Intravenous Injections of Zanidatamab-Hrii Receives FDA Accelerated Approval for IHC+ BTC

The FDA granted an accelerated approval to zanidatamab-hrii (Ziihera; Jazz Pharmaceuticals) for the treatment of adults with previously treated unresectable or metastatic HER2+ (IHC+) biliary tract cancer (BTC) as detected by an FDA-approved test. The treatment showed positive objective response rate (ORR) and duration of response (DOR) in patients. Continued approval for this indication will be depending on description and verification of clinical benefits in a confirmatory phase 3 trial, HERIZON-BTC-302 (NCT06282575).¹

Zanidatamab is currently undergoing investigation in a number of tumor types, including gastroesophageal adenocarcinomas and metastatic breast cancer. In patients with previously treated unresectable or metastatic IHC 3+ BTC, the treatment is administered via a 50 mg/mL intravenous (IV) injection. The accelerated approval comes after data from the HERIZON-BTC-01 clinical trial (NCT04466891).¹

“BTC is a devastating disease with a poor prognosis and 5-year survival rates under 5% in the metastatic setting. Patients with unresectable or metastatic IHC 3+ BTC have had a high unmet need with limited treatment options and few approved therapies," Rob Iannone, MD, MSCE, executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals, said in a news release. "The approval of [zanidatamab], which previously received [a] breakthrough therapy designation from the FDA for this indication, is an important advance and offers the first and only dual HER2-targeted bispecific antibody and chemotherapy-free treatment for patients living with BTC.”¹

The open-label, global phase 2b clinical trial HERIZON-BTC-01 (NCT04466891) enrolled a total of 87 patients with HER2-amplified, locally advanced unresectable or metastatic BTC (eg, gallbladder cancer, intra-/extra-hepatic cholangiocarcinoma) who received prior gemcitabine-containing therapy, of which 62 had HER2 IHC 3+ BTC. Patients were assigned to 1 of 2 groups depending on their tumor IHC status: cohort 1 (n = 80) consisted of patients who were IHC 2+/3+, and cohort 2 (n = 7) included patients who were IHC 0/1+. Regardless of their disease state or the cohort they were assigned to, all patients received 20 mg/kg of IV zanidatamab monotherapy every 2 weeks.^1-3

The primary outcome measure was ORR, which was assessed up to 34 months. Secondary outcome measures included DOR, progression-free survival (PFS), overall survival (OS), and incidence of adverse events (AEs), which were assessed up to 34 months. Disease control rate was also evaluated, and this was assessed at 24 weeks and up to 34 months.^1,2

According to the findings, patients treated with zanidatamab achieved a 52% ORR and an estimated median DOR of about 14.9 months. In the trial, serious AEs occurred in about 53% of patients who received zanidatamab, which included biliary obstruction (15%), biliary tract infection (8%), sepsis (8%), pneumonia (5%), diarrhea (3.8%), gastric obstruction (3.8%), and fatigue (2.5%). The most common AEs consisted of diarrhea, infusion-related reaction, abdominal pain, and fatigue. There was 1 fatal occurrence of hepatic failure.^1,3

Further, the confirmatory, global, randomized phase 3 trial HERIZON-BTC-302 (NCT06282575) is ongoing and evaluating zanidatamab in confirmation with standard of care compared with standard of care therapy alone in the first-line setting. Patients enrolled in the trial include those with HER2+ BC. The primary outcome measure is PFS and secondary outcomes include OS, confirmed ORR, DOR, and the number of treatment-emergent AEs.^1,4

"Metastatic BTC places a significant burden on patients, affecting their quality of life and their emotional and mental well-being, as well as that of their families," said Stacie Lindsey, CEO and founder of the Cholangiocarcinoma Foundation, in the news release. "The approval of [zanidatamab] offers a promising treatment option. It provides patients and their loved ones the possibility of more time together and an improved quality of life, which is invaluable for the entire BTC community."¹

REFERENCES

1. Jazz Pharmaceuticals Announces U.S. FDA Approval of Ziihera (zanidatamab-hrii) for the Treatment of Adults with Previously Treated, Unresectable or Metastatic HER2-positive (IHC 3+) Biliary Tract Cancer (BTC). News release. PR Newswire. November 20, 2024. Accessed November 21, 2024. https://www.prnewswire.com/news-releases/jazz-pharmaceuticals-announces-us-fda-approval-of-ziihera-zanidatamab-hrii-for-the-treatment-of-adults-with-previously-treated-unresectable-or-metastatic-her2-positive-ihc-3-biliary-tract-cancer-btc-302312216.html

2. A Study of ZW25 (Zanidatamab) in Subjects With Advanced or Metastatic HER2-Amplified Biliary Tract Cancers (HERIZON-BTC-01). ClinicalTrials.gov identifier: NCT04466891. Updated August 21, 2024. Accessed November 21, 2024. https://clinicaltrials.gov/study/NCT04466891

3. Harding JJ, Fan J, Oh D-Y, et al. Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study. Lancet Oncology. 2023;24(7):772-782. doi:10.1016/S1470-2045(23)00242-5

4. Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy for Advanced HER2-positive Biliary Tract Cancer. ClincialTrials.gov identifier: NCT06282575. Updated November 12, 2024. Accessed November 21, 2024. https://clinicaltrials.gov/study/NCT06282575