Early Evidence Supports KM118 as a Biosimilar to Reference Pertuzumab

In HER2-positive breast cancer, pertuzumab remains a cornerstone therapy, but its price has limited access in some markets, underscoring the need for biosimilar alternatives that can maintain clinical confidence while expanding affordability.¹

A new study confirms KM118, a proposed biosimilar to pertuzumab, shows pharmacokinetic similarity and safety, paving the way for affordable HER2-positive breast cancer treatments. | Image credit: Romolo Tavani - stock.adobe.com

KM118, a proposed biosimilar to reference pertuzumab (Perjeta; Genentech, Inc.), was evaluated in a phase 1 pharmacokinetic study designed to support regulatory approval in China.² The study, published in Annals of Medicine, was conducted to determine whether KM118 demonstrated pharmacokinetic similarity to the reference product and to assess its safety, tolerability, and immunogenicity in healthy participants, key requirements under international biosimilar development guidelines.

The randomized, double-blind, single-center, parallel-group study enrolled 100 healthy adult men in China. Participants were randomly assigned in a 1:1 ratio to receive a single 420-mg intravenous dose of either KM118 or reference pertuzumab. This fixed dose reflected established pertuzumab dosing and aligned with prior pharmacokinetic research. Blood samples were collected through 84 days after administration to characterize drug exposure, whereas safety and immunogenicity were monitored throughout the study period.

All participants were male, with a mean age of approximately 32 years and a mean body mass index of 22.9 kg/m². Most participants identified as Han Chinese, with a small number from other ethnic backgrounds. Individuals with clinically significant medical conditions, prior monoclonal antibody exposure, or evidence of pre-existing anti-drug antibodies were excluded, ensuring a relatively homogeneous and healthy study population suitable for detecting pharmacokinetic differences.

The primary pharmacokinetic endpoint was the area under the concentration–time curve from time 0 to the last measurable concentration (AUC₀–t). Biosimilarity was prespecified as a 90% confidence interval for the geometric mean ratio between test and reference products falling within the standard equivalence range of 80% to 125%. Secondary endpoints included maximum concentration (Cmax), AUC extrapolated to infinity (AUC₀–∞), and additional pharmacokinetic parameters.

Results showed closely aligned pharmacokinetic profiles between KM118 and reference pertuzumab. The geometric mean AUC₀–t was 74,465.82 ng·h/mL in participants receiving KM118 and 69,097.83 ng·h/mL in those receiving reference pertuzumab. The geometric mean ratio for AUC₀–t was 107.07%, with a 90% confidence interval of 99.92% to 114.72%, meeting the predefined biosimilarity criteria. Similarly, the confidence intervals for Cmax and AUC₀–∞ also fell within the accepted equivalence range, supporting overall pharmacokinetic similarity between the products.

Safety findings were consistent with expectations for pertuzumab exposure in healthy individuals. Most adverse events were grade 1 or 2 in severity, and no serious adverse events or grade 3 or higher events were reported. The most frequently observed events included laboratory abnormalities such as elevated triglycerides or uric acid, along with diarrhea and upper respiratory tract infections. The incidence and pattern of adverse events were comparable between treatment groups, suggesting no new safety signals associated with the biosimilar candidate.

Immunogenicity analyses showed similar rates of anti-drug antibody development between the 2 groups. Approximately 28% of participants tested positive for antidrug antibodies at the final assessment, with comparable proportions in the KM118 and reference arms. Neutralizing antibodies were rare, detected in only 1 participant. Although participants who developed antibodies had somewhat lower drug exposure and shorter half-lives, these findings were consistent with prior pertuzumab studies and did not differ meaningfully by treatment group.

The authors noted several limitations relevant to interpretation and payer decision-making. The study population included only healthy male participants, which limited generalizability to women and to individuals with breast cancer who may have comorbidities or receive combination therapies. In addition, the phase 1 design focused on pharmacokinetics rather than clinical efficacy, necessitating confirmatory phase 3 trials in patients with HER2-positive breast cancer to establish therapeutic equivalence.

Overall, the findings demonstrated pharmacokinetic biosimilarity between KM118 and reference pertuzumab, with comparable safety and immunogenicity profiles in healthy adults. For managed care stakeholders, these results represented an early but important step toward expanding biosimilar competition in the HER2-targeted therapy space, with the potential to improve access and moderate oncology drug spending pending further clinical confirmation.

References

1. Jeremias S. FDA approves poherdy: first interchangeable biosimilar to Perjeta. The Center for Biosimilars^®️. November 18, 2025. Accessed January 28, 2026. https://www.centerforbiosimilars.com/view/fda-approves-poherdy-first-interchangeable-biosimilar-to-perjeta
2. Li Y, Wang Y, Yang C, Zhao N, Wang X. A phase I, randomized, double-blind, parallel, single-dose pharmacokinetic study to evaluate the biosimilarity of KM118 (proposed pertuzumab biosimilar) with reference pertuzumab (Perjeta) in healthy male subjects. Ann Med. 2025;57(1):2523561. doi:10.1080/07853890.2025.2523561