ASCO Annual Meeting 2017 Bart Neyns MD PhD, UZ Brussel. 20th Post-ASCO Meeting, 24th June 2016

Transcription

1 ASCO Annual Meeting 2017 Bart Neyns MD PhD, UZ Brussel 20th Post-ASCO Meeting, 24th June 2016

2 FAS-L Cancer Testis Ag Differentiation Ag Neo-antigens PD-1 CTL CD8+ Tcell CTLA-4 CD28 B7.1/B7.2 Cancer PD-L1 PD-1 CTL CD8+ Tcell T h 1 CD4+ Tcell TCR MHC I Mature mydc M2 Macrophage & MDSC CD4+ Treg CTLA-4 T h 2 CD4+ Tcell Ansell SM, et al. N Engl J Med : Barrett MT, et al. Oncotarget. 2015;6: Zelanay S, et al. Cell. 2015;162 Zou W. et al Science of translational medicine ; Spranger Oncoimmunology 2016; Broz et al Cancer Cell 2014; Roberts Cancer Cell 2016

3 T-Cell Inflammed Tumor Microenvironment Hot Tumor Non T-Cell Inflammed Tumor Microenvironment Cold Tumor T-Cell Excluded T-Cell Neglected

4 T-Cell Inflammed Tumor Microenvironment Hot Tumor

5 ASCO AM 2017 CANCER CELL T-Cell Inflammed Tumor Microenvironment Hot Tumor Anti-PD-1 mab PD-L1 PD-1 T-Cell Gatekeeper Single Molecular Interaction 3y OS 1st line apd1 PEMBRO advanced melanoma & outcome after treatment discontinuation in responders apd1/actla-4 for melanoma brain metastases Ipilimumab dosing in the adjuvant setting apd1 in cuscc, Avelumab in mmcc

6 35% BRAF/MEK pretreated 2017 ASCO Annual Meeting: Survival update with a median Follow-Up of 33.9 Months

7 Kaplan-Meier Estimates of Survival in Total Population (Median Follow-Up, 33.9 Mo) Overall Survival Progression-Free Survival per irrc by Investigator Arm Events, n HR (95% CI) Pembrolizumab ( ) Median, mo (95% CI) 32.3 (24.5-NR) 33-mo rate, % 50% Arm Events, n HR (95% CI) Pembrolizumab ( ) Median, mo (95% CI) 8.3 ( ) 33-mo rate, % 31% Ipilimumab ( ) 39% Ipilimumab ( ) 14% Analysis includes all randomized patients with measurable disease at baseline who received 1 pembrolizumab dose. Data cutoff date: Nov 3, 2016.

8 Long-term survivors

9 Disposition of Patients Who Completed Protocol- Specified 2y on PEMBRO (Median Follow-Up 9 Mo after stopping PEMBRO) PFS (irrc, Investigator) From Last PEMBRO Dose to PD or Death in Patients Who Completed Protocol-Specified 2y on PEMBRO (n = 104) 91% of patients who discontinued pembrolizumab following the protocol-specified 2 years of treatment continue to be progression-free after a median follow-up of nearly 10 months

10 509 pts with advanced melanoma treated with PEMBRO outside of an interventional clinical trial at 9 European hospitals 40 pts (8%) PEMBRO ongoing 343 pts (67%) 108 pts (21%) stopped in absence of PD 81 (16%) Pt/MD decision 29 (6%)@AE PFS from last dose to PD: AE vs Pt/MD decision PFS from last dose to PD: according to BORR Adverse event Patient/physician choice Time, weeks Time, weeks Yanina Jansen

11 KEYNOTE-006 Robert C et al ASCO AM Real-life data Jansen Y et al ASCO AM

12 Melanoma Brain Metastases 1 out of 3 diagnoses of all brain metastases 1 Clinical diagnosis 10-40% advanced melanoma 15-20% at initial diagnosis of advanced melanoma, 50-73% at autopsy 2 Poor prognosis Median survival of 3-7 months 3 Cause of death in 20-55% of advanced melanoma patients Direct cause of death in 95% of cases (high risk for spontaneous hemorrhage) Sperduto P W et al. JCO 2012;30: Carlino, MS et al. PHAMOUS Study, SMR de la Monte, SM et al. Cancer Res, Sampson, JH et al. J Neurosurg, 1998.

