PMID- 30570763
OWN - NLM
STAT- MEDLINE
DCOM- 20200813
LR  - 20200813
IS  - 1552-4604 (Electronic)
IS  - 0091-2700 (Print)
IS  - 0091-2700 (Linking)
VI  - 59
IP  - 5
DP  - 2019 May
TI  - Development of a Subcutaneous Fixed-Dose Combination of Pertuzumab and 
      Trastuzumab: Results From the Phase Ib Dose-Finding Study.
PG  - 702-716
LID - 10.1002/jcph.1362 [doi]
AB  - Adding pertuzumab to trastuzumab (both monoclonal antibodies targeting human 
      epidermal growth factor receptor 2 [HER2]) has proven survival benefits when 
      combined with chemotherapy for patients with HER2-positive breast cancer. The 
      combination of pertuzumab and trastuzumab together in 1 vial for subcutaneous 
      (SC) administration is being developed as a ready-to-use formulation to reduce 
      the treatment burden on patients while improving healthcare efficiency. An 
      open-label, 2-part, phase Ib dose-finding study (NCT02738970) was undertaken in 
      healthy male volunteers (part 1) and female patients with HER2-postive early 
      breast cancer who had completed standard (neo)adjuvant treatment (part 2). This 
      study aimed to identify an SC pertuzumab dose given with recombinant human 
      hyaluronidase that results in comparable exposure to that of the intravenous (IV) 
      pertuzumab dose, based on pertuzumab serum trough concentration and area under 
      the serum concentration-time curve. Pharmacokinetics (PK), safety, and 
      tolerability of a single dose of SC pertuzumab given alone or in a fixed-dose 
      combination (comixed or coformulated) with trastuzumab were also assessed. A 
      maintenance dose of 600 mg for SC pertuzumab resulted in an equivalent exposure 
      to that of IV pertuzumab, and no new safety signals were identified for SC 
      pertuzumab or trastuzumab. A loading dose of 1200 mg for SC pertuzumab was 
      selected based on approximate dose proportionality. The PK and safety results 
      support further development of a fixed-dose coformulation combination of 
      pertuzumab and trastuzumab for SC administration, which will be investigated in 
      an upcoming phase III trial in patients with HER2-positive early breast cancer.
CI  - (c) 2018, The American College of Clinical Pharmacology.
FAU - Kirschbrown, Whitney P
AU  - Kirschbrown WP
AD  - Genentech, Inc., South San Francisco, CA, USA.
FAU - Wynne, Chris
AU  - Wynne C
AD  - Christchurch Clinical Studies Trust, Christchurch, New Zealand.
FAU - Kagedal, Matts
AU  - Kagedal M
AD  - Genentech, Inc., South San Francisco, CA, USA.
FAU - Wada, Russ
AU  - Wada R
AD  - Certara, Menlo Park, CA, USA.
FAU - Li, Hanbin
AU  - Li H
AD  - Certara, Menlo Park, CA, USA.
FAU - Wang, Bei
AU  - Wang B
AD  - Genentech, Inc., South San Francisco, CA, USA.
FAU - Nijem, Ihsan
AU  - Nijem I
AD  - Genentech, Inc., South San Francisco, CA, USA.
FAU - Badovinac Crnjevic, Tanja
AU  - Badovinac Crnjevic T
AD  - F. Hoffmann-La Roche Limited, Basel, Switzerland.
FAU - Gasser, Helena
AU  - Gasser H
AD  - F. Hoffmann-La Roche Limited, Basel, Switzerland.
FAU - Heeson, Sarah
AU  - Heeson S
AD  - Roche Products Limited, Welwyn Garden City, UK.
FAU - Eng-Wong, Jennifer
AU  - Eng-Wong J
AD  - Genentech, Inc., South San Francisco, CA, USA.
FAU - Garg, Amit
AU  - Garg A
AD  - Genentech, Inc., South San Francisco, CA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02738970
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20181219
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - K16AIQ8CTM (pertuzumab)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Administration, Intravenous
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Antineoplastic Agents, Immunological/administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Breast Neoplasms/*drug therapy/metabolism
MH  - Drug Therapy, Combination/adverse effects/*methods
MH  - Female
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Male
MH  - Middle Aged
MH  - Receptor, ErbB-2/metabolism
MH  - Trastuzumab/*administration & dosage/adverse effects/pharmacokinetics
MH  - Treatment Outcome
PMC - PMC7027517
OTO - NOTNLM
OT  - HER2-positive
OT  - breast cancer
OT  - dose-finding
OT  - pertuzumab
OT  - population pharmacokinetics
OT  - subcutaneous
OT  - trastuzumab
EDAT- 2018/12/21 06:00
MHDA- 2020/08/14 06:00
PMCR- 2020/02/18
CRDT- 2018/12/21 06:00
PHST- 2018/10/02 00:00 [received]
PHST- 2018/11/26 00:00 [accepted]
PHST- 2018/12/21 06:00 [pubmed]
PHST- 2020/08/14 06:00 [medline]
PHST- 2018/12/21 06:00 [entrez]
PHST- 2020/02/18 00:00 [pmc-release]
AID - JCPH1362 [pii]
AID - 10.1002/jcph.1362 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2019 May;59(5):702-716. doi: 10.1002/jcph.1362. Epub 2018 Dec 
      19.