Abstract 3515
Background
MEDI0680 is a humanised IgG4κ anti-programmed cell death-1 (PD-1) mAb. We hypothesised that simultaneous blockade of PD-1:PD-L1/PD-L2 with MEDI0680 (M) and PD-1:PD-L1/CD80 with anti-PD-L1 mAb durvalumab (D) would improve efficacy vs blockade of the PD-1:PD-L1/PD-L2 pathway (with nivolumab; N) alone. M+D was well tolerated in the dose-escalation phase of a Phase I/II study in pts with advanced solid tumours, with an ORR of 33% (10/30; including 3/4 RCC pts). In the Phase II portion of the study, we compared M+D to N in a dose-expansion cohort of pretreated, immunotherapy (IO)-naïve pts with metastatic ccRCC.
Methods
Eligible pts had received 1–3 prior therapy lines, no prior IO exposure and ≥1 measurable lesion. They were randomised 2:1 (stratified by MSKCC risk group and PD-L1 expression) to M 20 mg/kg IV + D 750 mg Q2W or N 240 mg IV Q2W until unacceptable toxicity or disease progression, for ≤2 years. Endpoints included investigator-assessed ORR by RECIST v1.1 (primary endpoint), PFS and safety (secondary). Sample size was ∼60 to detect a difference of 26.0% (ie, ORR = 47.5%, assuming ORR of 21.5% for N) with 76% power at a 1-sided significance level of 0.10.
Results
By Feb 24, 2019, 63 pts were randomised. Baseline pt/disease characteristics were generally well balanced, but more pts on N had favourable MSKCC risk (7/21; 33.3%) vs M+D (10/42; 23.8%). ORR was 14.3% (6/42; 2 CR, 4 PR; plus 2 unconfirmed PR) vs 19.0% (4/21; 4 PR, 0 unconfirmed) for M+D and N, respectively. There was no difference between arms in ORR by PD-L1 expression (<1% vs ≥ 1%). All responses are ongoing. Median PFS was 3.6 months in both arms. Grade 3/4 treatment-related AEs (TRAEs) occurred in 26% on M+D (including 1 case of autoimmune encephalitis) and 19% on N. On M+D, 12% had TRAEs leading to treatment discontinuation, including colitis or diarrhoea (n = 3) and increased ALT/transaminases (n = 2), vs 5% on N (pancreatitis and increased lipase and amylase in 1 pt). There were no Grade 5 TRAEs.
Conclusions
Efficacy was similar with combined M+D and N monotherapy in pts with TKI-pretreated, IO-naïve, metastatic ccRCC, but more pts discontinued M+D due to TRAEs.
Clinical trial identification
NCT02118337.
Editorial acknowledgement
Aaron Korpal, PhD, of Cirrus Communications (Macclesfield, UK), an Ashfield company, funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
M.H. Voss: Research grant / Funding (institution): BMS; Research grant / Funding (institution): Genentech; Honoraria (self): Eisai; Honoraria (self): Exelixis; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Calithera; Honoraria (self): Corvus. A.A. Azad: Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Non-remunerated activity/ies: Astellas; Honoraria (self), Advisory / Consultancy: Novartis; Research grant / Funding (institution), Non-remunerated activity/ies: Merck Serono; Honoraria (self), Advisory / Consultancy: Tolmar; Honoraria (self), Advisory / Consultancy, Non-remunerated activity/ies: Amgen; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self): Bayer; Honoraria (self), Advisory / Consultancy: Telix Pharmaceuticals; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Sanofi. A.R. Hansen: Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): GSK; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Boston Biomedical; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca. J.E. Gray: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Genentech; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Triptych Health Partners; Research grant / Funding (institution): Array; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Epic Sciences; Research grant / Funding (institution): BMS; Research grant / Funding (institution): BI; Research grant / Funding (institution): Trovagene; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): Blueprint; Research grant / Funding (institution): Novartis. I. Achour: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. H. Hu: Full / Part-time employment: AstraZeneca. L. Lewis: Travel / Accommodation / Expenses, Full / Part-time employment: AstraZeneca. F.L. Walcott: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. S.F. Oosting: Research grant / Funding (institution): Celldex; Research grant / Funding (institution): Novartis. All other authors have declared no conflicts of interest.
Resources from the same session
2344 - Lung Cancer in Europe: strengthening policy responses to address unmet needs
Presenter: Mary Bussell
Session: Poster Display session 3
Resources:
Abstract
1359 - Curative treatment timelines for breast, colorectal, lung and prostate cancer: Implications for medical leave coverage
Presenter: Selina Wong
Session: Poster Display session 3
Resources:
Abstract
4433 - Acute Diagnostic Oncology Clinic: A Unique Primary Care-Oncology Service
Presenter: Abhijit Gill
Session: Poster Display session 3
Resources:
Abstract
3506 - THE NEW MUTATIONAL MODEL IN ONCOLOGY. What changes in welfare, clinical practice, research, and regulatory procedures
Presenter: Nicola Normanno
Session: Poster Display session 3
Resources:
Abstract
3350 - Selection of a set of quality indicators (QI) for oncological clinical pathway
Presenter: Aude Fourcade
Session: Poster Display session 3
Resources:
Abstract
4400 - Sustainable drug prices at market launch: policy proposals and their empirical evidence
Presenter: Nora Fanzen
Session: Poster Display session 3
Resources:
Abstract
4118 - Impact of financial considerations on French physicians’ prescription choices for advanced non-small cell lung cancer (NSCLC)
Presenter: Nathalie Olympios
Session: Poster Display session 3
Resources:
Abstract
1340 - The direct medical cost of breast cancer in a Belgian hospital
Presenter: Hannan Lemhouer
Session: Poster Display session 3
Resources:
Abstract
1863 - Does the healthcare system approaches cancer patients for using private services during diagnostic process?
Presenter: Karolina Osowiecka
Session: Poster Display session 3
Resources:
Abstract
2637 - Measuring financial toxicity of cancer in the Italian health care system: initial results of the patient reported outcome for Fighting Financial Toxicity of cancer project (proFFiT).
Presenter: Silvia Riva
Session: Poster Display session 3
Resources:
Abstract