Table 2.

Clinical trials targeting autophagy/lysosome in pancreatic cancer

Disease	Interventions	Results	Study phase	Refs
Previously treated, Meatastatic	HCQ	0% response	II	NCT01273805 [126]
Borderline resectable	Gem + HCQ (neoadjuvant)	CA19-9 decrease in 61% cases; R0 resection in 77% cases; Prolonged OS in patients with significant autophagy inhibition in peripheral blood cells (34.83 vs 10.83 months, p < 0.05)	I/II	NCT01128296 [137]
Metastatic or unresectable	Gem + CQ	Median PFS, 4 months; Median OS, 7.6 months	I	NCT01777477 [138]
Previously untreated, metastatic or Advanced	GnP ± HCQ	Improved RR in GnP with HCQ than in GnP without HCQ (38.2 vs 21.1%); no difference in OS and PFS	I/II	NCT01506973 [127]
Resectable or borderline resectable	GnP ± HCQ (neoadjuvant)	Addition of HCQ to GnP improved histopathologic RR (p = 0.00016) and tumor infiltrating CD8 + T cells. Intratumoral αβ T cell receptor clonality was associated with CA 19–9 response and prolonged OS	II	NCT01978184 [103] [104]
Previously untreated, Metastatic	GnP + HCQ + Ipilimumab (anti-CTLA4 antibody)	Ongoing	I	NCT04787991
Gastrointestinal cancer (pancreatic and colorectal cancer)	Cobimetinib (MEK inhibitor) + Atezolizumab (anti-PDL1 antibody) + HCQ	Ongoing	I/II	NCT04214418
Advanced	Trametinib (MEK inhibitor) + HCQ	Ongoing	I	NCT03825289
Metastatic	Binimetinib (MEK inhibitor) + HCQ	Ongoing	I	NCT04132505
Advanced	Ulixertinib (ERK inhibitor) + HCQ	Ongoing	I	NCT04145297
Metastatic	LY3214996 ± HCQ (ERK inhibitor)	Ongoing	II	NCT04386057
Advanced pancreatic cancer	mFOLFIRINOX + HCQ + Chlorphenesin Carbamate	Ongoing	I	NCT05083780
Advanced or metastatic	Gem + nabpaclitaxel ± Paricalcitol (Vitamin D receptor agonist) plus HCQ (GnP ± PH)	Ongoing	II	NCT04524702

Gem gemcitabine, GnP gemcitabine + nabpaclitaxel, HCQ hydroxychloroquine, OS overall survival, PFS progression-free survival, RR response rate, R0 resection, complete tumor removal with negative resection margins