13 Prospective Phase II Clinical Trials on Melanoma Brain Metastases presented at the 2017 ASCO AM

14 Prospective Phase II Clinical Trials on Melanoma Brain Metastases presented at the 2017 ASCO AM Study Therapy, Cohorts Tot. No. ORR IC % ORR EC % Gr3/4 AE% Disconti nuation due to AE CMate 204 Ipi/nivo ABC A: Ipi/nivo 26 42* B: Nivo 25 20* C: Nivo Combi-MB (Dabrafenib/ Trametinib) A B C D * 50% and 21% in previously untreated patients

15 Prospective Phase II Clinical Trials on Melanoma Brain Metastases presented at the 2017 ASCO AM Study Therapy, Cohorts Tot. No. ORR IC % ORR EC % Gr3/4 AE% Disconti nuation due to AE CMate 204 Ipi/nivo ABC A: Ipi/nivo 26 42* B: Nivo 25 20* C: Nivo Combi-MB (Dabrafenib/ Trametinib) A B C D * 50% and 21% in previously untreated patients

16 Prospective Phase II Clinical Trials on Melanoma Brain Metastases presented at the 2017 ASCO AM Study Therapy, Cohorts Tot. No. ORR IC % ORR EC % Gr3/4 AE% Disconti nuation due to AE CMate 204 Ipi/nivo ABC A: Ipi/nivo 26 42* B: Nivo 25 20* C: Nivo Combi-MB (Dabrafenib/ Trametinib) A B C D * 50% and 21% in previously untreated patients

17 Management of patients with melanoma brain metastases Safety and results of anti-pd1 combined with radiosurgery for the treatment of melanoma brain metastases [Abstract 9952] 47 pts who received Gamma-knife radiosurgery and anti-pd1 No acute increased risk Incidence, features and management of radionecrosis (RN) in melanoma patients treated with cerebral radiotherapy (RT) and anti-pd-1 antibodies [Abstract No: 9513] Out of 118 pts (with median FU of 24.3 months) 21 pts (18%) developed RN 17% (14/82) after SRS, 9%(2/22) after WBRT and 36% (5/14) after both 78% had neurological symptoms 56% had pathological confirmation of RN Median time to symptom onset and to first radiological sign was 9.8mo and 10.8mo, respectively. 52% were treated with steroids and 30% with bevacizumab, with clinical improvement in 64% and 100%, respectively.

18 Radiation Oncologist Medical Oncologist Neurosurgeon Pathologist Neurologist Neuro-radiologist Palliative Care Treatment of Patients with Melanoma Brain Metastases

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21 Neo-adjuvant Ipi/Nivo and resuming anti-pd-1 (apd1) in patients (pts) with immune-related adverse events Neoadjuvant ipilimumab + nivolumab in palpable stage III melanoma: Updated data from the OpACIN trial and first immunological analyses [Abstract No: 9586]. 18/20 patients had to stop early due to grade 3/4 toxicities Two-arm Phase 1b feasibility trial of 20 high risk AJCC stage IIIB and IIIC melanoma patients with palpable nodal disease receiving the combination of IPI 3mg/kg and NIVO 1mg/kg, either adjuvant 4 courses after surgery, or split 2 courses neo-adjuvant and 2 courses adjuvant Neo-adjuvant application of IPI+NIVO was feasible and no surgery-associated adverse events were attributed to (neo-)adjuvant therapy Neo-adjuvant IPI+NIVO reduced tumor load in 8/10 patients (3 pcr, 4 near-pcrs, 1 ppr, 1 SD and 1 PD) After a median follow-up of 45 weeks (range 13-74), relapse was observed for both non-responders within the neo-adjuvant arm and for 3 patients within the adjuvant arm Safety of resuming anti-pd-1 (apd1) in patients (pts) with immune-related adverse events during combined anti- CTLA-4 (actla4) and apd1 in metastatic melanoma [Abstract No: 9544] 23% experienced recurrence of the same irae with apd1 monotherapy, 16% experienced a distinct irae, and 60% did not experience any severe irae after resuming apd1 64 pts who received apd1 + actla4 for a median of 2 doses (range, 1-4) The most frequent iraes that led to apd1 + actla4 discontinuation were: colitis (36%), hepatitis (23%), hypophysitis (8%), pneumonitis (5%), nephritis (3%), neurologic complications (3%), and pancreatitis (3%); eight pts (13%) had > 1 concurrent severe iraes apd1 was resumed at a median of 55 days after last dose of actla4 + apd1 (range, ) The ORR in this cohort was 73%

