# HER2CLIMB-05: A Phase III Study of Tucatinib Versus Placebo in Combination With Trastuzumab and Pertuzumab as First-Line Maintenance Therapy for HER2+ Metastatic Breast Cancer

Source: https://onco.cc/key-papers/paper-her2climb-05-j-clin-oncol-2026/  
OnCo record `paper-her2climb-05-j-clin-oncol-2026` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Published report from the HER2CLIMB-05 trial registered as NCT05132582, in Journal of Clinical Oncology (2026), chosen as the most cited paper whose own text cites the registry id.

## Summary

Purpose: The HER2CLIMB-05 study (ClinicalTrials.gov identifier: NCT05132582) is investigating the efficacy and safety of adding tucatinib to trastuzumab and pertuzumab as first-line (1L) maintenance therapy in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC).

Methods: Patients with centrally confirmed HER2+ MBC without evidence of progression post induction therapy and no or asymptomatic brain metastases (BM) were enrolled. Patients were randomly assigned 1:1 to tucatinib (300 mg) or placebo twice a day combined with trastuzumab/pertuzumab. The primary end point is investigator-assessed progression-free survival (PFS); secondary end points include overall survival (OS), PFS per blinded independent central review, CNS-PFS, and safety.

Results: Between March 2022 and July 2024, 654 patients were randomly assigned to tucatinib (n = 326) and placebo (n = 328) arms. All patients were female (median age, 54 years), 69.3% had de novo MBC, 52.6% were hormone receptor-positive, and 12.4% had presence/history of baseline BM. In this primary analysis, PFS was statistically significantly improved with addition of tucatinib versus placebo (hazard ratio, 0.641 [95% CI, 0.514 to 0.799]; P <.0001; median PFS: 24.9 v 16.3 months); a PFS benefit was seen regardless of the presence/absence of BM or hormone receptor status. OS data remain immature. The most common treatment-emergent adverse events (TEAEs) in the tucatinib arm were diarrhea (72.7%), nausea (33.1%), and elevated liver enzymes (ALT: 28.2%; AST: 25.8%), of which 6.1%, 0.9%, 13.5%, and 7.1%, respectively, were grade ≥3. In the tucatinib arm, 13.5% discontinued tucatinib because of TEAEs.

Conclusion: Tucatinib addition to trastuzumab and pertuzumab demonstrated improvement in PFS with no new safety signals identified and may be an option for 1L maintenance therapy in patients with HER2+ MBC.

Indexed on Europe PMC as PubMed record 41369677 (DOI 10.1200/jco-25-02600). Its abstract cites the registry id NCT05132582, which is how it was matched to this trial; no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Journal of Clinical Oncology
- Year: 2026
- DOI: 10.1200/jco-25-02600
- Authors: Dieras V, Curigliano G, Martin M, et al.
- What it means: This is the paper Europe PMC returns for registry id NCT05132582 with the most citations, so it is the natural first reading for anyone following the HER2CLIMB-05 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Caveats: Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.

## Sources

- J Clin Oncol 2026: https://doi.org/10.1200/jco-25-02600
- PubMed: https://pubmed.ncbi.nlm.nih.gov/41369677/
- Europe PMC: https://europepmc.org/article/MED/41369677
- ClinicalTrials.gov NCT05132582: https://clinicaltrials.gov/study/NCT05132582

## Connected records

- trials: [HER2CLIMB-05](https://onco.cc/trials/her2climb-05/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)

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