renal cancer immunotherapy
Post on 22-Feb-2016
82 Views
Preview:
DESCRIPTION
TRANSCRIPT
Renal Cancer ImmunotherapyWalter Stadler
2
Renal cancer natural history
Manola J et al. Clin Cancer Res 2011;17:5443-5450
International prognostic modelβ SE
Square root of days from diagnosis to study entry −0.0192 0.002
ECOG performance status 0 −1.524 0.11
ECOG performance status 1 −0.838 0.11
Number of metastatic sites 0.324 0.032
Protocol immunotherapy −0.574 0.094
Natural log of hemoglobin −2.47 0.20
Natural log of LDH 0.611 0.062Square root of white blood count 0.623 0.071
1/Square root of alkaline phosphatase −6.665 1.39
Serum calcium 0.105 0.033
Treatment: HD IL2• Cytokine Working Group trial HD IL2 vs sc IL2/IFNA
– HD IL2: 600,000 IU/kg q8o x 14 doses– sc IL2/IFNA: 5 x 106 IU/m2 4d/wk IL2; 5 x106 IU/m2 2d/wk
• Selection criteria– Non-clear cell have minimal to no benefit– Suggestion that post-VEGFR TKI treatment has higher toxicity
and lower efficacy
sc IL2/IFNA HD IL2
Pt number 91 95
Deaths 1 1
CR 3 8 (p= 0.21)
PR 6 14
Resp. Duration 15 mo 24 mo (p=0.18)
Med. Surv. 13 mo 17 mo (p = 0.21)
Durable 3 yr CR 0 7 (p=0.01)
Nivolumab (anti-PD1) in renal cancer
Population Dose(mg/kg)
Patients(n)
ORRn (%)
Duration of Response
(mo)
SD 24 wk
n (%)
PFSR at
24 wk(%)
ALL RCC 1, 10 33 9 (27) 5.6+ to 22.3+ 9 (27) 56
RCC1 17 4 (24) 5.6+ to17.5+ 4 (24) 47
10 16 5 (31)* 8.4 to 22.3+ 5 (31) 67
*One CR.
• Phase 3 vs everolimus in progress• Multiple PD1 pathway inhibitor trials in progress
6
MPDL3280A Phase 1a (anti-PDL1)
RECIST 1.1 Response Rate
(ORR)SD of 24 Weeks or
Longer 24-Week PFS
Overall population (N = 140) 21% 16% 45%
RCC* (n = 47) 13% 32% 53%
Clear cell (n = 40) 13% 35% 57%
Non-clear cell (n = 6) 17% 0 20%
* 1 patient with unknown histology. Includes sarcomatoid and papillary RCC.All patients first dosed prior to August 1, 2012; data cutoff February 1, 2013.ORR includes unconfirmed PR/CR and confirmed PR/CR.
Cho, et al, ASCO 2013
7Renal Cancer|
Peptide vaccine• IMA901 multi-peptide
– 10 different tumor-associated– Not normal tissue– In-vitro immunogenic– HLA-A*02 restricted– Pharmaceutical grade
Metastatic diseaseHLA-A*02 positiveNo prior therapyN = 330
SunitinibIMA901 + GM-CSF
1st cycle with cyclophosphamide
Overall Survival
8Renal Cancer|
Dendritic Cell Therapy: AGS-003• RNA isolated from tumor cells• Loaded on dendritic cells isolated through leukapheresis• Administered intradermal
Metastatic diseaseNo prior therapyCytoreductive nephrectomyN = 450
Sunitinib + AGS-003
Overall Survival
9Renal Cancer|
RCC Immunotherapy Conclusions• Has always been considered an “immunotherapy
responsive tumor• HD-IL2 leads to rare sustained complete responses• PD1 pathway inhibitors are promising• Other immunotherapies are being investigated
top related