A randomized phase II study with ilixadencel, a cell-based immune - - PowerPoint PPT Presentation

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A randomized phase II study with ilixadencel, a cell-based immune - - PowerPoint PPT Presentation

A randomized phase II study with ilixadencel, a cell-based immune primer, plus sunitinib versus sunitinib alone in synchronous metastatic renal cell carcinoma Magnus Lindskog, MD, PhD; Uppsala University Hospital, Sweden Co-investigators: Anna


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A randomized phase II study with ilixadencel, a cell-based immune primer, plus sunitinib versus sunitinib alone in synchronous metastatic renal cell carcinoma

Magnus Lindskog, MD, PhD; Uppsala University Hospital, Sweden

Co-investigators: Anna Laurell, MD, Anders Kjellman, MD, Bohuslav Melichar, MD, Jacek Niezabitowski, MD, Pablo Maroto, MD, Henryk Zielinski, MD, Felipe Villacampa, MD, Pierre Bigot, MD, Bajory Zoltan, MD, Omi Parikh, MD, David Vazquez Alba, MD, Åsa Jellvert, MD, Tibor Flasko, MD, Enrique Gallardo Diaz, MD, Maria José Ribal Caparros, MD, Gunta Purkalne, MD, Peter Suenaert, MD, Alex Karlsson-Parra, MD, Börje Ljungberg, MD

  • M. Lindskog
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Disclaimer

  • Consulting or Advisory role

Pfizer Bristol-Myers Squibb

  • Honoraria

Pfizer Bristol-Myers Squibb Ipsen

  • M. Lindskog
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Ilixadencel: donor-derived inflammatory DCs

healthy donor leukapheresis TLR3 ligand TLR7/8 ligand IFN-γ allogeneic inflammatory DCs: ilixadencel intratumoral administration in primary tumor

  • r metastasis

ultrasound

  • r CT guided

ilixadencel chemokines: CCL3-5, CXCL9-10 cytokines: IL-12, TNF-⍺, IL-1β

  • IFN-γ production
  • tumor cell killing
  • cross-presentation
  • f tumor antigens

to CD8+ T cells patient NK cells patient bystander DCs recruitment and activation in injected tumor tissue cryopreserved up to 4 years vials

  • M. Lindskog

GM-CSF IL-4

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Phase II MERECA study: design and timelines

  • Randomized exploratory phase II study
  • Synchronous metastatic RCC in 1st line, stratified for IMDC (Heng) poor-intermediate risk
  • 8 European countries and United States; FPI April 2015, LPLV June 2019

< 8 weeks

nephrectomy n=56 n=30 ilixadencel

2 weeks

control – no injections

6 weeks

sunitinib sunitinib

X

Baseline imaging 18-month Overall Survival survival follow-up tumor response scans n=25 n=45 2:1 randomization

  • M. Lindskog
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Phase II MERECA study: endpoints

Primary:

  • OS from randomization overall and by risk group
  • 18-month survival

Secondary:

  • Safety
  • PFS from start of sunitinib
  • Proportion of Objective Response Rate (ORR) from start of sunitinib treatment

and duration of response in each subgroup

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Phase II MERECA study: patient characteristics

Ilixadencel-sunitinib Sunitinib Age median (range) 62 (41-76) 64 (49-86) Male sex no. (%) 45 (78%) 21 (70%) IMDC intermediate risk no. (%) 41 (71%) 22 (73%) IMDC poor risk no. (%) 17 (29%) 8 (27%) Sarcomatoid features no. (%) 13 (22%) 7 (23%) Sweden 19 (32.8%) 12 (40.0%) Rest of Europe 38 (65.5%) 17 (56.6%) USA 1 (1.7%) 1 (3.3%)

  • M. Lindskog
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Overall Survival by Kaplan-Meier probability curve

  • 18-months OS rate similar
  • 63% for ilixadencel-sunitinib
  • 66% for sunitinib
  • Median OS not mature
  • Progression-Free Survival

