KEY TAKEAWAYS
- The PAPMET2 phase 2 trial aimed to assess the comparative efficacy of cabo/atezo and cabo alone in patients with PRCC.
- The primary endpoint is the comparison of PFS between cabo vs. cabo/atezo.
- The prospective outcomes include stool microbiome, genomic/transcriptomic analysis, and updated enrollment and site activation status.
The role of immune therapy has yet to be fully established in papillary renal cell carcinoma (PRCC). The S1500 (PAPMET) clinical trial established single-agent cabozantinib (cabo) as the standard of care for PRCC (PMID 33592176), with a median progression-free survival (PFS) of 9.0 months compared to 5.6 months with sunitinib. Trials have shown the activity of PD-(L)1 antagonist as monotherapy (PMID 33529058) or in combination with targeted therapy (PMID 34491815).
In a single-arm study of cabo/nivolumab, the median PFS was 12.5 months (PMID 35298296). There are no prior randomized studies of immune therapy in PRCC. Single-arm trials often overestimate the true effect size (PMID 31218346).
Real world data suggests that combination therapy is not more effective than single-agent treatment (PMID 36610815). This highlights the role of conducting a prospective, randomized trial in PRCC testing combination vs. single-agent therapy.
Benjamin Maughan and the team hypothesize that the combination of cabo and atezolizumab (cabo/atezo) will have higher clinical activity than single agent cabo.
Researchers designed this prospective study for a randomized phase II clinical trial being conducted through the NCTN and led by SWOG. The primary endpoint is a comparison of PFS between cabo vs. cabo/atezo. Secondary endpoints include objective response rate (ORR), overall survival (OS), and safety.
Patients are treated with cabo (60 mg/day) vs. cabo/atezo (60 mg/day + 1200 mg) q3 weeks. About 200 patients will be enrolled and randomized 1:1. Key inclusion criteria include a pathologic confirmation of PRCC, presence of metastasis, 0-1 prior systemic lines of therapy for metastatic disease, and measurable disease as defined by RECIST 1.1 criteria.
Prior treatment with adjuvant pembrolizumab is allowed if completed more than 6 months before enrollment. Key exclusion criteria include clinically significant autoimmune disease and ongoing use of strong CYP3A4 inhibitors or strong CYP3A4 inducers.
Planned correlatives include stool microbiome testing and genomic/transcriptomic analysis from blood and baseline tissue assays. Updated enrollment and site activation status will also be presented.
Prior treatment with adjuvant pembrolizumab is allowed if completed more than 6 months before enrollment. Key exclusion criteria include clinically significant autoimmune disease and ongoing use of strong CYP3A4 inhibitors or inducers. Planned correlatives include stool microbiome testing and genomic/ transcriptomic analysis from blood and baseline tissue assays. Updated enrollment and site activation status will also be presented.
The trial was sponsored by the National Cancer Institute (NCI) and additional support from NIH/NCI grant awards: U10CA180888 and U10CA180819; Genentech, Inc (a member of the Roche Group), and Exelixis Inc.
Source: https://kcrs.kidneycan.org/wp-content/uploads/2024/06/KCRS24-Abstract-Book-6.27.24.pdf
Clinical Trial: https://clinicaltrials.gov/study/NCT05411081
Maughan B, (2024). “SWOG S2200 (PAPMET2): A phase II randomized trial of cabozantinib (cabo) with or without atezolizumab (atezo) in patients with advanced papillary renal cell carcinoma (PRCC).” Presented at KCRS 2024 (Abstract 76).
