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
2927 - Singapore Caregiver Quality Of Life Scale (SCQOLS): Turkish Validity and Reliability Study
Presenter: Nur Basak
Session: Poster Display session 3
Resources:
Abstract
5066 - Screening for Psicosocial Distress in recently diagnosed cancer patients
Presenter: Eva Baillès
Session: Poster Display session 3
Resources:
Abstract
6074 - Socio-demographic characteristics and quality of life analysis of cancer survivors followed at a Primary Care Center.
Presenter: Begona Grana Suarez
Session: Poster Display session 3
Resources:
Abstract
5129 - The adhesion in the screening measures in carrying patients of breast cancer and ovary hereditary and the relationship with the psychological aspects
Presenter: Melinda Concepcion
Session: Poster Display session 3
Resources:
Abstract
5635 - Assessment of emotional discomfort of oncological patients in the first nursing visit at Donostia University Hospital
Presenter: Elena Uranga
Session: Poster Display session 3
Resources:
Abstract
858 - A systematic review and meta-analysis of the distress thermometer for the screening of distress in Chinese patients with cancer
Presenter: Hui Hui Sun
Session: Poster Display session 3
Resources:
Abstract
4475 - Pharmacist and Nurse (PN) Led Melanoma Immunotherapy Clinic: Patient Experience Survey
Presenter: Dharmisha Chauhan
Session: Poster Display session 3
Resources:
Abstract
1871 - Phone Triage & Acute Review Clinics: The emerging role of the Oncology Specialist Nurse
Presenter: Fiona Barrett
Session: Poster Display session 3
Resources:
Abstract
5193 - Patient reported outcomes during immunotherapy: symptom burden in daily clinical practice
Presenter: José Koldenhof
Session: Poster Display session 3
Resources:
Abstract
2453 - Factors related to hospital length of stay, re-admissions and unplanned care for patients with cancer, an on-going study
Presenter: Helena Ullgren
Session: Poster Display session 3
Resources:
Abstract