Renal Cancer ImmunotherapyWalter Stadler

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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

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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