Trial results for atezolizumab in combination with other agents for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer were posted on ClinicalTrials.gov on 2025-11-10. The study showed that the triplet combination of fulvestrant + atezolizumab + abemaciclib achieved an objective response rate of 26.3% and a median progression-free survival of 6.28 months.
Background
The study investigated atezolizumab in combination with other agents for participants with inoperable locally advanced or metastatic HR-positive, HER2-negative breast cancer. These participants had previously progressed during or following treatment with a cyclin-dependent kinase (CDK) 4/6 inhibitor, such as palbociclib, ribociclib, or abemaciclib, in the first- or second-line setting.
Trial design
The study, identified as NCT03280563, was a Phase 1/Phase 2 trial that enrolled 144 participants with HR-positive, HER2-negative breast cancer. The study was designed to evaluate several immunotherapy-based combination treatments. During Stage 1, participants were randomized to receive either fulvestrant (control) or various atezolizumab-containing doublet or triplet combinations, including fulvestrant + atezolizumab, fulvestrant + atezolizumab + ipatasertib, atezolizumab + ipatasertib, atezolizumab + entinostat, and fulvestrant + atezolizumab + abemaciclib.
Key results
The trial evaluated objective response rates (ORR) and progression-free survival (PFS) across various treatment arms in Stage 1:
- For "Percentage of Participants With Objective Response":
- Fulvestrant Control: 10.0%
- Fulvestrant + Atezolizumab: 10.0%
- Fulvestrant + Atezolizumab + Ipatasertib: 26.9%
- Atezolizumab + Ipatasertib: 16.7%
- Atezolizumab + Entinostat: 6.7%
- Fulvestrant + Atezolizumab + Abemaciclib: 26.3%
- For "Progression-free Survival (PFS)":
- Fulvestrant Control: Median 1.95 months
- Fulvestrant + Atezolizumab: Median 3.15 months
- Fulvestrant + Atezolizumab + Ipatasertib: Median 5.86 months
- Atezolizumab + Ipatasertib: Median 2.28 months
- Atezolizumab + Entinostat: Median 1.82 months
- Fulvestrant + Atezolizumab + Abemaciclib: Median 6.28 months
Key analyses comparing objective response rates to Fulvestrant Control included:
- Difference in ORR for Fulvestrant + Atezolizumab: 0.0 (95.0% CI: -21.14 to 21.14)
- Difference in ORR for Fulvestrant + Atezolizumab + Ipatasertib: 16.92 (95.0% CI: -9.03 to 42.88)
- Difference in ORR for Atezolizumab + Ipatasertib: 6.67 (95.0% CI: -36.76 to 50.09)
- Difference in ORR for Atezolizumab + Entinostat: -3.33 (95.0% CI: -27.39 to 20.73)
- Difference in ORR for Fulvestrant + Atezolizumab + Abemaciclib: 16.32 (95.0% CI: -6.71 to 39.34)
The Hazard Ratio (HR) for PFS comparing Fulvestrant + Atezolizumab to Fulvestrant Control was 0.91 (95.0% CI: 0.5 to 1.66).
What this means
The results indicate that certain atezolizumab-containing triplet combinations, particularly with ipatasertib or abemaciclib, demonstrated higher objective response rates and longer median progression-free survival compared to fulvestrant alone or fulvestrant + atezolizumab in patients with previously treated HR-positive, HER2-negative breast cancer. These findings suggest that further investigation into these specific combination strategies may be warranted for this challenging patient population.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03280563, titled "A Study of Multiple Immunotherapy-Based Treatment Combinations in Hormone Receptor (HR)-Positive Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer," were posted on 2025-11-10 on clinicaltrials.gov.