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
5389 - Two-weekly accelerated BEP (aBEP) regimen as induction chemotherapy (CT) in intermediate and poor prognosis patients (pts) with nonseminomatous germ cell tumors (NSGCT): final results of phase II trial.
Presenter: Alexey Tryakin
Session: Poster Display session 3
Resources:
Abstract
2934 - Differential expression of circulating miR375 and miR371 to detect teratoma and viable germ cell malignancy
Presenter: Lucia Nappi
Session: Poster Display session 3
Resources:
Abstract
3585 - Prognosis of anaemia in disseminated testicular germ cell tumours. On behalf of the Spanish Germ Cell Cancer Group (SGCCG)
Presenter: Esmeralda Garcia Torralba
Session: Poster Display session 3
Resources:
Abstract
2254 - The Effects Of Primary Testicular Tumor Localization On Prognosis In Patients With Nonseminomatous Testis Cancer
Presenter: Birol Yildiz
Session: Poster Display session 3
Resources:
Abstract
4505 - Initial Results of a Phase II study of Nivolumab and Ipilimumab in Metastatic Adrenal Tumors.
Presenter: Matthew Campbell
Session: Poster Display session 3
Resources:
Abstract
3369 - NEMIO: a randomized phase II trial evaluating efficacy and safety of dose dense MVAC (ddMVAC) + durvalumab +/- tremelimumab as neoadjuvant treatment in patients with bladder muscle-invasive urothelial carcinoma
Presenter: Constance Thibault
Session: Poster Display session 3
Resources:
Abstract
2075 - KEYNOTE-866: Phase 3 Study of Perioperative Pembrolizumab (pembro) or Placebo (pbo) in Combination With Neoadjuvant Chemotherapy in Cisplatin (cis)-Eligible Patients (pts) With Muscle-Invasive Bladder Cancer (MIBC)
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract
4824 - KEYNOTE-905: A Phase 3 Study of Cystectomy Plus Perioperative Pembrolizumab Versus Cystectomy Alone in Cisplatin (cis)-Ineligible Patients (pts) With Muscle-Invasive Bladder Cancer (MIBC)
Presenter: Matthew Galsky
Session: Poster Display session 3
Resources:
Abstract
2253 - Phase 3 LEAP-011 trial: First-Line Pembrolizumab With Lenvatinib in Patients With Advanced Urothelial Carcinoma Ineligible to Receive Platinum-Based Chemotherapy
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
4310 - PULSE : A Single Arm Trial Assessing The Activity and Safety of Avelumab Immunotherapy Maintenance among Patients With Locally Advanced or Metastatic Squamous Cell Penile Carcinoma (mSCPC).
Presenter: Noemie Gassian
Session: Poster Display session 3
Resources:
Abstract