The combination of MEDI0680 and durvalumab was well-tolerated and safe but did not show any significant improvement in effectiveness compared to nivolumab monotherapy, in this study.
Renal cell carcinoma (RCC) accounts for 2–3% of all adult malignancies. Advanced or metastatic RCC has a poor prognosis, and standard-of-care treatment options are limited. Immunotherapy has emerged as a promising treatment strategy, and several immunotherapy agents have been approved for the treatment of advanced RCC. A clinical trial was conducted to compare the efficacy and safety of MEDI0680 plus durvalumab versus nivolumab for advanced RCC. The findings of the trial were published in the journal Clinical Cancer Research.
Patient Demographics and Clinical Characteristics
A total of 63 patients were enrolled in the study, with 42 patients receiving MEDI0680 plus durvalumab and 21 patients receiving nivolumab. Patient demographics and baseline disease characteristics were generally well-balanced between study arms, with some exceptions.
Comparison of MEDI0680 Plus Durvalumab and Nivolumab Monotherapy Response Rates
The primary endpoint was investigator-assessed objective response rate (ORR), for which values of 16.7% with MEDI0680 plus durvalumab and 23.8% with nivolumab were obtained. In the two treatment arms, the difference was insignificant. Complete response was observed in 4.8% of patients in the combination arm. No patients in the nivolumab arm had a complete response. The disease control rate at 24 weeks was 38.1% in both treatment arms. No significant difference in ORR based on programmed death receptor ligand-1 status between treatment arms.
Change in Tumor Burden and Progression-Free Survival
Progression-free survival (PFS) was comparable between the combination and nivolumab arms. Patients in both treatment arms had a median PFS of 3.6 months, with no significant difference between the MEDI0680 plus durvalumab arm and the nivolumab arm. Median overall survival (OS) was not reached in either arm, and OS rates at 12 months were 75.2% in the MEDI0680 and durvalumab arm and 83.6% in the nivolumab arm.
Incidence of Treatment-Related Adverse Events
Treatment-related adverse events (TRAE) of any grade occurred in 92.9% of patients treated with the combination and 81.0% treated with nivolumab. TRAEs of grade 3–4 severity were observed in both treatment arms. In total, 23.8% of patients in the combination arm discontinued MEDI0680 plus durvalumab due to an AE, and 14.3% of patients in the nivolumab arm discontinued nivolumab due to an AE.
Anti-Drug Antibody Response to MEDI0680 and Durvalumab in Patients
The study analyzed anti-drug antibody levels in patients before and after treatment with MEDI0680 and durvalumab. Of the 40 patients treated with MEDI0680, 10% showed a positive response at baseline, and 5.1% showed a positive response post-treatment. For durvalumab, one patient had a positive response at baseline, and two patients showed a positive response post-treatment, with two patients having persistent positive responses.
Translational Biomarker Analysis
The change in circulating tumor DNA (ctDNA) was measured by percent change from baseline in mean variant allele frequency. ctDNA reductions were observed in several patients, with complete and partial responses in both treatment groups. No association was observed between baseline blood tumor mutational burden (bTMB) score and response.
Voss, M. H., Azad, A. A., Hansen, A. R., Gray, J. E., Welsh, S. J., Song, X., Kuziora, M., Meinecke, L., Blando, J., Achour, I., Wang, Y., Walcott, F. L., & Oosting, S. F. (2022). A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. Clinical Cancer Research, 28(14), 3032-3041. https://doi.org/10.1158/1078-0432.Ccr-21-4115