirstWorld Group, Aptitude Health, Brass Tacks Health 
      (consulting/advisory relationship). Eileen M. O'Reilly: CytomX Therapeutics and 
      Rafael Therapeutics (DSMB), Seagen, Boehringer Ingelheim, BioNTech, Ipsen, Merck, 
      IDEAYA, Silenseed, Novartis, AstraZeneca, Noxxon, BioSapien, Cend Therapeutics, 
      Thetis, Autem, ZielBio, Tempus (consulting/advisory relationship), Agios, 
      Genentech-Roche, Eisai, Zymeworks (spouse: consulting/advisory relationship), 
      Genentech/Roche, Celgene/BMS, BioNTech, AstraZeneca, Arcus, Elicio, Parker 
      Institute (research funding). Teresa Macarulla: Ability Pharmaceuticals SL, 
      Amgen, Aptitude Health, AstraZeneca, Basilea Pharma, Baxter, BioLineRX Ltd., 
      Celgene, Eisai, Ellipses, Genzyme, Hirslanden/GITZ, Imedex, Incyte, Ipsen 
      Bioscience, Inc., Janssen, Lilly, Marketing Farmaceutico & Investigacion Clinica, 
      S.L., MDS, Medscape, Novocure, Paraxel, PPD Development, Polaris, QED 
      Therapeutics, Roche Farma, Sanofi-Aventis, Servier, Scilink Comunicacion 
      Cientifica SC, Surface Oncology, Zymeworks (consulting/advisory relationship), 
      Abbvie Farmaceutica, Ability Pharmaceuticals, Agios Pharmaceuticals, AMC Medical 
      Research, Amgen, Armo Biosciences, Aslan Pharmaceuticals, AstraZeneca, Basilea 
      Pharmaceutica International, Bayer, BeiGene, BioKeralty Research Institute, 
      BioLineRx, Blueprint Medicines, Boston Biomedical, Bristol Myers Squibb (BMS), 
      Cantargia, Celgene, Eisai, Erytech Pharma, European Organisation for Research and 
      Treatment of Cancer (EORTC), F. Hoffmann-La Roche, FibroGen, Halozyme, Incyte, 
      Ipsen Bioscience, Ipsen Pharma, Lilly, Loxo Oncology, Medimmune, Merck Sharp & 
      Dohme, Nelum, Novartis, Novocure, OncoMed Pharmaceuticals, QED Therapeutics, VCN 
      Biosciences, Zymeworks (research funding), Servier, prIME, AstraZeneca, Sanofi, 
      and Incyte (H). Gulam A. Manji: Roche/Genentech, CEND Pharmaceutical 
      (consulting/advisory relationship), Roche/Genentech, Regeneron, BiolonRX, Merck 
      (research funding), Amgen, Lilly, Roche (honoraria), CEND Pharmaceuticals 
      (intellectual property rights/inventor/patent holder). Jeeyun Lee: OncXerna, 
      Mirati, Guardant (consulting/advisory relationship), AstraZeneca, Merck MSD 
      (research funding). Jaffer Ajani: BMS, Merck, Astellas, Amgen, Novartis, 
      Zymeworks (honoraria), BMS, Roche, Merck, Prolinx, DF, Zymeworks, Astellas, 
      Taiho, Leap, Gilead, LaNova (research funding). Maria Alsina Maqueda: Amgen, BMS, 
      Lilly, MSD, Roche, Servier (honoraria), BMS, Lilly, MSD, Servier 
      (consulting/advisory relationship). Sun-Young Rha: MSD, BMS/Ono, Daiichi Sankyo, 
      Amgen, Indivumed, LG Biochemical (consulting/advisory relationship), Lilly, 
      Merck, BMS, MSD (expert testimony), Amgen, BMS/Ono, Daiichi Sankyo, AstraZeneca, 
      Roche, Merck, Lilly, MSD, BeiGene, Zymeworks (research funding). Janet Lau, Simon 
      Allen, Danny Lu, Colby S. Shemesh, Xinxin Gan, Edward Cha, and Nedal Al-Sakaff: 
      F. Hoffmann-La Roche Ltd./Genentech Inc. (employment and intellectual property 
      rights/inventor/patent holder). Do-Youn Oh: AstraZeneca, Novartis, 
      Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, 
      BMS/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences, IQVIA 
      (consulting/advisory relationship), AstraZeneca, Novartis, Array, Eli Lilly, 
      Servier, BeiGene, MSD, Handok (research funding).
EDAT- 2023/03/21 06:00
MHDA- 2023/06/08 06:42
PMCR- 2023/03/20
CRDT- 2023/03/20 14:12
PHST- 2022/11/30 00:00 [received]
PHST- 2023/01/18 00:00 [accepted]
PHST- 2023/06/08 06:42 [medline]
PHST- 2023/03/21 06:00 [pubmed]
PHST- 2023/03/20 14:12 [entrez]
PHST- 2023/03/20 00:00 [pmc-release]
AID - 7081215 [pii]
AID - oyad022 [pii]
AID - 10.1093/oncolo/oyad022 [doi]
PST - ppublish
SO  - Oncologist. 2023 Jun 2;28(6):553-e472. doi: 10.1093/oncolo/oyad022.