Skip to main content

Table 2 Prospective clinical trials supporting combination regimens incorporating systemic therapies and immune checkpoint inhibitors in pancreatic cancer

From: Combination systemic therapies with immune checkpoint inhibitors in pancreatic cancer: overcoming resistance to single-agent checkpoint blockade

Study design, setting Treatment arms Outcomes Refs.
Phase Ib, previously gemcitabine-treated Ipilimumab IV 10 mg/kg (n = 15) vs. ipilimumab + GVAX vaccine intradermal injection ×4 (n = 15) on weeks 1, 4, 7, and 10 → maintenance every 12 weeks if response or SD Median OS 3.6 mos (95% CI 2.5–9.2) vs. 5.7 mos (95% CI 4.3–14.7, HR 0.51, 95% CI 0.23–1.08, p = 0.072)
SD 2/15 (13.3%) vs. SD 3/15 (20%)
[45]
Phase Ib, 1st-line Tremelimumab IV 6–15 mg/kg on D1 every 84-day cycles + G 1000 mg/m2 weekly ×3 weeks every 4-week cycles (n = 34) Median OS 7.4 mos (95% CI 5.8–9.4)
PR 2/19 (10.5%) at MTD of 15 mg/kg trememlimumab
[48]
Phase Ib, gemcitabine-naïve MTD: Ipilimumab IV 3 mg/kg every 3 weeks ×4 doses + G 1000 mg/m2 weekly ×3 weeks every 4-week cycles (n = 16) → maintenance ipilimumab every 12 weeks and G weekly ×3 weeks every 4-week cycles PR 2/16 (12.5%)
Median PFS 2.5 mos (95% CI 0.8–4.8)
Median OS 8.5 mos (95% CI 2.2–10.3)
[51]
Pilot study, NR Monocyte derived dendritic cell vaccine (dose NR) + nivolumab IV 1–2 mg/kg 1 day before vaccine (n = 7) 2 PRs with OS after onset of therapy of 13 and 5 mos [47]
Phase Ib, treatment-refractory BGB-A317 (PD-1 inhibitor) IV 2 mg/kg or 200 mg every 3 weeks + BGB-290 (PARP 1/2 inhibitor) oral 20–60 mg twice daily (n = 38, advanced solid tumors) 7 PRs (1 pancreatic cancer) and 6 SD for > 6 mos (2 pts with pancreatic cancer who received BGB-A317 + BGB-290 for 189 and 281 days)
Most common treatment-related AE was fatigue (10.5%)
Immune-related AEs: Grade 3 hypophysitis (n = 1), grade 3–4 autoimmune hepatitis (n = 2), and grade 2 transaminitis (n = 1)
[55]
Phase Ib, 1st- and 2nd-line Treatment-naïve: Pembrolizumab IV 2 mg/kg D1 + G 1000 mg/m2 + N 125 mg/m2 D1 and 8 every 21-day cycles (n = 11)
Pretreated: Pembrolizumab + G 800 mg/m2 + N 100 mg/m2 D1 and 8 every 21-day cycles (n = 4)
Treatment-naïve: PR 3/11 (27.2%), median PFS 9.1 mos (95% CI 4.9–15.3), median OS 15 mos (95% CI 6.8–22.6)
Pretreated: SD 2/4 (50%, closed due to futility)
[50]
Phase I, 1st- and 2nd-line Arm A: Nivolumab IV 3 mg/kg D1 and 15 + N 125 mg/m2 D1, 8, and 15 every 28-day cycles (previously treated with 1 line of chemotherapy, n = 11)
Arm B: Same as arm A with G 1000 mg/m2 weekly ×3 weeks every 4-week cycles (treatment-naïve, n = 6)
Arm A: PR 2/9 (22.2%)
Arm B: PR 3/6 (50%)
[52]
Phase I, neoadjuvant Arm A: Pembrolizumab IV 200 mg D1, 22, and 43 + X 825 mg/m2 twice daily (on days of RT only) + 50.4 Gy ×28 fractions ×28 days (n = 14)
Arm B: X + RT only (n = 8)
Arm A: 10/14 resection (71.4%) with grade 3 AEs of diarrhea (n = 2), lymphopenia (n = 4), and elevated alkaline phosphatase (n = 1)
Arm B: 4/14 resection (28.6%) with 1 grade 3 AE of lymphopenia
[53]
Phase I, treatment-refractory Epacadostat oral 25 mg or 100 mg twice daily ± pembrolizumab IV 200 mg every 3 weeks (n = 15, 1 pancreatic cancer) PR in pancreatic cancer pt who remains on therapy at 21 weeks [56]
Phase I, treatment-refractory M7824 (avelumab fused to the extracellular domain of TGFβ receptor II) IV 1, 3, 10, or 20 mg/kg every 2 weeks (n = 5) MTD not reached with 1 each (n = 19) of grade ≥ 3 anemia, colitis, gastroparesis, hypokalemia, elevated lipase, and skin infection
PR 1/5 (20%)
SD 3/5 (60%)
[58]
Phase II, 2nd-line Durvalumab IV 1.5 g IV every 4 weeks (n = 33) or durvalumab IV 1.5 g + tremelimumab IV 75 mg every 4 weeks ×4 doses → durvalumab IV 1.5 g every 4 weeks up to 12 mos (n = 32) Monotherapy: 2 unconfirmed PRs (6.1%), DCR 6.1%, median PFS 1.5 mos, median OS 3.6 mos
Combination: 1 PR (3.1%) > 12 mos, DCR 9.4%, median PFS 1.5 mos, and median OS 3.1 mos
[57]
Phase II, 1st-line G 1000 mg/m2 D1, 8, and 15 + N 125 mg/m2 D1, 8, and 15 + durvalumab IV 1500 mg D1 + tremelimumab IV 75 mg D1 every 28-day cycles (n = 11) PR 8/11 (73%, median duration 7.4 mos)
DCR 100%
Median PFS 7.9 mos (95% CI 3.5–9.2)
[54]
  1. IV intravenous, GVAX allogeneic pancreatic tumor cells transfected with granulocyte–macrophage colony-stimulating factor (GM-CSF) gene, SD stable disease, OS overall survival, CI confidence interval, HR hazard ratio, PR partial response, D day, MTD maximum-tolerated dose, PFS progression-free survival, NR not reported, PD-1 programmed cell death protein 1 receptor, PARP poly (ADP-ribose) polymerase, G gemcitabine, N nab-paclitaxel, X capecitabine, RT radiation therapy, Gy gray, AE adverse event, TGFβ transforming growth factor beta, DCR disease control rate