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(1)

TUMORI GASTROINTESTINALI - NUOVE PROSPETTIVE -

Dr. Armando Orlandi

(2)

• Consensus molecular subtypes (CMS) in CRC

• CMS background

• CMS and FIRE-3/CALGB (ASCO17)

• CMS and MAX (ESMO17)

• Immunotherapy and GI cancer

• CMS1CMS4 and Immunotherapy strategies

• GEJ and Immunotherapy

• New drugs in Pancreatic cancer

• Eryaspase (phase II study)

• CPI-613 (phase I study)

OUTLINE

Tumori Gastrointestinali – Nuove Prospettive –

Roma, 7 ottobre 2017 Dr. Armando Orlandi

(3)

Consensus molecular subtypes (CMS) in CRC

• CMS background

• CMS and FIRE-3/CALGB (ASCO17)

• CMS and MAX (ESMO17)

• Immunotherapy and GI cancer

• CMS1CMS4 and Immunotherapy strategies

• GEJ and Immunotherapy

• New drugs in Pancreatic cancer

• Eryaspase (phase II study)

• CPI-613 (phase I study)

OUTLINE

Tumori Gastrointestinali – Nuove Prospettive –

Roma, 7 ottobre 2017 Dr. Armando Orlandi

(4)

Consensus molecular subtypes (CMS) in CRC

CMS background

(5)

Guinney J. et al, Nat Med 2015

Consensus molecular subtypes (CMS) in CRC

CMS background

(6)

Guinney J. et al, Nat Med 2015

CMS1 CMS2 CMS3 CMS4

Consensus molecular subtypes (CMS) in CRC

CMS background

(7)

Consensus molecular subtypes (CMS) in CRC

CMS and FIRE-3/CALGB (ASCO17)

(8)

Consensus molecular subtypes (CMS) in CRC

CMS and FIRE-3 (ASCO17)

(9)

Consensus molecular subtypes (CMS) in CRC

CMS and CALGB (ASCO17)

(10)

Consensus molecular subtypes (CMS) in CRC

CMS and FIRE-3(ASCO17)

(11)

Consensus molecular subtypes (CMS) in CRC

CMS and CALGB (ASCO17)

(12)

Consensus molecular subtypes (CMS) in CRC

CMS and FIRE-3 vs CALGB (ASCO17)

CMS1

CMS2

CMS3

CMS4

X

X

FIRE- 3

CALGB

(13)

Consensus molecular subtypes (CMS) in CRC

CMS and MAX trial (ESMO17)

(14)

Consensus molecular subtypes (CMS) in CRC

CMS and MAX trial (ESMO17)

(15)

J. Mooi et al. ESMO17

Consensus molecular subtypes (CMS) in CRC

CMS and MAX trial (ESMO17)

(16)

J. Mooi et al. ESMO17

Consensus molecular subtypes (CMS) in CRC

CMS and MAX trial (ESMO17)

(17)

J. Mooi et al. ESMO17

Consensus molecular subtypes (CMS) in CRC

CMS and MAX trial (ESMO17)

(18)

• Prognostic value of CMS in CRC.

• Different prognostic value of CMS in mCRC vs adjCRC.

• CMS1 best prognosis in adjCRC and worst prognosis in mCRC.

• CMS2 best prognosis in mCRC.

• Not clear predictive role of CMS for Cetuximab or Bevacizumab.

Consensus molecular subtypes (CMS) in CRC

CONCLUSION

(19)

• Consensus molecular subtypes (CMS) in CRC

• CMS background

• CMS and FIRE-3/CALGB (ASCO17)

• CMS and MAX (ESMO17)

Immunotherapy and GI cancer

CMS and Immunotherapy strategies

• GEJ and Immunotherapy

• New drugs in Pancreatic cancer

• Eryaspase (phase II study)

• CPI-613 (phase I study)

OUTLINE

Tumori Gastrointestinali – Nuove Prospettive –

Roma, 7 ottobre 2017 Dr. Armando Orlandi

(20)

Immunotherapy and GI cancer

CMS and Immunotherapy strategies

CMS4 Mesenchymal CMS1

MSI - Immune

CMS2 Canonical

CMS3 Metabolic

(21)

Immunotherapy and GI cancer

CMS and Immunotherapy strategies

(22)

D.T. Le et al. NEJM 2015

Immunotherapy and GI cancer

CMS1 and Immunotherapy strategies

Overman et al. Lancet 2017

(23)

D.T. Le et al. NEJM 2015

Immunotherapy and GI cancer

CMS1 and Immunotherapy strategies

Overman et al. Lancet 2017

(24)

Immunotherapy and GI cancer

CMS2-3-4 and Immunotherapy strategies

Strategy: PD1 blockade +MEK inhibitors or chemotherapy or TCBs?

