Trial Data Show Savolitinib Does Not Improve Outcomes for Patients with RCC

Results from the phase 2 clinical trial CALYPSO (NCT02819596) showed that the addition of savolitinib in treatment of patients with previously treated advanced clear-cell renal cell carcinoma (ccRCC) did not improve patient outcomes. The final data from this trial was presented at the 2025 European Society for Medical Oncology (ESMO) Congress on October 17, 2025 in Berlin, Germany by Laurence Albiges, MD, PhD, Institute Gustave Roussy Department of Medical Oncology, Villejuif, France.¹

CALYPSO is a phase 2 trial evaluating the safety and efficacy of durvalumab (D; Imfinzi), savolitinib (S), and tremelimumab (T; Imjudo) in patients with previously treated advanced RCC.² The randomized study examined patients who had been previously treated with VEGF-targeted therapy but were naive to immune checkpoint and MET inhibitors.

Patients were randomized 1:1:1 to receive durvalumab (n = 39), durvalumab + tremelimumab (n = 39), or durvalumab + savolitinib (n = 39). The primary end point of overall response rate (ORR) with a threshold of ≥ 50% for further evaluation was not achieved. The ORRs for each arm were 10% (D), 28% (D+T), and 13% (D+S). The median duration of response (DOR) per arm was 9.8 months (D), 19.4 months (D+T), and 13.3 months (D+S). The 12-month progression-free survival (PFS) rates were 28% (D) (95% CI, 15%–42%), 33% (D+T) (95% CI, 19%–48%), and 20% (D+S) (95% CI, 9%–34%). Median overall survival (OS) for each arm was 25.8 months (D), 24.2 months (D+T), and 16.3 months (D+S). The minimum follow-up was 3 years.¹

In a comparison of D vs D+T and D vs D+S, there were HRs of 0.864 (80% CI, 0.607–1.229) and 1.549 (80% CI, 1.108–2.165), respectively.¹

In the MET-driven subgroup (n=17), OS HR for S (S+DS) vs non-S (D+DT) was 0.342 (80% CI; 0.154–0.761). The median tumor mutational burden (TMB) was 2.5 mutations/Mb (n=62) with no clear association with outcomes.¹

Albigies made a point to differentiate the CALYPSO study from similar studies, saying “Given the IO-naive profile, this study has to be put in a different box as other studies that were PD-1–refractory.”¹

Patient inclusion criteria included but were not limited to having ccRCC, having measurable or advanced disease, receiving previous VEGF targeted therapy, having an ECOG score of 0-1, and having no contraindications for immune or MET therapy.

Patient exclusion criteria included but were not limited to: participation in another clinical study with an investigational product 28 days before enrollment, any previous treatment with PD-1 or anti–PD-L1 therapeutic antibody, having a significant cardiovascular disease, and currently receiving treatment with therapeutic doses of warfarin sodium.

Albiges explained during her presentation that, “We see a differential response rate between the different arms but we don’t see any benefit in terms of PFS and OS.”¹

Albigies concluded the presentation by noting the unlikelihood of a randomized phase 3 trial and urging physicians to expose patients to a PD-1 inhibitor.

DISCLOSURES: Albiges disclosed having a consulting or advisory role with Amgen, AstraZeneca, Astellas Pharma, Bristol-Myers Squibb, Daiichi, Eisai, Ipsen, Janssen, Merck, MSD, Novartis, Pfizer, Roche, Telix, and Xencor.

REFERENCES:

1. Albiges L. Mini oral session 1 – GU tumors: Renal. Discussion: Can we combine more in LI and L2? Final efficacy data and biomarker analysis from the clear cell cohort of CALYPSO. Presented at the European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract 2605MO.

2. MEDI4736 Combinations in Metastatic Renal Cell Carcinoma (CALYPSO). ClinicalTrials.gov. Updated November 4, 2024. Accessed October 22, 2025. https://clinicaltrials.gov/study/NCT02819596