22 Checkpoint Inhibition Advanced Melanoma Post ASCO AM When immune checkpoint inhibition is offered to advanced melanoma patients without brain metastases, sequential treatment (starting with anti-p1 monotherapy) avoids exposure to an unnecessary higher risk for irae in 30-40% of the population without a significant difference in overall survival outcome Ensuring sequential exposure to all active treatment options is necessary to optimize survival In patients with melanoma brain metastases who can be managed without steroids, the potential benefit of starting immunotherapy with the IPI+NIVO combination therapy seems to outweights the associated risk for irae

23 New & confirmatory signals of anti-pd(-l)-1 mab activity in CuSCC and MCC REGN2810 (anti-pd-1 mab) has activity in patients with advanced cutaneous squamous cell carcinoma [Abstract #9503] ORR 46% mpfs and mos not reached (medfuof 6.9 mths) No unexpected AE No association between the ORR and level of PD-L1 expression (22C3 clone, Dako) First-line avelumab treatment in pts with metastatic Merkel cell carcinoma [Abstract # 9530] uorr 68.8% (16 pts with 3 months of FU) CR in 18.8%; confirmed ORR 56.3% (95% CI 29 80) All responses ongoing at last follow-up

24 Oncogene T-Cell VEGF- Barrier TME Soluble Factor Atezolizumab + cobimetinib + vemurafenib in BRAF V600mut melanoma [Abstr#: 3063] Anti-LAG-3 (BMS ) [Abst#: 9520] Anti-GITR (BMS ) [Abst#: 104] Anti-CD27 agonist mab (Varlilumab) + NIVO [Abst#: 3007] Avelumab+Axitinib in mrcc [Abst #: 4505] Atezolizumab + bevacizumab in mrcc [Abst#: 3012] Epacadostat + PEMBRO in advanced solid tumors [Abst #: 3012] Inhibition of IDO1 (GDC-0919) and atezolizumab [Abst#: 105] Adenosine A2a receptor (A2aR) antagonist, CPI-444 [Abst#: 3004] CB-1158, a small molecule inhibitor of arginase [Abst#: 3005] M7824 (MSB C) bifunctional fusion protein IgG1 PD-L1 mab fused to the soluble extracellular domain of TGF-β receptor II [Abst#: 3006] T-Cell Excluded Non T-Cell Inflammed Tumor Microenvironment Cold Tumor How to heat a cold tumor? T-Cell Neglected T-VEC plus ipilimumab [Abst#:9509] CEA T-cell bispecific (CEA CD3 TCB) antibody as a single agent and in combination with atezolizumab [Abst#: 3002] NY-ESO-1 specific NY- ESO-1c259t in HLA- A2+ patients with synovial sarcoma [Abst#: 3000] BCMA-Specific CAR T- Cell Therapy in Relapsed/Refractory Multiple Myeloma [Abst#: LBA3001] PEMBRO + CD19- CAR-T cells in relapsed ALL [Abst#: 103] Ibrutinib with personalized cellular therapy (CTL-119) in patients with high-risk CLL [Abst#: 7509] Oncolytic Viral Therapy Bispecific mab Chimeric Antigen Receptor T-Cell Therapy

