Evidence map›Paper›PMID 37420274›Full record

ArticleMolecular cancer therapeutics2023

Safety and Tolerability of a Novel Anti-HER2 Antibody-Drug Conjugate (PF-06804103) in Patients with HER2-Expressing Solid Tumors: A Phase 1 Dose-Escalation Study.

Funda Meric-Bernstam, Emiliano Calvo, Keun Seok Lee, Victor Moreno, Yeon Hee Park, Sun Young Rha, Pavani Chalasani, Wei Zhong, Li Zhou, Steven Pirie-Shepherd and 2 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cancer therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03284723 (A Phase 1 Dose Escalation Study Evaluating the Safety and Tolerability of PF-06804103 in Patients With Human Epidermal Growth Factor Receptor 2), which is not on this map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
4.8field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03284723 phase1terminatednot on this map

A Phase 1 Dose Escalation Study Evaluating the Safety and Tolerability of PF-06804103 in Patients With Human Epidermal Growth Factor Receptor 2 (HER2) Positive and Negative Solid Tumors

TypeinterventionalSponsorPfizerRan2017 to 2021Enrolled95ConditionsBreast NeoplasmsArmsPF-06804103, PF-06804103 + Palbociclib +Letrozole
3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Current landscape of sequencing ADCs in metastatic breast cancer.Therapeutic advances in medical oncology · 2025
    Review
  10. Review
  11. Antibody-drug conjugates in gastric cancer: from molecular landscape to clinical strategies.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024
    Review
  12. Review
  13. Research progress on novel antibody drug conjugates in cancer therapy.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024
    Review
  14. Review
  15. Review
  16. Article
  17. The History and Development of HER2 Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2023
    Review
  18. Primary results of ELAINA: a randomized, multicenter, open-label, phase III study of the efficacy and safety of trastuzumab emtansineTranslational breast cancer research : a journal focusing on translational research in breast cancer · 2023
    Article
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 8 institutions in 4 countries.

Funda Meric-BernstamDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0001-6816-6072
Emiliano CalvoSTART Madrid-CIOCC, Centro Integral Oncológico Clara Campal, Madrid, Spain.ORCID 0000-0003-4921-829X
Keun Seok LeeNational Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea.ORCID 0000-0001-5575-836X
Victor MorenoSTART Madrid-FJD, Hospital Fundacion Jimenez Diaz, Madrid, Spain.ORCID 0000-0001-6099-4236
Yeon Hee ParkSamsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.ORCID 0000-0003-4156-9212
Sun Young RhaMedical Oncology, Yonsei Cancer Center, Yonsei University Health System, Seoul, Republic of Korea.ORCID 0000-0002-2512-4531
Pavani ChalasaniUniversity of Arizona Cancer Center, Tucson, Arizona.ORCID 0000-0002-7953-2979
Wei ZhongPfizer Inc., Cambridge, Massachusetts.ORCID 0000-0001-9173-7902
Li ZhouPfizer Inc., San Diego, California.ORCID 0000-0002-9147-9357
Steven Pirie-ShepherdPfizer Inc., New York, New York.ORCID 0000-0002-7173-4576
Abraham C F LeungPfizer Inc., South San Francisco, California.ORCID 0009-0000-8555-1378
Giuseppe CuriglianoEuropean Institute of Oncology, IRCCS, Milano, Italy.ORCID 0000-0003-1781-2518
Pfizer (United States) · USHospital Universitario Fundación Jiménez Díaz · ESNational Cancer Center · KRSamsung Medical Center · KRThe University of Texas MD Anderson Cancer Center · USUniversity Health System · USUniversity of Arizona · USUniversity of Milan · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

PF-06804103 is an anti-HER2 antibody-drug conjugate with auristatin payload. We evaluated its safety, tolerability, and antitumor activity in patients with advanced/unresectable or metastatic breast and gastric cancers. This multicenter, open-label, first-in-human, phase 1 study (NCT03284723) comprised dose escalation (P1) and dose expansion (P2). In P1, adults with HER2+ breast or gastric cancer received PF-06804103 0.15-5.0 mg/kg intravenously once/21 days (Q3W); in P2, patients with HER2+ or HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer received 3.0 or 4.0 mg/kg Q3W. The primary endpoints were dose-limiting toxicities (DLT) and safety (P1), and objective response rate (ORR) assessed using RECIST v1.1 (P2). Ninety-three patients enrolled in P1 (n = 47: HER2+ gastric cancer = 22, HER2+ breast cancer = 25) and P2 [n = 46: HER2+ breast cancer = 19, hormone receptor (HR)+ HER2-low breast cancer = 27] received PF-06804103. Four patients (3.0- and 4.0-mg/kg groups, n = 2 each) had DLTs (mostly Grade 3). Safety and efficacy results showed a dose-response relationship. Adverse events (AE) leading to treatment discontinuation (44/93, 47.3%) included neuropathy (11/93, 11.8%), skin toxicity (9/93, 9.7%), myalgia (5/93, 5.4%), keratitis (3/93, 3.2%), and arthralgia (2/93, 2.2%). Two (2/79, 2.5%) patients (P1, 4.0- and 5.0-mg/kg groups, n = 1 each) achieved complete response; 21 (21/79, 26.6%) achieved partial response. In P2, ORR was higher in HER2+ compared with HR+ HER2-low breast cancer [3.0 mg/kg: 16.7% (2/12) vs. 10.0% (1/10); 4.0 mg/kg: 47.4% (9/19) vs. 27.3% (3/11)]. PF-06804103 demonstrated antitumor activity; however, AEs led to discontinuation in 47.3% of patients. Safety and efficacy were dose-dependent.

Indexed as

Antibodies, MonoclonalAntineoplastic AgentsBreast NeoplasmsImmunoconjugatesOligopeptidesStomach NeoplasmsAdultErb-b2 Receptor Tyrosine KinasesFemaleHumansAntibodies, MonoclonalAntineoplastic AgentsErb-b2 Receptor Tyrosine KinasesImmunoconjugatesOligopeptidesPF-06804103

Identifiers

PMID37420274
PMCPMC10543980
OpenAlexW4383615426

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.