Researchers found encouraging findings from combination therapy with zanidatamab and docetaxel as first-line therapy in patients with advanced HER2-positive breast cancer, based on a phase 1b/2 study presented at the ASCO 2022 Annual Meeting. 

Preliminary results showed antitumor activity in this patient population, with a manageable safety profile. Zanidatamab is a novel HER2-targeted bispecific antibody that binds to two distinct extracellular domains of HER2.  

The researchers analyzed data from two cohorts of patients participating in an ongoing open-label study (NCT04276493) designed to evaluate combination therapy with zanidatamab and docetaxel as first-line therapy in adult females with advanced HER2+ breast cancer who may have received prior neoadjuvant/adjuvant treatment.  

In one group, patients were treated with 30 mg/kg of intravenous zanidatamab plus 75 mg/m2 IV docetaxel every 3 weeks (cohort A); participants in the second group (cohort B) received 1800 mg IV zanidatamab, again with 75 mg/m2 IV docetaxel every 3 weeks.  

At the November 2021 data cutoff, 25 patients (median age 57 years) were available for analysis, 11 in cohort A and 14 in cohort B. After a median follow-up period of 7.0 months (range 1.1-17.4 months), 16 (64.0%) patients remained on treatment. Over this time, the median number of treatment cycles was 10 (range: 2-20). 

According to principal investigator Keun-Seok Lee, MD, PhD, staff physician at the center for breast cancer from the National Cancer Center, Korea, and colleagues, the confirmed ORR among 22-efficacy evaluable patients was 86.4%, (n = 19/22), 88.9% among patients in cohort A (n = 8/9) and 84.6% (n = 11/13) in cohort B. The confirmed disease control rate was 90.9%, (n = 20/22), 88.9% in cohort A patients (n = 8/9) and 92.3% in cohort B patients (n = 12/13).  

Analyses of confirmed best overall response found complete response in 1 out of 22 patients (4.5%) (1/9, 11.1% cohort A; 0/13, 0.0% cohort B), partial response in 18/22 patients (81.8%) (7/9, 77.8% and 11/13, 84.6%, respectively), and stable disease in 1/22 patients (4.5%) (0/9, 0.0%; 1/13, 7.7%). The 6-month PFS rate was 90.9%; progressive disease was observed in only 2 of the 22 evaluable participants.  

With respect to tolerability, all patients experienced treatment-emergent adverse events of at least grade 1; 68.0% (n = 17) experienced treatment-emergent adverse events of at least grade 3. Similarly, 92.0%  (n = 23) had treatment-related adverse events; 68.0% (n = 17) were at least grade 3. While one serious treatment-related adverse event led to treatment discontinuation, none led to death. 

The authors seemed encouraged by the trial’s preliminary findings. 

“Zanidatamab and docetaxel combination demonstrated antitumor activity in first-line therapy for advanced HER2+ breast cancer,” they wrote, “with a manageable safety profile.” 

Reference: 
https://meetinglibrary.asco.org/embargo/record/210373/abstract 

Disclosures: Authors declared financial ties to drugmakers. See full study for details. The study was funded by BeiGene. 
Photo Credit: Getty Images, Pixabay 

By Michael Vlessides, MD /alert Contributor