Combination treatment with cemiplimab, REGN3767, and chemotherapy appears effective in patients with triple-negative breast cancer (TNBC) and those with hormone receptor (HR)-positive, HER2-negative breast cancer, according to research presented at the San Antonio Breast Cancer Symposium 2022.
Rates of pathologic complete response (pCR) were higher in patients who received cemiplimab plus REGN3767 and chemotherapy than in patients who received chemotherapy alone.
These findings come from the phase 2 I-SPY2 trial (ClinicalTrials.gov Identifier: NCT01042379). The trial uses response-adaptive randomization within biomarker subtypes defined by HR, HER2, and MammaPrint (MP) status to assess the efficacy of novel agents as neoadjuvant therapy in sequence with standard chemotherapy in high-risk breast cancer.
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Patients with HER2-negative disease and tumors measuring at least 2.5 cm were included in this portion of the study evaluating cemiplimab and REGN3767, a LAG-3 antagonist. Patients with HR-positive disease had to be MP high risk as well.
In the cemiplimab-REGN3767 arm, patients were treated with paclitaxel (80 mg/m2 weekly for 12 weeks) and cemiplimab (350 mg) plus REGN3767 (1600 mg; both given every 3 weeks for 4 cycles), followed by doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2, both given every 2-3 weeks for 4 cycles). In the control arm, patients were treated with paclitaxel, doxorubicin, and cyclophosphamide.
The cemiplimab-REGN3767 arm included 76 patients (median age, 47 years; range, 26-78) — 40 with HR-positive disease and 36 with TNBC. The control arm included 350 patients (median age, 48 years; range, 19-80) — 195 with HR-positive disease and 155 with TNBC.
Overall, the estimated pCR rate was 44% in the cemiplimab-REGN3767 arm and 21% in the control arm. This translated to a predictive probability of success in a phase 3 trial of 0.955 for cemiplimab-REGN3767 relative to the control.
Among TNBC patients, the estimated pCR rate was 53% in the cemiplimab-REGN3767 arm and 29% in the control arm, which translated to a predictive probability of success in a phase 3 trial of 0.915.
Among patients with HR-positive disease, the estimated pCR rate was 36% in the cemiplimab-REGN3767 arm and 14% in the control arm, which translated to a predictive probability of success in a phase 3 trial of 0.940.
Immune-related adverse events occurred in 53% of patients in the cemiplimab-REGN3767 arm. These included hypothyroidism (32%), adrenal insufficiency/hypophysitis (21%), type 1 diabetes mellitus (4%), autoimmune hepatitis (3%), pneumonitis (3%), and acute renal failure (3%).
Disclosures: I-SPY2 is sponsored by Quantum Leap Healthcare Collaborative. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Isaacs C, Nanda R, Chien J, et al. Evaluation of anti-PD-1 cemiplimab plus anti-LAG-3 REGN3767 in early-stage, high-risk HER2-negative breast cancer: Results from the neoadjuvant I-SPY 2 trial. Presented at SABCS 2022. December 6-10, 2022. Abstract GS5-03.
