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

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]