Table 1.

Selected clinical trials investigating novel immune, TME, and host-modulating drug combinations for PDAC treatment

Drug combinations	Chemotherapy	ICB	Mechanism of additional agent(s)	Phase	N	Population	Clinical trial
Ciprofloxacin + gemcitabine + nab-paclitaxel	Yes	No	Ciprofloxacin: Targeting the microbiome	Phase I	10	Metastatic PDAC	NCT04523987
BMS-813160 + nivolu­mab + gemcitabine + nab-paclitaxel	Yes	Anti–PD-1	BMS-813160: CCR2/CCR5 antagonist	Phase I/II	40	PDAC	NCT03496662
GEN1042 + pembrolizu­mab ± gemcitabine + nab-paclitaxel	Yes	Anti–PD-1	GEN1042: Bispecific agonistic antibody targeting CD40/4-1BB	Phase I/II	447	Malignant solid tumors, including PDAC	NCT04083599
NZV930 + spartalizumab ± NIR178	No	Anti–PD-1	NZV930: CD73 antagonist; NIR178: adenosine 2A receptor antagonist	Phase I	344	Malignant solid tumors, including PDAC	NCT03549000
Atorvastatin + ezetimibe + evolocu­mab + FOLFIRINOX	Yes	No	Atorvastatin, ezetimibe, evolocumab: Cholesterol metabolism disruption	Early phase I	12	Metastatic PDAC	NCT04862260
SX-682 + nivolumab	No	Anti–PD-1	SX-682: CXCR1/2 antagonist	Phase I	20	PDAC	NCT04477343
MEDI4736 + nab-paclitaxel + gemcitabine or MEDI4736 + AZD5069	Yes	Anti–PD-L1	AZD5069: CXCR2 antagonist	Phase I/II	23	Metastatic PDAC	NCT02583477
Different combinations of the following compounds: nab-paclitaxel ± gemcitabine ± oxaliplatin ± leucovorin ± fluorouracil ± atezolizumab ± cobimetinib ± PEGPH20 ± BL-8040 ± selicrelumab ± bevacizumab ± RO6874281 ± AB928 ± tiragolumab ± tocilizumab	Yes	Anti–PD-L1 + anti-TIGIT	Cobimetinib: MEK inhibitor; PEGPH20: ECM targeting; BL-8040: CXCR4 antagonist; selicrelumab: CD40 agonist; bevacizumab: VEGF inhibitor; RO6874281: engineered variant of IL2 (IL2v) targeted to tumor-associated fibroblasts via binding to FAP; AB928: dual adenosine receptor antagonist; tocilizumab: IL6 receptor	Phase I/II	290	PDAC	NCT03193190
Fecal microbiota transplantation	No	No	Patients undergo fecal microbiota transplantation during colonoscopy	Early phase I	10	PDAC	NCT04975217
L-glutamine + gemcitabine + nab-paclitaxel	Yes	No	L-glutamine: Metabolism	Phase I	16	Advanced PDAC	NCT04634539
Canakinumab + spartalizu­mab + nab-paclitaxel + gemcitabine	Yes	Anti–PD-1	Canakinumab: Anti-IL1β monoclonal antibody	Phase I	10	Metastatic PDAC	NCT04581343
CAN04 ± gemcitabine + nab-paclitaxel	Yes	No	CAN04: IL1 receptor accessory protein (IL1RAP)	Phase I/II	140	Malignant solid tumors, including PDAC	NCT03267316
NGM707 ± pembrolizumab	No	Anti–PD-1	NGM707: ILT2/ILT4 antagonist	Phase I/II	179	Malignant solid tumors, including PDAC	NCT04913337
Regorafenib + nivolumab	No	Anti–PD-1	Regorafenib: Multi-RTK inhibitor	Phase II	175	Malignant solid tumors, including PDAC	NCT04704154
IACS-010759	No	No	IACS-010759: Oxidative phosphorylation inhibitor	Phase I	29	Malignant solid tumors, including PDAC	NCT03291938
NIS793 ± spartalizu­mab + gemcitabine + nab-paclitaxel	Yes	Anti–PD-1	NIS793: TGFB1 inhibitor	Phase II	161	Metastatic PDAC	NCT04390763
Personalized peptide vaccine ± imiquimod ± pembrolizumab ± sotigalimab	No	Anti–PD-1	Imiquimod: Toll-like receptor 7 agonist; sotigalimab: CD40 agonist	Phase I	150	Malignant solid tumors, including advanced PDAC	NCT02600949
Ascorbic acid + nab-paclitaxel + cis­platin + gemcitabine	Yes	No	Administration of high-dose IV vitamin C	Phase I/II	27	Advanced PDAC	NCT03410030
Paricalcitol + hydroxychloroquine + losartan	Yes	No	Paricalcitol: Vitamin D analogue; hydroxychloroquine: autophagy; losartan: angiotensin II receptor antagonist	Early phase I	20	PDAC	NCT05365893
Paricalcitol + nab-paclitaxel + cis­platin + gemcitabine	Yes	No	Paricalcitol: Vitamin D analogue	Phase II	14	Advanced PDAC	NCT03415854

Abbreviation: RTK, receptor tyrosine kinase.