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 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 Slides are the property M. Lindskog #ImmunoOnc20 PRESENTED AT: of the author, permission PRESENTED BY: required for reuse.

Disclaimer • Consulting or Advisory role Pfizer Bristol-Myers Squibb • Honoraria Pfizer Bristol-Myers Squibb Ipsen Slides are the property M. Lindskog #ImmunoOnc20 PRESENTED AT: of the author, permission PRESENTED BY: required for reuse.

Ilixadencel: donor-derived inflammatory DCs healthy donor cryopreserved ilixadencel leukapheresis up to 4 years chemokines : CCL3-5, CXCL9-10 cytokines : IL-12, TNF- ⍺ , IL-1β TLR3 ligand GM-CSF TLR7/8 ligand IL-4 recruitment and activation IFN-γ in injected tumor tissue patient NK cells patient bystander DCs intratumoral administration in primary tumor vials or metastasis allogeneic -IFN-γ production -cross-presentation ultrasound -tumor cell killing of tumor antigens inflammatory DCs: or CT guided to CD8+ T cells ilixadencel Slides are the property M. Lindskog #ImmunoOnc20 PRESENTED AT: of the author, permission PRESENTED BY: required for reuse.

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 nephrectomy Baseline 18-month imaging Overall Survival X n=30 n=25 control – no injections sunitinib survival < 8 weeks 6 weeks 2:1 randomization follow-up n=56 n=45 ilixadencel sunitinib 2 weeks tumor response scans Slides are the property M. Lindskog #ImmunoOnc20 PRESENTED AT: of the author, permission PRESENTED BY: required for reuse.

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 Slides are the property #ImmunoOnc20 PRESENTED AT: of the author, permission PRESENTED BY: required for reuse.

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%) Slides are the property M. Lindskog #ImmunoOnc20 PRESENTED AT: of the author, permission PRESENTED BY: required for reuse.

Overall Survival by Kaplan-Meier probability curve • 18-months OS rate similar 1.0 1.0 • 63% for ilixadencel-sunitinib • 66% for sunitinib 1: ilixadencel-sunitinib 0.8 0.8 sunitinib 2: Survival Probability Survival Probability • Median OS not mature 0.6 0.6 • Progression-Free Survival 0.4 0.4 11.8 mo. ilixadencel-sunitinib 11.1 mo. for sunitinib 0.2 0.2 • Patients alive/censored CR: Censored CR: Dead 0.0 0.0 54% (n=30) ilixadencel-sunitinib 37% (n=11) sunitinib 0 0 2 2 4 4 6 6 8 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 1 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 ilixadencel-sunitinib o and o Censored patients in follow-up 2 sunitinib 30 28 26 23 20 20 19 19 19 19 19 17 13 10 10 9 7 4 4 4 3 1 1 0 who were alive at last contact Slides are the property M. Lindskog #ImmunoOnc20 PRESENTED AT: of the author, permission PRESENTED BY: required for reuse.

Overall Survival by risk group IMDC Intermediate risk IMDC Poor risk 1.0 1.0 1.0 1.0 Median OS not mature Median OS • 10.6 mo. for ilixadencel-sunitinib 0.8 0.8 0.8 0.8 Survival Probability Survival Probability Survival Probability Survival Probability • 9.3 mo. for sunitinib 0.6 0.6 0.6 0.6 0.4 0.4 0.4 0.4 0.2 0.2 0.2 0.2 1: 1: ilixadencel-sunitinib ilixadencel-sunitinib CR: Censored sunitinib 2: sunitinib 2: CR: Dead CR: Censored 0.0 0.0 0.0 0.0 0 0 2 2 4 4 6 6 8 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 0 0 2 2 4 4 6 6 8 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 1 1 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 16 14 13 12 11 8 6 6 5 5 5 5 4 4 4 4 4 3 2 2 1 1 1 0 ilixadencel-sunitinib Time (Months) Time (Months) ilixadencel-sunitinib Time (Months) Time (Months) 2 2 22 21 20 18 16 16 16 16 16 16 16 15 11 9 9 8 7 4 4 4 3 1 1 0 8 7 6 5 4 4 3 3 3 3 3 2 2 1 1 1 0 sunitinib sunitinib Slides are the property M. Lindskog #ImmunoOnc20 PRESENTED AT: of the author, permission PRESENTED BY: required for reuse.

Tumor response (according to RECIST 1.1 by independent blinded review) Ilixadencel-sunitinib Sunitinib 44% (n=20/45) 48% (n=12/25) ORR (Best Overall Response) - 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) * Two patients had CR as best response at last available CT scan (at 10 mo. and 18 mo. respectively) • 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 Slides are the property M. Lindskog #ImmunoOnc20 PRESENTED AT: of the author, permission PRESENTED BY: required for reuse.

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 Slides are the property M. Lindskog #ImmunoOnc20 PRESENTED AT: of the author, permission PRESENTED BY: required for reuse.

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 Slides are the property M. Lindskog #ImmunoOnc20 PRESENTED AT: of the author, permission PRESENTED BY: required for reuse.

Acknowledgements • The patients and their families • Co-investigators and research nurses Sponsor Immunicum AB (publ) Slides are the property M. Lindskog #ImmunoOnc20 PRESENTED AT: of the author, permission PRESENTED BY: required for reuse.