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ZIIHERA was evaluated in the largest Phase 2b clinical trial to date for patients with HER2-positive BTC1*

HERIZON-BTC-01 is a global, multicenter, single-arm, Phase 2b trial evaluating ZIIHERA in 80 PREVIOUSLY TREATED patients with HER2-positive BTC.1,2†

Efficacy population:
62 patients with HER2-positive (IHC 3+) BTC2

Safety population:
80 patients with HER2-positive BTC (IHC 2+ or 3+, ISH+)1,2

28-day cycles1

ZIIHERA 20 mg/kg IV
administered until disease
progression or unacceptable toxicity2

Day 1

Day 15

Every 8 weeks:
CT/MRI to assess tumors1

Primary Endpoint2

  • ORR by ICR‡

Select Secondary Endpoints1,3

  • DOR by ICR
  • Frequency of
    SARs and deaths
  • OS
  • PFS by ICR
  • Frequency and
    severity of ARs

Key Eligibility Criteria

  • ≥18 years of age1
  • Progression after treatment with a gemcitabine-containing regimen1
  • Pathologically confirmed unresectable or metastatic gallbladder cancer, intrahepatic cholangiocarcinoma, or extrahepatic cholangiocarcinoma1,2§
  • HER2-positive (IHC 2+ or 3+) centrally confirmed with tissue biopsy; all patients were tested with both IHC and ISH1,2
  • ECOG PS of 0-11
  • No prior HER2-targeted therapies1

*Inclusive only of FDA-approved second-line treatments. Current as of 11/2024.4

†Patients with HER2-positive BTC (confirmed by central laboratory ISH) were enrolled into prospectively defined cohorts based on HER2 IHC score. Cohort 1 included 62 patients with HER2 IHC 3+. All 80 patients were included in the safety analyses.1,2

‡Assessments were performed by ICR per RECIST v1.1.2

§Excludes ampullary.3

 

AR=adverse reaction; BTC=biliary tract cancer; CT=computerized tomography; DOR=duration of response; ECOG PS=Eastern Cooperative Oncology Group performance status; FDA=Food and Drug Administration; HER2=human epidermal growth factor receptor 2; ICR=independent central review; IHC=immunohistochemistry; ISH=in situ hybridization; IV=intravenous; MRI=magnetic resonance imaging; ORR=objective response rate; OS=overall survival; PFS=progression-free survival; RECIST=Response Evaluation Criteria in Solid Tumors; SAR=serious adverse reaction.

HERIZON-BTC-01: patient demographics and baseline characteristics

Patients with IHC 3+ who received ZIIHERA (N=62)2,5
Age, years
Median (range)64 (38-79)
Sex
Female55%
Male45%
Race
Asian61%
White31%
American Indian/Alaskan Native2%
Unknown/Not Reported6%
ECOG PS
032%
168%
BTC subtype
Gallbladder cancer53%
Intrahepatic cholangiocarcinoma27%
Extrahepatic cholangiocarcinoma19%
Baseline disease stage
Stage III13%
Stage IV87%
Prior lines of therapy in the metastatic setting
Median (range)1 (1-7)
Regimen received
Gemcitabine-based100%
CISGEM76%
Fluoropyrimidine-based||32%
PD-1/PD-L1 inhibitor26%

41% of patients had received ≥2 prior lines of therapy before treatment with ZIIHERA2

Patients were counted at most only once under each regimen type received and might be counted in multiple categories.5

||Excluded regimens in combination with gemcitabine.5

 

CISGEM=cisplatin and gemcitabine; PD-1=programmed cell death protein 1; PD-L1=programmed death ligand 1.

 
Next:
Results

INDICATION

ZIIHERA (zanidatamab-hrii) 50 mg/mL for Injection for IV is indicated for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

IMPORTANT SAFETY INFORMATION AND INDICATION

WARNING: EMBRYO-FETAL TOXICITY
Exposure to ZIIHERA during pregnancy can cause embryo-fetal harm. Advise patients of the risk and need for effective contraception.

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity

ZIIHERA can cause fetal harm when administered to a pregnant woman. In literature reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death.

Verify the pregnancy status of females of reproductive potential prior to the initiation of ZIIHERA. Advise pregnant women and females of reproductive potential that exposure to ZIIHERA during pregnancy or within 4 months prior to conception can result in fetal harm. Advise females of reproductive potential to use effective contraception during treatment with ZIIHERA and for 4 months following the last dose of ZIIHERA.