11.8 mo. ilixadencel-sunitinib 11.1 mo. for sunitinib

  • Patients alive/censored

54% (n=30) ilixadencel-sunitinib 37% (n=11) sunitinib

  • M. Lindskog

2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 0.0 0.2 0.4 0.6 0.8 1.0

Survival Probability

2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 0.0 0.2 0.4 0.6 0.8 1.0

Survival Probability

CR: Dead CR: Censored

ilixadencel-sunitinib sunitinib

  • and o

Censored patients in follow-up who were alive at last contact

2: 1:

ilixadencel-sunitinib sunitinib

56 53 48 43 42 38 36 36 34 34 33 33 29 25 24 21 19 16 12 9 6 4 4 3 3 1 1 30 28 26 23 20 20 19 19 19 19 19 17 13 10 10 9 7 4 4 4 3 1 1

1 2

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2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52

Time (Months)

0.0 0.2 0.4 0.6 0.8 1.0

Survival Probability

2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52

Time (Months)

0.0 0.2 0.4 0.6 0.8 1.0

Survival Probability

CR: Dead CR: Censored 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52

Time (Months)

0.0 0.2 0.4 0.6 0.8 1.0

Survival Probability

2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52

Time (Months)

0.0 0.2 0.4 0.6 0.8 1.0

Survival Probability

CR: Censored

16 14 13 12 11 8 6 6 5 5 5 5 4 4 4 4 4 3 2 2 1 1 1 8 7 6 5 4 4 3 3 3 3 3 2 2 1 1 1

1 2

40 39 35 31 31 30 30 30 29 29 28 28 25 21 20 17 15 13 10 7 5 3 3 3 3 1 1 22 21 20 18 16 16 16 16 16 16 16 15 11 9 9 8 7 4 4 4 3 1 1

1 2

ilixadencel-sunitinib sunitinib

Median OS

  • 10.6 mo. for ilixadencel-sunitinib
  • 9.3 mo. for sunitinib

Median OS not mature

2: 1:

ilixadencel-sunitinib sunitinib

2: 1:

ilixadencel-sunitinib sunitinib

IMDC Intermediate risk IMDC Poor risk

ilixadencel-sunitinib sunitinib

  • M. Lindskog

Overall Survival by risk group

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Ilixadencel-sunitinib Sunitinib

ORR (Best Overall Response) 44% (n=20/45) 48% (n=12/25)

  • Complete Response

11%* (n=5/45) 4.0% (n=1/25)

  • Partial Response

33% (n=15/45) 44% (n=11/25)

Confirmed ORR 42% (n=19/45) 24% (n=6/25)

  • Complete Response

6.7% (n=3/45) 0% (n=0/25)

  • Partial Response

36% (n=16/45) 24% (n=6/25)

  • Median duration of response was 7.1 mo (ilixadencel-sunitinib) vs 2.9 mo (sunitinib)
  • Sarcomatoid features were not associated with ORR to ilixadencel-sunitib

* Two patients had CR as best response at last available CT scan (at 10 mo. and 18 mo. respectively)

Tumor response (according to RECIST 1.1 by independent blinded review)

  • M. Lindskog
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Phase II MERECA study: safety and tolerability

  • Safety profile of combination treatment similar to sunitinib alone
  • Most common ilixadencel-related AE was pyrexia
  • No signs of induced autoimmunity; 57% (n=32) of patients treated with ilixadencel developed de

novo ilixadencel-specific alloantibodies

All, Grade 3+ and Serious Adverse Events Treatment-related Adverse Events

  • M. Lindskog
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Phase II MERECA study: Conclusions

  • Feasibility and safety of ilixadencel-sunitinib in synchronously metastatic RCC confirmed
  • No difference in 18 mo. OS or in PFS
  • OS data immature – follow-up ongoing
  • Late separation of survival curves may indicate OS signal and warrants further follow-up
  • Higher rate of confirmed PR and CR in ilixadencel-sunitinib arm vs. sunitinib alone
  • All 5 CR in ilixadencel arm were alive after a minimal FU of 33 months
  • M. Lindskog
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Acknowledgements

  • The patients and their families
  • Co-investigators and research nurses

Sponsor

Immunicum AB (publ)

  • M. Lindskog