A phase 2 study presented at the 2024 San Antonio Breast Cancer Symposium (SABCS) indicates that a combination of tislelizumab, sitravatinib, and nab-paclitaxel demonstrates clinically meaningful responses and progression-free survival (PFS) in patients with previously untreated, locally advanced or recurrent triple-negative breast cancer (TNBC). The SPARK trial (NCT04734262) suggests that CD8 status may serve as a predictive biomarker for treatment efficacy with this tislelizumab-based regimen.
Efficacy Outcomes
The triplet combination yielded an objective response rate (ORR) of 75.7% (95% CI, 58.8%-88.2%) per RECIST v1.1 criteria. The data showed complete responses in 7 patients (18.9%), partial responses in 21 (56.8%), stable disease in 8 (21.6%), and progressive disease in 1 (2.7%). The disease control rate (DCR) was 97.3% (95% CI, 85.8%-99.9%).
The median PFS among all evaluable patients was 10.6 months (95% CI, 7.9-15.8). Patients with CD8-positive disease had a median PFS of 15.8 months, while those with CD8-negative disease had a median PFS of 9.1 months. For patients with a PD-L1 combined positive score (CPS) of 1 or higher, the median PFS was 12.3 months, compared to 10.6 months for those with a PD-L1 CPS of less than 1.
The median overall survival (OS) was not reached at the time of analysis. The 1-year OS rate was 91.0% (95% CI, 74.6%-97.0%).
Investigator Comments
"The triplet combination of [tislelizumab plus sitravatinib and nab-paclitaxel] demonstrated clinically meaningful ORR and PFS with acceptable safety profile as first-line treatment for patients with untreated locally recurrent or metastatic TNBC," wrote Xiyu Liu, from Fudan University Shanghai Cancer Center in Shanghai, China, and coauthors. "Notably, patients with [CD8-positive] expression achieved impressive PFS, indicating the CD8 status may serve as a potential biomarker for predicting treatment efficacy. Continued follow-up is being conducted to assess long-term survival and safety."
Trial Design and Patient Characteristics
The SPARK trial included three cohorts of patients with locally recurrent or metastatic TNBC. Cohort C (n = 35), whose findings were reported in this poster, included patients without prior therapy for advanced TNBC who received sitravatinib at 70 mg orally once daily, tislelizumab at 200 mg intravenously every 3 weeks, and nab-paclitaxel on days 1 and 8 of each cycle every 3 weeks.
The primary endpoints of the trial were ORR across all cohorts and grade 3 or higher treatment-related adverse events (TRAEs) in cohort B. Secondary endpoints included duration of response, DCR, PFS, 1-year OS rate, patient-reported outcomes, and safety. Eligible patients were 18 years or older with locally recurrent or metastatic TNBC, an ECOG performance status of 0 or 1, and measurable lesions per RECIST v1.1 guidelines.
Among the 37 evaluable patients in cohort C, the median age was 49 years (range, 28-73), and most patients had an ECOG performance status of 0 (67.6%). A majority of patients had prior neoadjuvant or adjuvant therapy (56.8%), 0 to 2 metastases (70.3%), and CD8-negative disease (54.1%).
Safety Profile
TRAEs of any grade occurred in 97.3% of patients, with grade 3 or higher events reported in 43.2%. Serious adverse events (AEs) occurred in 29.7% of patients, and no new safety signals were identified. The most common any-grade TRAEs included increased alanine aminotransferase (86.5%), white blood cell count decreases (75.7%), increased aspartate aminotransferase (73.0%), increased blood thyroid stimulating hormones (73.0%), and swollen palmar and plantar syndrome (54.1%).