25 Oncogene T-Cell Atezolizumab + cobimetinib + vemurafenib in BRAF V600mut melanoma [Abstr#: 3063] Anti-LAG-3 (BMS ) [Abst#: 9520] Anti-GITR (BMS ) [Abst#: 104] Anti-CD27 agonist mab (Varlilumab) + NIVO [Abst#: 3007] T-Cell Excluded Non T-Cell Inflammed Tumor Microenvironment Cold Tumor T-Cell Neglected T-VEC plus ipilimumab [Abst#:9509] CEA T-cell bispecific (CEA CD3 TCB) antibody as a single agent and in combination with atezolizumab [Abst#: 3002] Oncolytic Viral Therapy Bispecific mab VEGF- Barrier Avelumab+Axitinib in mrcc [Abst #: 4505] Atezolizumab + bevacizumab in mrcc [Abst#: 3012] NY-ESO-1 specific NY- ESO-1c259t in HLA- A2+ patients with synovial sarcoma [Abst#: 3000] TME Soluble Factor Epacadostat + PEMBRO in advanced solid tumors [Abst #: 3012] Inhibition of IDO1 (GDC-0919) and atezolizumab [Abst#: 105] Adenosine A2a receptor (A2aR) antagonist, CPI-444 [Abst#: 3004] CB-1158, a small molecule inhibitor of arginase [Abst#: 3005] M7824 (MSB C) bifunctional fusion protein IgG1 PD-L1 mab fused to the soluble extracellular domain of TGF-β receptor II [Abst#: 3006] BCMA-Specific CAR T- Cell Therapy in Relapsed/Refractory Multiple Myeloma [Abst#: LBA3001] PEMBRO + CD19- CAR-T cells in relapsed ALL [Abst#: 103] Ibrutinib with personalized cellular therapy (CTL-119) in patients with high-risk CLL [Abst#: 7509] Chimeric Antigen Receptor T-Cell Therapy How to heat a cold tumor?

26 Oncogene T-Cell VEGF- Barrier Atezolizumab + cobimetinib + vemurafenib in BRAF V600mut melanoma [Abstr#: 3063] Anti-LAG-3 (BMS ) [Abst#: 9520] Anti-GITR (BMS ) [Abst#: 104] Anti-CD27 agonist mab (Varlilumab) + NIVO [Abst#: 3007] Avelumab+Axitinib in mrcc [Abst #: 4505] Atezolizumab + bevacizumab in mrcc [Abst#: 3012] T-Cell Excluded Non T-Cell Inflammed Tumor Microenvironment Cold Tumor Anti-PD-1 mab T-Cell Neglected Anti-PD-1 mab T-VEC plus ipilimumab [Abst#:9509] CEA T-cell bispecific (CEA CD3 TCB) antibody as a single agent and in combination with atezolizumab [Abst#: 3002] NY-ESO-1 specific NY- ESO-1c259t in HLA- A2+ patients with synovial sarcoma [Abst#: 3000] Oncolytic Viral Therapy Bispecific mab TME Soluble Factor Epacadostat + PEMBRO in advanced solid tumors [Abst #: 3012] Inhibition of IDO1 (GDC-0919) and atezolizumab [Abst#: 105] Adenosine A2a receptor (A2aR) antagonist, CPI-444 [Abst#: 3004] CB-1158, a small molecule inhibitor of arginase [Abst#: 3005] M7824 (MSB C) bifunctional fusion protein IgG1 PD-L1 mab fused to the soluble extracellular domain of TGF-β receptor II [Abst#: 3006] BCMA-Specific CAR T- Cell Therapy in Relapsed/Refractory Multiple Myeloma [Abst#: LBA3001] PEMBRO + CD19- CAR-T cells in relapsed ALL [Abst#: 103] Ibrutinib with personalized cellular therapy (CTL-119) in patients with high-risk CLL [Abst#: 7509] Chimeric Antigen Receptor T-Cell Therapy How to heat a cold tumor?

