Trastuzumab-strf Gets FDA Approval in Overexpressing Breast and Gastric Cancers

A series of head-to-head trials assessed HLX02 including a phase 1 trial for pharmacokinetic similarity and a global phase 3 trial (NCT03084237). Additionally, HLX02 received prior approvals in Europe and China.

Trastuzumab-strf (HLX02; Hercessi) a monoclonal antibody biosimilar, has been approved as adjuvant therapy for patients with HER2-overexpressing breast cancer, HER2-overexpressing metastatic breast cancer, and HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, according to a press release from Henlius, the developer of the biosimilar.¹

A series of head-to-head trials assessed HLX02 including a phase 1 trial for pharmacokinetic similarity and a global phase 3 trial (NCT03084237). Additionally, HLX02 received prior approvals in Europe and China.

“The approval of [HLX02]—our first biosimilar to be approved in the US—marks an important milestone for Accord BioPharma in our efforts to improve access for patients," said Chrys Kokino, US president of Accord. “Because breast and gastric cancers are among the most common types of cancer and cancer can have a high-cost burden for patients, there is a need to provide these patients with additional treatment options that may be more affordable, such as biosimilars.”

In April 2023, a biologics license application for HLX02 was accepted by the FDA for those in the aforementioned population.² The trial that supported the BLA was conducted at 89 centers across China, the Philippines, Poland, and Ukraine. Patients were randomized 1:1 to receive the biosimilar or the reference drug trastuzumab (Herceptin).

A total 649 patients were enrolled between November 2016 and July 2019.³ The overall response rate (ORR) up to week 24 was 71.3% for HLX02 (n = 324) and 71.4% for EU trastuzumab (n = 325). This showed a difference of –0.1% (95% CI, –7% to 6.9%).

Most commonly, 98.8% of patients in either group experienced at least 1 treatment-emergent adverse effect (TEAE). Additionally, serious TEAEs occurred in 23.8% and 24.9%, respectively. Antidrug antibodies were given to 0.6% of patients in each group.

“Henlius independently developed HLX02 in accordance with the [National Medical products Administration], the European Medicines Agency (EMA), the FDA, and other international biosimilar guidelines. It is Henlius’ first FDA-approved product. Our patient-centered approach has led us to unwaveringly explore high-quality, effective, affordable, and accessible treatment options, and our determination to promote HLX02 in more than 40 markets around the world is Henlius' response to patients' concerns. We look forward to reaching more patients in North America and providing them with more cost-effective access to high-quality biologics.”

The primary end point was ORR at 24 weeks.⁴ Secondary end points included ORR at weeks 6, 12, 18, and 24, duration of response, disease control rate, clinical benefit rate, progression-free survival up to 12 months, and overall survival at 12, 24, and 36 months.

HLX02 was given intravenously 8 mg/kg over 90 minutes at a loading dose of day 1, cycle 1 then 6 mg/kg every 3 weeks for subsequent cycles. Trastuzumab was given at a matched dose. Docetaxel was given at 75 mg/m² on day 2 of cycle 1 and then every 3 weeks on day 1 of each subsequent cycle.

Patients were eligible for treatment if they had histologically or cytologically confirmed adenocarcinoma of the breast, no prior systemic anticancer therapy, and had measurable disease.

Patients were excluded if they had a known brain metastasis or other central nervous system metastasis that is either symptomatic or untreated, participation in another clinical trial within 4 weeks of enrollment, and a history of other malignancies within 5 years.

“Our first FDA-approved biosimilar is an important achievement for our US specialty business, but we’re just getting started. We aspire to deliver one of the deepest portfolios of biosimilars to patients and providers alike, and to help the US health system achieve significant savings,” concluded Binish Chudgar, vice chairman and managing director, Intas Pharmaceuticals. “Our vision to make affordable medicines available forms the bedrock of the company, and this work advances that vision to provide value and promote access for all the key stakeholders we engage along the treatment journey.”

References

1. Henlius Trastuzumab receives FDA approval in the United States. News release. Henlius Biotech, Inc. April 29, 2024. Accessed April 29, 2024. https://www.henlius.com/en/NewsDetails-4563-26.html
2. Accord BioPharma announces U.S. FDA acceptance of biologics license application for proposed biosimilar trastuzumab HLX02. News release. Accord BioPharma. April 5, 2023. Accessed April 29, 2024. https://www.prnewswire.com/news-releases
3. Xu B, Zhang Q, Sun T, et al. Efficacy, safety, and immunogenicity of HLX02 compared with reference trastuzumab in patients with recurrent or metastatic HER2-positive breast cancer: a randomized phase III equivalence trial. BioDrugs. 2021;35(3):337-350. doi:10.1007/s40259-021-00475-w
4. Compare efficacy, safety and immunogenicity of HLX02 and Herceptin in previously untreated HER2 +overexpressing metastatic breast cancer. ClinicalTrials.gov. Accessed April 29, 2024.