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Published on: April 22, 2019
A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with
Martin H Voss1, Arun A Azad2, Aaron R Hansen3
1Memorial Sloan Kettering Cancer Center, New York, New York.
Purpose:
MEDI0680 is a humanized anti-programmed cell death-1 (PD-1) antibody, and durvalumab is an anti-PD-L1 antibody. Combining treatment using these antibodies may improve efficacy versus blockade of PD-1 alone. This phase II study evaluated antitumor activity and safety of MEDI0680 plus durvalumab versus nivolumab monotherapy in immunotherapy-naïve patients with advanced clear-cell renal cell carcinoma who received at least one prior line of antiangiogenic therapy.
Patients And Methods:
Patients received either MEDI0680 (20 mg/kg) with durvalumab (750 mg) or nivolumab (240 mg), all intravenous, every 2 weeks. The primary endpoint was investigator-assessed objective response rate (ORR). Secondary endpoints included best overall response, progression-free survival (PFS), safety, overall survival (OS), and immunogenicity. Exploratory endpoints included changes in circulating tumor DNA (ctDNA), baseline tumor mutational burden, and tumor-infiltrated immune cell profiles.
Results:
Sixty-three patients were randomized (combination, n = 42; nivolumab, n = 21). ORR was 16.7% [7/42; 95% confidence interval (CI), 7.0-31.4] with combination treatment and 23.8% (5/21; 95% CI, 8.2-47.2) with nivolumab. Median PFS was 3.6 months in both arms; median OS was not reached in either arm. Because of adverse events, 23.8% of patients discontinued MEDI0680 and durvalumab and 14.3% of patients discontinued nivolumab. In the combination arm, reduction in ctDNA fraction was associated with longer PFS. ctDNA mutational analysis did not demonstrate an association with response in either arm. Tumor-infiltrated immune profiles showed an association between immune cell activation and response in the combination arm.
Conclusions:
MEDI0680 combined with durvalumab was safe and tolerable; however, it did not improve efficacy versus nivolumab monotherapy.
Insights
Combining MEDI0680 with durvalumab did not improve outcomes compared to nivolumab monotherapy in advanced clear-cell renal cell carcinoma patients. This combination therapy was safe but did not show superior efficacy in this immunotherapy-naïve population.
Area of Science:
- Immunotherapy
- Oncology
- Renal Cell Carcinoma Research
Background:
- The combination of anti-programmed cell death-1 (PD-1) and anti-PD-L1 antibodies may offer improved efficacy over PD-1 blockade alone.
- MEDI0680 is a humanized anti-PD-1 antibody, and durvalumab is an anti-PD-L1 antibody.
Purpose of the Study:
- To evaluate the antitumor activity and safety of MEDI0680 plus durvalumab compared to nivolumab monotherapy.
- The study focused on immunotherapy-naïve patients with advanced clear-cell renal cell carcinoma (ccRCC) who had previously received antiangiogenic therapy.
Main Methods:
- A phase II study randomized 63 patients to receive either MEDI0680 plus durvalumab or nivolumab monotherapy intravenously every two weeks.
- Primary endpoint was investigator-assessed objective response rate (ORR); secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.
- Exploratory endpoints analyzed circulating tumor DNA (ctDNA) and tumor-infiltrated immune cell profiles.
Main Results:
- The objective response rate (ORR) was 16.7% for the combination arm and 23.8% for the nivolumab arm.
- Median progression-free survival (PFS) was 3.6 months in both treatment groups.
- While the combination was safe, adverse events led to discontinuation in 23.8% of patients in the combination arm versus 14.3% in the nivolumab arm. Reduction in ctDNA fraction correlated with longer PFS in the combination arm.
Conclusions:
- MEDI0680 combined with durvalumab demonstrated acceptable safety and tolerability.
- The combination therapy did not show improved efficacy compared to nivolumab monotherapy in this patient population.
- Exploratory analyses suggested potential associations between immune cell activation and response in the combination arm.
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