(UroToday.com) The 2025 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Annual Symposium held in San Francisco, CA between February 13–15, 2025 was host to a renal cell cancer rapid oral abstract session. Dr. Frankie Jackson-Spence presented the final overall survival and new ctDNA analysis from CALYPSO in MET-driven advanced papillary renal cancer.
Metastatic papillary renal cancer has poor outcomes, and new treatments are needed. There is a strong rationale for investigating the combination of mesenchymal epithelial transition receptor (MET) and programmed cell death ligand-1 (PD-L1) inhibitors in this disease.
CALYPSO is a phase II study investigating savolitinib (600 mg once daily) + durvalumab (1,500 mg every four weeks) in advanced papillary RCC patients. Treatment-naïve or previously treated patients with metastatic papillary RCC were included. Initial results of this trial were published in The Journal of Clinical Oncology in 2023. Forty-one patients were enrolled in this study and received at least one dose of study treatment. The confirmed response rate was 29%, with the trial failing to meet its pre-defined response rate of >50%. The confirmed response rate increased to 53% in MET-driven patients and was 33% in PD-L1-positive tumors. The median progression-free survival (PFS) was 5 months in the treated population and 12 months in the MET-driven patients. The corresponding median overall survivals were 14.1 and 27.4 months, respectively.1
In this updated final survival analysis, the median PFS and OS in the intent to treat population were 6.5 months and 18.3 months, respectively.
In the MET-driven population, the median PFS was 13.9 months, and the median OS was 27.4 months. The hazard ratios (HR) for PFS and OS in MET-driven, versus non-MET-driven, were 0.36 (p=0.02) and 0.76 (p=0.43), respectively.
The median duration of response was 11.3 months.
66% of patients were PD-L1+, and 32% were both MET-driven/PD-L1+. The PD-L1 biomarker did not enrich for responders. 27% patients had tissue TMB >median (2.52 mut/Mb). TMB was also not associated with survival outcomes.
For ctDNA analysis, FoundationOne®CDx analysis (CGP) was performed on tissue samples of papillary RCC patients enrolled on the CALYPSO trial (n=32). FoundationOne®Tracker was used for cDNA analysis and was positive for 21 patients.
Of the 21 patients with available ctDNA results at baseline, 10 (48%) were ctDNA positive, which was associated with a shorter median OS of 7.3 vs 33.3 months (HR: 2.73, 95% CI: 0.88–8.47).
Two patients achieved a ctDNA clearance (i.e., positive-negative) at during weeks 4–16 (ORR: partial response for both). These patients had superior overall survival rates (median: 31.3 versus 7.2 months), compared to those with no ctDNA clearance.
The results of this trial provide the foundation for SAMETA, an open-label, three-arm, multicenter, phase IlI study of savolitinib + durvalumab versus sunitinib and durvalumab monotherapy in patients with MET-driven, unresectable, locally advanced/metastatic papillary renal cell carcinoma:
Dr. Jackson-Spence concluded as follows:
- This phase II study shows savolitinib + durvalumab combination has activity in papillary renal cancer
- Tumour responses are enriched in the MET-driven group with median OS of 27.4 months
- Responses were observed irrespective of PD-L1 status and TMB status
- 48% were cDNA positive at baseline
- ctDNA status at baseline has prognostic value
- Few patients had trackable MET alterations
- The promising efficacy and safety profile for savolitinib in combination with durvalumab in MET-driven papillary RCC is being further investigated in the SAMETA trial (NCT05043090).
Presented by: Frankie Jackson-Spence, MBChB, BMedSc, PCGAP, Clinical Research Fellow, Barts Cancer Institute, Queen Mary University London, London, UK
Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.
Related content: CALYPSO Trial: Savolitinib and Durvalumab in Advanced Papillary Renal Cancer - Francesca Jackson-Spence