Nuove prospettive

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TUMORI GASTROINTESTINALI - NUOVE PROSPETTIVE -

Dr. Armando Orlandi

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• 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

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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

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Consensus molecular subtypes (CMS) in CRC

CMS background

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Guinney J. et al, Nat Med 2015

Consensus molecular subtypes (CMS) in CRC

CMS background

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Guinney J. et al, Nat Med 2015

CMS1 CMS2 CMS3 CMS4

Consensus molecular subtypes (CMS) in CRC

CMS background

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Consensus molecular subtypes (CMS) in CRC

CMS and FIRE-3/CALGB (ASCO17)

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Consensus molecular subtypes (CMS) in CRC

CMS and FIRE-3 (ASCO17)

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Consensus molecular subtypes (CMS) in CRC

CMS and CALGB (ASCO17)

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Consensus molecular subtypes (CMS) in CRC

CMS and FIRE-3(ASCO17)

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Consensus molecular subtypes (CMS) in CRC

CMS and CALGB (ASCO17)

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Consensus molecular subtypes (CMS) in CRC

CMS and FIRE-3 vs CALGB (ASCO17)

CMS1

CMS2

CMS3

CMS4



X

FIRE- 3

CALGB

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Consensus molecular subtypes (CMS) in CRC

CMS and MAX trial (ESMO17)

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Consensus molecular subtypes (CMS) in CRC

CMS and MAX trial (ESMO17)

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J. Mooi et al. ESMO17

Consensus molecular subtypes (CMS) in CRC

CMS and MAX trial (ESMO17)

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Consensus molecular subtypes (CMS) in CRC

CMS and MAX trial (ESMO17)

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Consensus molecular subtypes (CMS) in CRC

CMS and MAX trial (ESMO17)

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• 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

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• 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

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Immunotherapy and GI cancer

CMS and Immunotherapy strategies

CMS4 Mesenchymal CMS1

MSI - Immune

CMS2 Canonical

CMS3 Metabolic

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Immunotherapy and GI cancer

CMS and Immunotherapy strategies

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D.T. Le et al. NEJM 2015

Immunotherapy and GI cancer

CMS1 and Immunotherapy strategies

Overman et al. Lancet 2017

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D.T. Le et al. NEJM 2015

Immunotherapy and GI cancer

CMS1 and Immunotherapy strategies

Overman et al. Lancet 2017

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Immunotherapy and GI cancer

CMS2-3-4 and Immunotherapy strategies

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

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Immunotherapy and GI cancer

CMS2-3 and Immunotherapy strategies

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Immunotherapy and GI cancer

CMS2-3 and Immunotherapy strategies

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Immunotherapy and GI cancer

CMS4 and Immunotherapy strategies

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Immunotherapy and GI cancer

CMS4 and Immunotherapy strategies

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• 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

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Immunotherapy and GI cancer

GJE and Immunotherapy strategies

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Immunotherapy and GI cancer

GJE and Immunotherapy strategies

Z. Wainberg et al., ESMO 2017

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Immunotherapy and GI cancer

GJE and Immunotherapy strategies

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Immunotherapy and GI cancer

GJE and Immunotherapy strategies

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Immunotherapy and GI cancer

GJE and Immunotherapy strategies

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Immunotherapy and GI cancer

GJE and Immunotherapy strategies

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Immunotherapy and GI cancer

GJE and Immunotherapy strategies

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Immunotherapy and GI cancer

GJE and Immunotherapy strategies

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• 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

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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

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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

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New drugs in Pancreatic cancer

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

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New drugs in Pancreatic cancer

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• Interesting activity in phase 1 study of innovative combination.

• Confirmation in phase III study is warranted.

• New target therapy.

New drugs in Pancreatic cancer

• Metabolic therapy ERA?

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