KEY TAKEAWAYS
- A phase II clinical trial CALYPSO aimed to investigate the efficacy of combination therapy involving savolitinib, a MET inhibitor, and durvalumab, a PD-L1 inhibitor, in patients with metastatic PRC.
- The cRR is greater than 50% of the combination therapy involving savolitinib and durvalumab in patients with metastatic PRC.
- 41 subjects who underwent advanced PRC therapy were enrolled and administered at least one dose of the study intervention.
- The study did not achieve the primary endpoint of cRR greater than 50%.
- The treated population exhibited a median progression-free survival of 4.9 months, while MET-driven patients demonstrated a median progression-free survival of 12.0 months.
- The combination of savolitinib and durvalumab was associated with a significant clinical response rate in the exploratory subset of patients with MET.
Metastatic papillary renal carcinoma (PRC) is associated with unfavorable prognoses, necessitating the development of novel therapeutic interventions. A compelling justification exists for exploring the inhibition of mesenchymal-epithelial transition receptor (MET) and programmed cell death ligand-1 (PD-L1) in this particular ailment. This study investigates the efficacy of the combination therapy involving savolitinib, a MET inhibitor, and durvalumab, a PD-L1 inhibitor. The clinical trial with identifier NCT02819596 investigated the effects of durvalumab (1,500 mg administered every four weeks) and savolitinib (600 mg administered once daily) in a phase II study with a single-arm design. Patients who had not received treatment or had been treated before and had metastatic prostate cancer were enrolled.
The primary endpoint was a confirmed response rate (cRR) greater than 50%. Secondary endpoints included progression-free survival, tolerability, and overall survival. Biomarkers were investigated based on archived tissue samples to determine the MET-driven status. 41 subjects who underwent advanced PRC therapy were included in this investigation and were administered at least one dose of the study intervention.
A significant proportion of the subjects exhibited an intermediate Heng risk score (n = 26 [63%]). The calculated cRR was 29%, with a sample size 12 and a 95% confidence interval ranging from 16 to 46. As a result, the trial did not achieve the primary endpoint. The cumulative response rate (cRR) demonstrated an increase to 53% (95% confidence interval [CI], 28 to 77) among patients with MET-driven conditions (n/N = 9/27), while it was 33% (95% CI, 17 to 54) in tumors that tested positive for PD-L1 (n/N = 9/27). The treated population exhibited a median progression-free survival of 4.9 months (95% CI, 2.5 to 10.0), while MET-driven patients demonstrated a median progression-free survival of 12.0 months (95% CI, 2.9 to 19.4). The treated population exhibited a median overall survival of 14.1 months (95% CI, 7.3 to 30.7), whereas MET-driven patients demonstrated a median overall survival of 27.4 months (95% CI, 9.3 to not reached [NR]). Seventeen patients, which accounts for 41% of the total, experienced treatment-related adverse events of grade 3 or higher. One treatment-related adverse event (cerebral infarction) was observed in a patient of grade 5. The tolerability of the combination of savolitinib and durvalumab was honored to be high. It was associated with a significant clinical response rate in the exploratory subset of patients with MET-driven conditions.
Source:https://pubmed.ncbi.nlm.nih.gov/36809050/
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT02819596
Suárez C, Larkin JMG, Patel P, Valderrama BP, Rodriguez-Vida A, Glen H, Thistlethwaite F, Ralph C, Srinivasan G, Mendez-Vidal MJ, Hartmaier R, Markovets A, Prendergast A, Szabados B, Mousa K, Powles T. Phase II Study Investigating the Safety and Efficacy of Savolitinib and Durvalumab in Metastatic Papillary Renal Cancer (CALYPSO). J Clin Oncol. 2023 May 10;41(14):2493-2502. doi: 10.1200/JCO.22.01414. Epub 2023 Feb 21. PMID: 36809050.