27 Non T-Cell Inflammed Tumor Microenvironment Cold Tumor T-Cell Excluded Oncogene T-Cell VEGF- Barrier Atezolizumab + cobimetinib + vemurafenib in BRAF V600mut melanoma [Abstr#: 3063] Anti-LAG-3 (BMS ) [Abst#: 9520] Anti-GITR (BMS ) [Abst#: 104] Anti-CD27 agonist mab (Varlilumab) + NIVO [Abst#: 3007] Avelumab+Axitinib in mrcc [Abst #: 4505] Atezolizumab + bevacizumab in mrcc [Abst#: 3012] Epacadostat + PEMBRO in advanced solid tumors [Abst #: 3012] Inhibition of IDO1 (GDC-0919) and atezolizumab [Abst#: 105] TME Soluble Factor Adenosine A2a receptor (A2aR) antagonist, CPI-444 [Abst#: 3004] CB-1158, a small molecule inhibitor of arginase [Abst#: 3005] M7824 (MSB C) bifunctional fusion protein IgG1 PD-L1 mab fused to the soluble extracellular domain of TGF-β receptor II [Abst#: 3006] Several Phase III ongoing/planned

28 Non T-Cell Inflammed Tumor Microenvironment Cold Tumor T-Cell Excluded Oncogene T-Cell Immune Checkpoint Neovasculature barrier TME Soluble Factor Atezolizumab + cobimetinib + vemurafenib in BRAF V600mut melanoma [Abstr#: 3063] Anti-LAG-3 (BMS ) [Abst#: 9520] Anti-GITR agonist mab (BMS ) [Abst#: 104] Anti-CD27 agonist mab (Varlilumab) + NIVO [Abst#: 3007] Avelumab+Axitinib in mrcc [Abst #: 4505] Atezolizumab + bevacizumab in mrcc [Abst#: 3012] Epacadostat + PEMBRO in advanced solid tumors [Abst #: 3012] Inhibition of IDO1 (GDC-0919) and atezolizumab [Abst#: 105] Adenosine A2a receptor (A2aR) antagonist, CPI-444 [Abst#: 3004] CB-1158, a small molecule inhibitor of arginase [Abst#: 3005] M7824 (MSB C) bifunctional fusion protein IgG1 PD-L1 mab fused to the soluble extracellular domain of TGF-β receptor II [Abst#: 3006]

29 Non T-Cell Inflammed Tumor Microenvironment Cold Tumor T-Cell Excluded Oncogene T-Cell Immune Checkpoint Neovasculature barrier Atezolizumab + cobimetinib + vemurafenib in BRAF V600mut melanoma [Abstr#: 3063] Anti-LAG-3 (BMS ) [Abst#: 9520] Anti-GITR agonist mab (BMS ) [Abst#: 104] Anti-CD27 agonist mab (Varlilumab) + NIVO [Abst#: 3007] Avelumab+Axitinib in mrcc [Abst #: 4505] Atezolizumab + bevacizumab in mrcc [Abst#: 3012] TME Soluble Factor Epacadostat + PEMBRO in advanced solid tumors [Abst #: 3012] Inhibition of IDO1 (GDC-0919) and atezolizumab [Abst#: 105] Adenosine A2a receptor (A2aR) antagonist, CPI-444 [Abst#: 3004] CB-1158, a small molecule inhibitor of arginase [Abst#: 3005] M7824 (MSB C) bifunctional fusion protein IgG1 PD-L1 mab fused to the soluble extracellular domain of TGF-β receptor II [Abst#: 3006]

30 Non T-Cell Inflammed Tumor Microenvironment Cold Tumor T-Cell Excluded Oncogene T-Cell Immune Checkpoint Neovasculature barrier TME Soluble Factor Atezolizumab + cobimetinib + vemurafenib in BRAF V600mut melanoma [Abstr#: 3063] Anti-LAG-3 (BMS ) [Abst#: 9520] Anti-GITR agonist mab (BMS ) [Abst#: 104] Anti-CD27 agonist mab (Varlilumab) + NIVO [Abst#: 3007] Avelumab+Axitinib in mrcc [Abst #: 4505] Atezolizumab + bevacizumab in mrcc [Abst#: 3012] Epacadostat + PEMBRO in advanced solid tumors [Abst #: 3012] Inhibition of IDO1 (GDC-0919) and atezolizumab [Abst#: 105] Adenosine A2a receptor (A2aR) antagonist, CPI-444 [Abst#: 3004] CB-1158, a small molecule inhibitor of arginase [Abst#: 3005] M7824 (MSB C) bifunctional fusion protein IgG1 PD-L1 mab fused to the soluble extracellular domain of TGF-β receptor II [Abst#: 3006]

