Table 2.

Selected ongoing clinical trials evaluating immunotherapeutic approaches in PDAC

Identifier	Trial and strategy	Mechanism of action	Design of clinical trial	Primary and secondary end points
NCT00727441	Phase II study of GVAX vaccine±cyclophosphamide in resectable PDAC	Induction of effector immune cells and inhibition of T regulatory cells via whole cell cancer vaccine	Arm A: GVAX day 1 and 6–10 weeks after surgery on day 15. Arm B: CTX day 0 and GVAX day 1 and 6–10 weeks after surgery (day 15). Arm C: GVAX day 1 and 6–10 weeks after Sx, CTX days 1–7 and days 1–7 after surgery	PE: safety, feasibility, and immune response SE: OS and PFS
NCT02451982	Phase 1/2 study of neoadjuvant/adjuvant GVAX vaccine±nivolumab (anti PD-1)	Induction of effector immune cells with whole cell cancer vaccine±removal of negative regulatory signals	Arm A: CTX day 0, GVAX day 1 and 6–10 days after Sx (4 course), Sx day 15 and Adjuvant Arm B: CTX day 0, GVAX day 1 and 6–10 weeks after Sx (4 course), Sx day 15 and nivolumab day 0 and 6–10 weeks after Sx	PE: median IL17A expression in vaccine-induced lymphoid aggregates SE: OS and DFS
NCT01896869	Phase II study of Ipilimumab (anti-CTLA4) and GVAX vaccine in metastatic PDAC	Induction of effector immune cells with whole cell cancer vaccine±removal of negative regulatory signals	Arm A: FOLFIRNOX followed by Ipilimumab+GVAX; Ipilimumab and GVAX will be administered every 3 weeks for 4 doses, then every 8 weeks. Arm B: FOLFIRINOX continuous	PE: OS SE: adverse effects, PFS, objective response, immune-related PFS, CA19-9
NCT02548169	Phase I study of antigen-loaded Dendritic cell in combination with chemotherapy	Induction of effector immune cells	Arm A: DC Vaccine+standard of care chemotherapy in resectable or locally advance disease Arm B: DC Vaccine+standard of care chemotherapy in metastatic PDAC patients	PE: safety and feasibility SE: OS, PFS
NCT02243371	Phase II study of GVAX vaccine and CRS-207±nivolumab in metastatic PDAC patients	Induction of effector immune cells with whole cell cancer vaccine±removal of negative regulatory signals	Arm A: CRS day 2 (1 x 109 CFU) of cycles 3–6, GVAX day 1 of cycles 1 and 2 and nivolumab day 1 of cycles 1–6. Arm B: CRS day 2 (1×109 CFU) of cycles 3–6, GVAX day 1 cycles of 1 and 2	PE: OS SE: systemic toxicities, TTP, immune-related PFS, response rate (RECIST), CA19-9
NCT01473940	Phase I study of ipilimumab with gemcitabine in advanced stage PDAC	Induction of effector immune cells by removing negative regulatory signals	Single arm induction: ipilimumab weeks 1, 4, 7, and 10; gemcitabine weeks 1–7 and 9–11. Maintenance: ipilimumab every 12 weeks and gemcitabine once weekly for 3 weeks	PE: safety and adverse effects SE: OS, PFS, RR, and T-cell response
NCT02558894	Phase II study of durvalumab (anti-PD-L1)±tremelimumab (anti-CTLA4) in metastatic PDAC	Induction of effector immune cells by removing negative regulatory signals with immune check point inhibitors	Arm A: durvalumab single agent i.v. infusion. Arm B: durvalumab in combination with Tremelimumab i.v. infusion	PE: objective RR. SE: duration of response, disease control rate, progression free survival, pharmacokinetics
NCT02268825	Phase I, IIA study of pembrolizumab (anti-PD-1) in combination with mFOLFOX in advanced stage GI cancers	Induction of effector immune cells by removing negative regulatory signals with immune check point inhibitor	Single arm: pembrolizumab day 1 of each cycle of FOLFOX (total 14 days)	PE: safety and tolerability in combination with mFOLFOX
NCT02309177	Phase I study of Nivolumab (anti-PD-1) with Nab-paclitaxel±gemcitabine in advanced stage PDAC	Induction of effector immune cells by removing negative regulatory signals with immune check point inhibitor	Arm A: nivolumab days 1 and 15 of each 28-day cycle. Nab-paclitaxel days 1, 8, and 15. Arm B: nivolumab days 1 and 15 of each 28-day cycle. Nab-paclitaxel days 1, 8, and 15, and gemcitabine days 1, 8, and 15	PE: dose limiting toxicities, safety. SE: OS, PFS, disease control rate, duration of response
NCT02303990 (RADVAX trial)	Phase I study of Pembrolizumab in combination with hypofractionated radiation therapy	Induction of effector immune cells by immune check point inhibitor and sensitization of T cells by radiotherapy	Single arm: pembrolizumab along with radiation treatment	PE: safety and dose limiting toxicities
NCT02077881	Phase 1/2 study of Indoximod (IDO inhibitor) in combination with gemcitabine and nab-paclitaxel in metastatic PDAC	Induction of effector immune cells by modifying tumor metabolism	Single arm: indoximod twice daily×28 days each cycle. Gemcitabine, Nab-paclitaxel days 1, 8, and 15 28 days	PE: dose determination, OS (in phase II) SE: RR, biomarker response, and time to progression of disease

Sx, surgery; CTX, cyclophosphamide; PE, primary end point; SE, secondary end points; OS, overall survival; PFS, progression-free survival; RR, response rate; DFS, disease-free survival; TTP, time-to-progression.