Pembrolizumab (pembro) is a new standard of care in chemotherapy (CT) pre-treated patients (pts) with metastatic UC. Nab-paclitaxel demonstrated preliminary activity in advanced UC with an objective response-rate (ORR) as second-line single-agent therapy of 27.7%. In the PEANUT study (NCT03464734) we investigate their combination in advanced UC after CT failure.
In an open-label, single-arm, phase 2 trial, pts receive 200 mg pembro,intravenously (IV), on D1 and 125 mg/m2 IV nab-paclitaxel on D1 and D8, every 3 weeks, until disease progression (PD) or onset of unacceptable toxicity. Key inclusion criteria are: predominant UC histology, failure of ≤2 platinum-based CT for metastatic disease. Response is evaluated by immune-related (ir)RECIST criteria every 2 cycles. Biomarkers include PD-L1 expression with the combined positive score (CPS) and comprehensive genomic profiling on tumor and blood samples (FoundationONE and FoundationLiquid assay). The primary endpoint of the study is the progression-free survival (PFS) according to irRECIST. The target is to detect an improvement in the median PFS from ≤3.0 months (H0) to ≥5.0 months (H1).
Between 01 and 09/2019, PEANUT enrolled 48 pts evaluable for the study endpoint: 26% female, median age 66 y (range 43-78); 70% had failed 1 prior systemic therapy vs 30% 2 prior therapies; 24% had ECOG-performance status (PS) 1; 28% had liver metastases. The median TMB was 6.9 mut/Mb. After median follow-up of 5 months, 18 pts have relapsed (37.5%). The projected median PFS was 7 months (95%CI: 4-not achieved). The confirmed ORR was 50% (95%CI: 35.2-64.8): 18 partial responses and 6 complete responses (12.5%). A clinical benefit was observed in 36 pts (75%). Two pts experienced pseudo-progression. Grade 3 treatment-related adverse events (TRAE) were seen in 6 pts (12.5%). Most common any-grade TRAE included alopecia (91%), asthenia (21.7%), and neutropenia (15%). Neither TMB nor CPS were significantly associated with PFS on univariable analyses, whereas ECOG-PS 1 (p=0.002) and liver metastases (0.02) were significantly negative predictors of PFS on multivariable analyses. 7/8 pts with PI3KCA mutations in matched tumor/blood samples had an objective response (87.5%).
Preliminary results from PEANUT study demonstrated a promising PFS and a clinically meaningful ORR of pembrolizumab and nab-paclitaxel combination as II-III line therapy of advanced UC. Updated data, including mature PFS, duration of response and biomarkers will be presented.