(25)

Immunotherapy and GI cancer

CMS2-3 and Immunotherapy strategies

(26)

Immunotherapy and GI cancer

CMS2-3 and Immunotherapy strategies

(27)

Immunotherapy and GI cancer

CMS4 and Immunotherapy strategies

(28)

Immunotherapy and GI cancer

CMS4 and Immunotherapy strategies

(29)

• Consensus molecular subtypes (CMS) in CRC

• CMS background

• CMS and FIRE-3/CALGB (ASCO17)

• CMS and MAX (ESMO17)

Immunotherapy and GI cancer

• CMS and Immunotherapy strategies

GEJ and Immunotherapy

• New drugs in Pancreatic cancer

• Eryaspase (phase II study)

• CPI-613 (phase I study)

OUTLINE

Tumori Gastrointestinali – Nuove Prospettive –

Roma, 7 ottobre 2017 Dr. Armando Orlandi

(30)

Immunotherapy and GI cancer

GJE and Immunotherapy strategies

(31)

Immunotherapy and GI cancer

GJE and Immunotherapy strategies

Z. Wainberg et al., ESMO 2017

(32)

Z. Wainberg et al., ESMO 2017

Immunotherapy and GI cancer

GJE and Immunotherapy strategies

(33)

Z. Wainberg et al., ESMO 2017

Immunotherapy and GI cancer

GJE and Immunotherapy strategies

(34)

Z. Wainberg et al., ESMO 2017

Immunotherapy and GI cancer

GJE and Immunotherapy strategies

(35)

Z. Wainberg et al., ESMO 2017

Immunotherapy and GI cancer

GJE and Immunotherapy strategies

(36)

Z. Wainberg et al., ESMO 2017

Immunotherapy and GI cancer

GJE and Immunotherapy strategies

(37)

Z. Wainberg et al., ESMO 2017

Immunotherapy and GI cancer

GJE and Immunotherapy strategies

(38)

• Consensus molecular subtypes (CMS) in CRC

• CMS background

• CMS and FIRE-3/CALGB (ASCO17)

• CMS and MAX (ESMO17)

• Immunotherapy and GI cancer

• CMS1CMS4 and Immunotherapy strategies

• GEJ and Immunotherapy

New drugs in Pancreatic cancer

• Eryaspase (phase II study)

• CPI-613 (phase I study)

OUTLINE

Tumori Gastrointestinali – Nuove Prospettive –

Roma, 7 ottobre 2017 Dr. Armando Orlandi

(39)

Hammel et al. ESMO 2017

New drugs in Pancreatic cancer

A Phase 2b of eryaspase in combination with gemcitabine or FOLFOX as second-line therapy in patients with metastatic pancreatic adenocarcinoma

(40)

Hammel et al. ESMO 2017

New drugs in Pancreatic cancer

A Phase 2b of eryaspase in combination with gemcitabine or FOLFOX as second-line therapy in patients with metastatic pancreatic adenocarcinoma

(41)

New drugs in Pancreatic cancer

1733PD - New promising combination therapy of a mitochondrial metabolism inhibitor with mFOLFIRINOX in pancreatic cancer

(42)

New drugs in Pancreatic cancer

1733PD - New promising combination therapy of a mitochondrial metabolism inhibitor with mFOLFIRINOX in pancreatic cancer

(43)

• Interesting activity in phase 1 study of innovative combination.

• Confirmation in phase III study is warranted.

• New target therapy.

New drugs in Pancreatic cancer

1733PD - New promising combination therapy of a mitochondrial metabolism inhibitor with mFOLFIRINOX in pancreatic cancer

• Metabolic therapy ERA?

(44)

armando.orlandi@policlinicogemelli.it

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