31 Non T-Cell Inflammed Tumor Microenvironment Cold Tumor T-Cell Excluded Oncogene T-Cell Immune Checkpoint Neovasculature barrier TME Soluble Factor Atezolizumab + cobimetinib + vemurafenib in BRAF V600mut melanoma [Abstr#: 3063] Anti-LAG-3 (BMS ) [Abst#: 9520] Anti-GITR agonist mab (BMS ) [Abst#: 104] Anti-CD27 agonist mab (Varlilumab) + NIVO [Abst#: 3007] Avelumab+Axitinib in mrcc [Abst #: 4505] Atezolizumab + bevacizumab in mrcc [Abst#: 3012] Epacadostat + PEMBRO in advanced solid tumors [Abst #: 3012] Inhibition of IDO1 (GDC-0919) and atezolizumab [Abst#: 105] CB-1158, a small molecule inhibitor of arginase [Abst#: 3005] Adenosine A2a receptor (A2aR) antagonist, CPI-444 [Abst#: 3004] M7824 (MSB C) bifunctional fusion protein IgG1 PD-L1 mab fused to the soluble extracellular domain of TGF-β receptor II [Abst#: 3006]

32 Non T-Cell Inflammed Tumor Microenvironment Cold Tumor T-Cell Excluded Oncogene T-Cell Immune Checkpoint Neovasculature barrier TME Soluble Factor Atezolizumab + cobimetinib + vemurafenib in BRAF V600mut melanoma [Abstr#: 3063] Anti-LAG-3 (BMS ) [Abst#: 9520] Anti-GITR agonist mab (BMS ) [Abst#: 104] Anti-CD27 agonist mab (Varlilumab) + NIVO [Abst#: 3007] Avelumab+Axitinib in mrcc [Abst #: 4505] Atezolizumab + bevacizumab in mrcc [Abst#: 3012] Epacadostat + PEMBRO in advanced solid tumors [Abst #: 3012] Inhibition of IDO1 (GDC-0919) and atezolizumab [Abst#: 105] CB-1158, a small molecule inhibitor of arginase [Abst#: 3005] Adenosine A2a receptor (A2aR) antagonist, CPI-444 [Abst#: 3004] M7824 (MSB C) bifunctional fusion protein IgG1 PD-L1 mab fused to the soluble extracellular domain of TGF-β receptor II [Abst#: 3006] Phase III ongoing/planned

33 Non T-Cell Inflammed Tumor Microenvironment Cold Tumor T-Cell Excluded Oncogene T-Cell Immune Checkpoint Neovasculature barrier TME Soluble Factor Atezolizumab + cobimetinib + vemurafenib in BRAF V600mut melanoma [Abstr#: 3063] Anti-LAG-3 (BMS ) [Abst#: 9520] Anti-GITR agonist mab (BMS ) [Abst#: 104] Anti-CD27 agonist mab (Varlilumab) + NIVO [Abst#: 3007] Avelumab+Axitinib in mrcc [Abst #: 4505] Atezolizumab + bevacizumab in mrcc [Abst#: 3012] Epacadostat + PEMBRO in advanced solid tumors [Abst #: 3012] Inhibition of IDO1 (GDC-0919) and atezolizumab [Abst#: 105] CB-1158, a small molecule inhibitor of arginase [Abst#: 3005] Adenosine A2a receptor (A2aR) antagonist, CPI-444 [Abst#: 3004] M7824 (MSB C) bifunctional fusion protein IgG1 PD-L1 mab fused to the soluble extracellular domain of TGF-β receptor II [Abst#: 3006]

34 Non T-Cell Inflammed Tumor Microenvironment Cold Tumor T-Cell Excluded Oncogene T-Cell Immune Checkpoint Neovasculature barrier TME Soluble Factor Atezolizumab + cobimetinib + vemurafenib in BRAF V600mut melanoma [Abstr#: 3063] Anti-LAG-3 (BMS ) [Abst#: 9520] Anti-GITR agonist mab (BMS ) [Abst#: 104] Anti-CD27 agonist mab (Varlilumab) + NIVO [Abst#: 3007] Avelumab+Axitinib in mrcc [Abst #: 4505] Atezolizumab + bevacizumab in mrcc [Abst#: 3012] Epacadostat + PEMBRO in advanced solid tumors [Abst #: 3012] Inhibition of IDO1 (GDC-0919) and atezolizumab [Abst#: 105] CB-1158, a small molecule inhibitor of arginase [Abst#: 3005] Adenosine A2a receptor (A2aR) antagonist, CPI-444 [Abst#: 3004] M7824 (MSB C) bifunctional fusion protein IgG1 PD-L1 mab fused to the soluble extracellular domain of TGF-β receptor II [Abst#: 3006]

