The I-SPY2 platform trial evaluated adding dual checkpoint blockade — cemiplimab (anti-PD-1) plus fianlimab (anti-LAG-3) — to standard neoadjuvant paclitaxel followed by doxorubicin/cyclophosphamide (PCF) vs. historical control in 78 patients with early-stage (II/III), ERBB2-negative, high-risk breast cancer (HR+ and triple-negative subtypes), enrolled February 2020–December 2021.
PCF graduated in all clinical signatures: pCR rates were 44% vs 21% (all ERBB2-negative), 53% vs 29% (triple-negative), and 36% vs 14% (HR+/ERBB2-negative) compared to control. Adrenal insufficiency/hypophysitis occurred in 21% of participants (11% grade 3–4).
- Small intervention arm (n=78) compared to a larger historical control (n=350), introducing potential selection bias. - Historical control design limits direct causal inference vs. a concurrent randomized comparator. - Full text not yet available (embargoed until 2027); biomarker and survival data may be incomplete in the abstract.
Dual PD-1 + LAG-3 blockade with neoadjuvant chemotherapy roughly doubles pCR rates in ERBB2-negative breast cancer, especially in ImPrint-positive patients — but clinicians should monitor closely for delayed adrenal insufficiency and hypophysitis, which affected 1 in 5 patients.
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