Left Ventricular Dysfunction

ZIIHERA can cause decreases in left ventricular ejection fraction (LVEF). LVEF declined by >10% and decreased to <50% in 4.3% of 233 patients. Left ventricular dysfunction (LVD) leading to permanent discontinuation of ZIIHERA was reported in 0.9% of patients. The median time to first occurrence of LVD was 5.6 months (range: 1.6 to 18.7). LVD resolved in 70% of patients.

Assess LVEF prior to initiation of ZIIHERA and at regular intervals during treatment. Withhold dose or permanently discontinue ZIIHERA based on severity of adverse reactions.

The safety of ZIIHERA has not been established in patients with a baseline ejection fraction that is below 50%.

Infusion-Related Reactions

ZIIHERA can cause infusion-related reactions (IRRs). An IRR was reported in 31% of 233 patients treated with ZIIHERA as a single agent in clinical studies, including Grade 3 (0.4%), and Grade 2 (25%). IRRs leading to permanent discontinuation of ZIIHERA were reported in 0.4% of patients. IRRs occurred on the first day of dosing in 28% of patients; 97% of IRRs resolved within one day.

Prior to each dose of ZIIHERA, administer premedications to prevent potential IRRs. Monitor patients for signs and symptoms of IRR during ZIIHERA administration and as clinically indicated after completion of infusion. Have medications and emergency equipment to treat IRRs available for immediate use.

If an IRR occurs, slow, or stop the infusion, and administer appropriate medical management. Monitor patients until complete resolution of signs and symptoms before resuming. Permanently discontinue ZIIHERA in patients with recurrent severe or life-threatening IRRs.

Diarrhea

ZIIHERA can cause severe diarrhea.

Diarrhea was reported in 48% of 233 patients treated in clinical studies, including Grade 3 (6%) and Grade 2 (17%). If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Withhold or permanently discontinue ZIIHERA based on severity.

ADVERSE REACTIONS

Serious adverse reactions occurred in 53% of 80 patients with unresectable or metastatic HER2-positive BTC who received ZIIHERA. Serious adverse reactions in >2% of patients included biliary obstruction (15%), biliary tract infection (8%), sepsis (8%), pneumonia (5%), diarrhea (3.8%), gastric obstruction (3.8%), and fatigue (2.5%). A fatal adverse reaction of hepatic failure occurred in one patient who received ZIIHERA.

The most common adverse reactions in 80 patients with unresectable or metastatic HER2-positive BTC who received ZIIHERA (≥20%) were diarrhea (50%), infusion-related reaction (35%), abdominal pain (29%), and fatigue (24%).

USE IN SPECIFIC POPULATIONS

Pediatric Use

Safety and efficacy of ZIIHERA have not been established in pediatric patients.

Geriatric Use

Of the 80 patients who received ZIIHERA for unresectable or metastatic HER2-positive BTC, there were 39 (49%) patients 65 years of age and older. Thirty-seven (46%) were aged 65-74 years old and 2 (3%) were aged 75 years or older.

No overall differences in safety or efficacy were observed between these patients and younger adult patients.

Please click here to see the full Prescribing Information, including BOXED Warning.

References: 1. Harding JJ, Fan J, Oh DY, 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 Oncol. 2023;24(7):772-782. doi:10.1016/S1470-2045(23)00242-5 2. ZIIHERA (zanidatamab-hrii) Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc. 2024. 3. Pant S, Fan J, Oh DY, et al. Results from the pivotal phase 2b HERIZON-BTC-01 study: zanidatamab in previously-treated HER2-amplified biliary tract cancer (BTC). Presented at: the annual meeting of the American Society of Clinical Oncology; June 2-6, 2023; Illinois, USA. 4. ten Haaft BH, Pedregal M, Prato J, Klümpen HJ, Moreno V, Lamarca A. Revolutionizing anti-HER2 therapies for extrahepatic cholangiocarcinoma and gallbladder cancer: current advancements and future perspectives. Eur J Cancer. 2024;199:113564. doi:10.1016/j.ejca.2024.113564. 5. Data on file. Jazz Pharmaceuticals, Inc.