Immune therapies in pancreatic ductal adenocarcinoma: Where are we now?

Table 1 Summary of clinical trials of immune therapies (single agent or combination with gemcitabine) in patients with pancreatic ductal adenocarcinoma

Type of immunotherapy	Molecules	Trial	Phase	n	Population	Main results
Immune checkpoint inhibitors	PD-L1 (BMS-936559)	Brahmer et al[8]	I	14	Advanced PDAC Pre-treated	No objective response
	PD-L1 (atezolizumab)	Herbst et al[12]	I	1	Advanced PDAC Pre-treated	No objective response
	PD-1 (pembrolizumab)	Patnaik et al[13]	I	1	Advanced PDAC Pre-treated	No objective response
	CTLA-4 (ipilimumab)	Royal et al[14]	II	27	Advanced PDAC Pre-treated	No objective response
Therapeutic vaccines	GVAX	Jaffee et al[118]	I	14	Resected PDAC Adjuvant Combination with chemoradiotherapy	3 patients remained disease-free for > 25 mo
		Lutz et al[119]	II	60	Resected PDAC Adjuvant Combination with chemoradiotherapy	Median disease-free survival: 17.3 mo Median overall survival: 24.8 mo
		Laheru et al[120]	II	50	Advanced PDAC Pre-treated Combination with cyclophosphamide	Median overall survival: 4.3 mo
		Lutz et al[30]	Pilot Randomized	54	Resected PDAC Neoadjuvant and adjuvant Combination with cyclophosphamide	Arm 1: GVAX alone Arm 2: Cyclophosphamide (intravenous) + GVAX Arm 3: Cyclophosphamide (daily oral) + GVAX Intra-tumoral tertiary lymphoid aggregates PD-1 and PDL-1 upregulation
	CRS 207	Le et al[121]	I	7	Advanced PDAC Pre-treated	No objective response
	GVAX + CRS 207	Le et al[78]	II Randomized	90	Advanced PDAC Pre-treated	Arm 1: Cyclophosphamide + GVAX + CRS-207 Arm 2: Cyclophosphamide + GVAX No objective response
	Algenpantucel-L	Hardacre et al[122]	II	70	Resected PDAC Adjuvant Combination with chemotherapy	Disease-free survival: 62% at 1 yr Overall survival: 86% at 1 yr
	Mutated KRAS peptide	Gjertsen et al[123]	I/II	5	Advanced PDAC Pre-treated	No objective response
		Gjertsen et al[124]	I/II	48	Advanced PDAC Pre-treated Resected PDAC Adjuvant	No objective response Median overall survival in resected PDAC: 25.6 mo
		Abou-Alfa et al[125]	I	24	Resected PDAC Adjuvant	Median disease-free survival: 8.6 mo Median overall survival: 20.3 mo
	Telomerase peptide (GV1001)	Middleton et al[126]	III Randomized	1062	Advanced PDAC First line Combination with chemotherapy	Arm 1: chemotherapy alone Arm 2: sequential chemo-immunotherapy Arm 3: concurrent chemo-immunotherapy No benefit on overall survival of adding vaccination to chemotherapy
Oncolytic viruses	Mutated adenovirus (ONYX-15)	Hecht et al[127]	I/II	21	Advanced PDAC Pre-treated and first line Combination with chemotherapy	Two partial responses
		Mulvihill et al[128]	I	23	Advanced PDAC Pre-treated and first line	No objective response
Anti-transforming growth factor β (TGFβ)	Anti-TGFβ2 (trabedersen)	Oettle et al[129]	I/II	37	Advanced PDAC Pre-treated	One complete response
	TGFβ receptor inhibitor (galunisertib)	Melisi et al[130]	II Randomized	156	Advanced PDAC Pre-treated and first line Combination with chemotherapy	Arm 1: galunisertib + gemcitabine Arm 2: gemcitabine +placebo No benefit on overall survival of adding galunisertib to chemotherapy

CTLA-4: Cytotoxic T lymphocyte-associated protein 4; PD-1: Programmed cell death-1; PD-L1: Programmed death-ligand 1.