Immunotherapy for pancreatic cancer

Table 2 Clinical outcomes of immunotherapies in advanced pancreatic cancer

Study drug	Ref.	Clinical setting	Therapeutic protocol	Study phase	Number of patients	Outcomes	Adverse events (Grade 3 or 4)
Anti-CTLA-4 antibodies
Ipilimumab	Royal et al[42], 2010	Locally advanced or metastatic	Ipilimumab only	II	27	ORR: 0%, but one delayed tumor regression after initial progression	11.1% (3/27; 1 fatal pneumonia, 1 confusion and lethargy, 1 hypophysitis)
Ipilimumab	Kamath et al[66], 2020	Locally advanced or metastatic	Gemcitabine + Ipilimumab	Ib	21	ORR: 14% (3/21). PFS: 2.78 mo. OS: 6.90 mo	76.2% (16/21; elevated ALT, diarrhea, mostly hematologic toxicity)
Anti-PD-1 antibodies and anti-PD-L1 antibodies
Pembrolizumab	Le et al[46], 2017	Solid tumor with MSI-h	Pembrolizumab only	II	8 (all cancer 86)	ORR: 53% in solid tumor with MSI-h	N-A (mostly low grade)
Pembrolizumab	Weiss et al[68], 2018	Metastatic	Gemcitabine + Nab-paclitaxel + Pembrolizumab	Ib/II	17	PFS: 9.1 mo. OS: 15.0 mo	70.6% (12/17)
Nivolumab	Wainberg et al[67], 2020	Locally advanced or metastatic	Gemcitabine + Nab-paclitaxel + Nivolumab	I	50	ORR: 18%. PFS: 5.5 mo. OS: 9.9 mo	36.0% (18/50; peripheral neuropathy, hypokalemia, diarrhea, increased AST/ALT, mostly hematologic toxicity)
Durvalumab	Renouf, 2020 (abstract)	Metastatic	Gemcitabine + Nab-paclitaxel + Durvalumab + Tremelimumab vsGemcitabine + Nab-paclitaxel	II	119 vs 61	ORR: 30.3% vs 23.0%. PFS: 5.5 mo vs 5.4 mo. OS: 9.8 mo vs 8.8 mo	N-A
CAR T cell immunotherapy
Mesothelin-specific	Beatty et al[51], 2018	Metastatic	Mesothelin-specific CAR T cells	I	6	Disease stabilized: 2 patients (33%) with PFS of 3.8 and 5.4 mo	0% (0/6)
Vaccine-based immunotherapy
GV1001	Middleton et al[54], 2014	Locally advanced or metastatic	Gemcitabine + Capecitabine vs Gemcitabine + Capecitabine with sequential GV1001 vs Gemcitabine + Capecitabine with concurrent GV1001	III	358 vs 350 vs 354	OS: 7.9 mo vs 6.9 mo vs 8.4 mo	13.1% vs 12.6% vs 12.4%
GVAX	Le et al[56], 2019	Metastatic, previously treated	Cy/GVAX + CRS-207 vs CRS-207 vs Single-agent chemotherapy	IIb	73 vs 68 vs 72	OS: 3.7 mo vs 5.4 mo vs 4.6 mo	46.8% vs 36.8% vs 27.8%
GVAX	Wu et al[55], 2020	Metastatic	GVAX + Ipilimumab after FOLFIRINOX vs FOLFIRINOX continuation	II	40 vs 42	PFS: 2.4 mo vs 5.55 mo. OS: 9.38 mo vs 14.7 mo	41.0% (16/39; adrenal insufficiency, hypophysitis, rash, diarrhea)

ORR: Objective response rate; OS: Overall survival (median); PFS: Progression free survival (median); GV1001: Telomerase reverse transcriptase catalytic subunit class II 16mer peptide vaccine; GVAX: Granulocyte-macrophage colony-stimulating factor-transfected pancreatic tumor vaccine; Cy: Cyclophosphamide; CRS-207: Live attenuated Listeria monocytogenes expressing mesothelin; PD-1: Programmed cell death 1; ALT: Alternative lengthening of telomeres; AST: Aspartate aminotransferase; CAR: Chimeric antigen receptor; CTLA-4: Cytotoxic T lymphocyte-associated protein 4; MSI-h: Microsatellite instability-high; PD-L1: Programmed cell death ligand 1.