Bevacizumab Biosimilar HD204 Meets Primary End Point in Phase 3 NSCLC Trial

A proposed bevacizumab (Avastin) biosimilar, HD204, met the primary end point of the phase 3 SAMSON-II study (NCT03390686) in patients with advanced nonsquamous non–small cell lung cancer (NSCLC).¹ The topline results showed clinical equivalence in overall response rate (ORR) at week 18 between HD204 and the reference bevacizumab, with a safety profile consistent with the established bevacizumab experience.

Primary Efficacy Results

The ORR at week 18 was 48.7% in the HD204 arm vs 46.5% in the reference bevacizumab arm. The risk ratio was 1.047 (95% CI, 0.86-1.27), and the risk difference was 0.022 (95% CI, −0.07-0.11), with both point estimates and confidence intervals falling within the prespecified equivalence margins. Prestige Biopharma, the sponsor, stated that the predefined equivalence criteria were satisfied.

"These results illustrate the increasing precision with which biosimilarity can be established through advanced analytical and clinical [pharmacokinetic (PK)] studies," said Lisa Park, PhD, CEO of Prestige Biopharma, in a news release. "Our experience with HD204 supports the view that well-designed development programs can reliably anticipate clinical performance, enabling more focused and efficient biosimilar development. By reducing unnecessary clinical burden, such advances can accelerate patient access to high-quality biologic medicines and support more sustainable healthcare systems worldwide."

Secondary efficacy end points were supportive. Comparable ORR was observed at week 12, and no statistically significant differences were identified in time-to-event outcomes, including progression-free survival and overall survival, between the 2 treatment groups.

Study Design

SAMSON-II was a randomized, double-blind, parallel-group, multicenter phase 3 equivalence study conducted across 91 centers in 15 countries. A total of 625 adult patients with metastatic or recurrent nonsquamous NSCLC were enrolled and randomized 1:1 to receive HD204 or reference bevacizumab in combination with standard carboplatin-paclitaxel chemotherapy.²

The choice of nonsquamous NSCLC as the study population reflects regulatory guidance favoring sensitive clinical populations for biosimilar efficacy comparisons, given that bevacizumab in combination with carboplatin and paclitaxel is a well-established first-line regimen in this setting with a reliably measurable response rate end point.¹

Safety and Tolerability

The safety profile of HD204 was consistent with the known bevacizumab profile. Treatment-related adverse events (AEs) were reported in 33.9% of patients in the HD204 arm and 34.4% in the reference bevacizumab arm. Treatment-related serious AEs occurred in 5.2% of HD204-treated patients and 8.3% of reference bevacizumab-treated patients. No new or unexpected safety signals were identified in either treatment group.

Known bevacizumab-associated AEs of clinical relevance (including hypertension, proteinuria, arterial thromboembolic events, wound healing complications, and hemorrhage) require ongoing monitoring in clinical practice, as reflected in prescribing information for the reference product and approved biosimilars.

Context Within the HD204 Development Program

The SAMSON-II results build on prior comparative PK data from the phase 1 SAMSON-I study (NCT03390673), a randomized, double-blind, 3-way parallel-group single-dose study in which 119 healthy male patients received HD204, EU-sourced bevacizumab, or US-sourced bevacizumab.³ In that study, the 90% confidence intervals for the geometric mean ratios of area under the concentration–time curve for all 3 pairwise comparisons were within the prespecified equivalence interval of 80% to 125%, demonstrating equivalent PK profiles across all 3 products. No immunogenicity signals were observed for HD204 in that population.¹

Prestige Biopharma characterized the SAMSON-II clinical outcomes as consistent with this high degree of analytical and PK similarity previously demonstrated between HD204 and the reference product. The sponsor indicated it intends to advance regulatory submissions for HD204 based primarily on the strength of the analytical and clinical PK program, while contributing the phase 3 data to the broader scientific evidence base for biosimilar development methodology.

REFERENCES

1. Prestige Biopharma Announces Positive Topline Results from Comparative SAMSON-II Study for HD204, a Potential Biosimilar to Avastin (bevacizumab). News release. Prestige Biopharma. March 24, 2026. Accessed March 25, 2026. https://tinyurl.com/55ajcmmd

2. A Trial to Compare the Efficacy, Safety, Pharmacokinetics and Immunogenicity of HD204 to Avastin® in Advanced Non-squamous Non-small Cell Lung Cancer Patients. ClinicalTrials.gov. Updated May 31, 2025. Accessed March 25, 2026. https://clinicaltrials.gov/study/NCT03390686

3. To Demonstrate Equivalent Pharmacokinetic Properties of HD204 and Bevacizumab (Avastin®) in Healthy Male Subjects. ClinicalTrials.gov. Updated November 19, 2024. Accessed March 25, 2026. https://clinicaltrials.gov/study/NCT03390673