Results from the phase 2b HERIZON-BTC-01 trial show positive efficacy and safety responses in patients with locally advanced, unresectable or metastatic biliary tract cancer.
The use of zanidatamab yielded improved responses in patients with HER2-amplified, locally advanced, unresectable or metastatic biliary tract cancer who received prior gemcitabine therapy, according to results from the phase 2b HERIZON-BTC-01 study (NCT04466891) presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.1
Results were simultaneously published in The Lancet Oncology.2 The confirmed objective response rate (ORR) by independent central review was 41.3% (95% CI, 30.4%-52.8%) in cohort 1, which was comprised of patients with an immunohistochemistry (IHC) score of 2+ or 3+. Cohort 2 included those with an IHC of 0 or 1+.
The median duration of response (DOR) with zanidatamab was 12.9 months (95% CI, 5.95-not estimable [NE]), the median time to first response was 1.8 months, and the median duration of treatment was 5.6 months. The median follow-up time was 12.4 months.
“Zanidatamab demonstrated antitumor activity, including rapid and durable responses in patients with treatment-refractory HER2-positive biliary tract cancer,” Shubham Pant, MD, MBBS, associate professor in the Department of Gastrointestinal Medical Oncology and the Department of Investigational Therapeutics at The University of Texas MD Anderson Cancer Center, said during the presentation of these findings.
A total of 87 patients were enrolled in this trial, with 80 in cohort 1 and 7 in cohort 2. The primary end point was confirmed ORR and key secondary end points were DOR, disease control rate, progression-free survival (PFS), and overall survival (OS). The results presented focused on cohort 1, as cohort 2 was a small sample size and did not have any unique responses or safety signals.
Patients with the aforementioned disease were eligible for treatment if they had available tissue to determine HER2 status and an ECOG performance score of 0 or 1. They also needed to have progressed after prior treatment with a gemcitabine regimen and must not have received prior HER2 therapies to be included.
The median patient age was 64 years, 56.3% were female, and 65% were Asian. A majority of patients had an ECOG performance score of 1 and an IHC of 3+. Overall, 51.3% had gallbladder cancer, 28.8% had intra-hepatic cholangiocarcinoma, and 20% had extra-hepatic cholangiocarcinoma. The median prior lines of therapy were 1.
Patients were given medication to mitigate infusion-related reactions 30 to 60 minutes before the infusion of zanidatamab. Zanidatamab was given at 20 mg/kg on days 1 and 15 of each 28-day cycle.
At the data cutoff, 21% of patients remained on treatment and 26% had discontinued but continued survival follow-up. The most common reason for discontinuation was radiographic progression, which caused 74% of such events. Overall, 37 patients died and 9 withdrew consent.
Responses by independent central review (ICR) included 1.3% of patients having a complete response, 40.0% having a partial response, and 27.5% having stable disease. The disease control rate was 68.8% (95% CI, 57.4%-78.7%). The clinical benefit rate was 47.5% (95% CI, 36.2%-59.0%).
For patients in cohort 1, the confirmed ORR was 12.9 months (95% CI, 6.0-NE) and 49% of patients had a response at data cut-off. In cohort 2, there were no responses to zanidatamab observed.
A post-hoc analysis determined that, of the 21 patients who received PD-1 or PD-L1 inhibitors, 9 had confirmed responses (95% CI, 22%-66%).
In cohort 1, the PFS by ICR was 5.5 months (95% CI, 3.7-7.2) and the rate of OS at 9 months was 69.9% (95% CI, 57.8%-79.1%). The median OS data were still immature at the data cutoff. Additionally, 32 patients had died by data cutoff. In cohort 2, the median PFS was 1.9 months (95% CI, 1.2-not estimable) and the median OS was 5.5 months (95% CI, 1.2-10.1).
Regarding treatment-related adverse effects (TRAEs), 97.5% of patients experienced TRAEs in cohort 1, and 72% had a TRAE relating to zanidatamab. TRAEs which occurred in 10% or more of patients included diarrhea (40.0%) and infusion-related reactions (35.0%).
Serious AEs occurred in 8.8% of patients. There were no grade 4 TRAEs and no treatment-related deaths.
AEs of special interest, and of grade 3 or higher, occurred in 1.3% of patients, 3.8% had a confirmed cardiac event, and 1.3% had non-infectious pulmonary toxicities. Additionally, 7.5% of patients had a select AE of diarrhea.
TRAEs that led to dose delays occurred in 6% of patients, and 3% underwent a dose reduction because of TRAEs. Treatment-emergent AEs of special interest occurred in 97% of patients, all of which resolved. There was 1 instance of a grade 3 infusion-related reaction, which was resolved; it did not preclude treatment with zanidatamab.