35 Non T-Cell Inflammed Tumor Microenvironment Cold Tumor T-Cell Neglected Oncolytic Viral Therapy Bispecific mab Chimeric Antigen Receptor T-Cell Therapy T-VEC plus ipilimumab [Abst#:9509] CEA T-cell bispecific (CEA CD3 TCB) antibody as a single agent and in combination with atezolizumab [Abst#: 3002] NY-ESO-1 specific NY-ESO- 1c259t in HLA- A2+ patients with synovial sarcoma [Abst#: 3000] BCMA-Specific CAR T-Cell Therapy in Relapsed/Refractory Multiple Myeloma [Abst#: LBA3001] PEMBRO + CD19- CAR-T cells in relapsed ALL [Abst#: 103] Ibrutinib with personalized cellular therapy (CTL-119) in patients with high-risk CLL [Abst#: 7509]

36 Non T-Cell Inflammed Tumor Microenvironment Cold Tumor T-Cell Neglected Oncolytic Viral Therapy Bispecific mab Chimeric Antigen Receptor T-Cell Therapy T-VEC plus ipilimumab [Abst#:9509] CEA T-cell bispecific (CEA CD3 TCB) antibody as a single agent and in combination with atezolizumab [Abst#: 3002] NY-ESO-1 specific NY-ESO- 1c259t in HLA- A2+ patients with synovial sarcoma [Abst#: 3000] BCMA-Specific CAR T-Cell Therapy in Relapsed/Refractory Multiple Myeloma [Abst#: LBA3001] PEMBRO + CD19- CAR-T cells in relapsed ALL [Abst#: 103] Ibrutinib with personalized cellular therapy (CTL-119) in patients with high-risk CLL [Abst#: 7509]

37 Non T-Cell Inflammed Tumor Microenvironment Cold Tumor T-Cell Neglected Oncolytic Viral Therapy Bispecific mab Chimeric Antigen Receptor T-Cell Therapy T-VEC plus ipilimumab [Abst#:9509] CEA T-cell bispecific (CEA CD3 TCB) antibody as a single agent and in combination with atezolizumab [Abst#: 3002] NY-ESO-1 specific NY-ESO- 1c259t in HLA- A2+ patients with synovial sarcoma [Abst#: 3000] BCMA-Specific CAR T-Cell Therapy in Relapsed/Refractory Multiple Myeloma [Abst#: LBA3001] PEMBRO + CD19- CAR-T cells in relapsed ALL [Abst#: 103] Ibrutinib with personalized cellular therapy (CTL-119) in patients with high-risk CLL [Abst#: 7509]

38 Non T-Cell Inflammed Tumor Microenvironment Cold Tumor T-Cell Neglected Oncolytic Viral Therapy Bispecific mab Chimeric Antigen Receptor T-Cell Therapy T-VEC plus ipilimumab [Abst#:9509] CEA T-cell bispecific (CEA CD3 TCB) antibody as a single agent and in combination with atezolizumab [Abst#: 3002] NY-ESO-1 specific NY-ESO- 1c259t in HLA- A2+ patients with synovial sarcoma [Abst#: 3000] BCMA-Specific CAR T-Cell Therapy in Relapsed/Refractory Multiple Myeloma [Abst#: LBA3001] PEMBRO + CD19- CAR-T cells in relapsed ALL [Abst#: 103] Ibrutinib with personalized cellular therapy (CTL-119) in patients with high-risk CLL [Abst#: 7509]

39 Time for precision immuno-oncology? Tumor agnostic development?

40

41 Anti-PD-1 mab

42 Thank you for your attention!