Table 1 Published clinical trials using anti-PD-(L)1 combination therapy
From: Combination therapy for pancreatic cancer: anti-PD-(L)1-based strategy
Publication year | Study phase | PC stage | Treatment line | Treatment regimens | Number of PC pts | Efficacy |
|---|---|---|---|---|---|---|
Combination with chemotherapy | ||||||
 2017 | Ib/II | metastatic | 1 / 2 | pembrolizumab + gemcitabine, nab-paclitaxel | 17 | (Among the 11 chemotherapy naïve pts.) DCR 100%; mPFS 9.1 m, mOS 15.0 m |
 2020 | I | locally advanced / metastatic | 1 / 2 | nivolumab + gemcitabine, nab-paclitaxel | 50 | (Among the 50 chemotherapy naïve pts.) ORR 18%, DCR 64%; mPFS 5.5 m, mOS 9.9 m |
 2020 | / (case) | metastatic | 1 | toripalimab + gemcitabine, nab-paclitaxel | 1 | PR for at least 8 cycles |
Combination with radiotherapy | ||||||
 2019 | I/II | borderline resectable / locally advanced | 2 | durvalumab + stereotactic ablative radiotherapy | 15 | 6 underwent R0 resection |
 2018 | I | metastatic | ≥ 2 | pembrolizumab + hypofractionated radiotherapy | 4 | all PD |
 2017 | Ib/II (randomized controlled study) | resectable / borderline resectable | 1 | pembrolizumab + radiation + capecitabine | 22 (14 pts. in the triple therapy arm) | 71% underwent surgery (compared to 50% in the arm only receiving capecitabine and radiation) |
Combination with molecularly targeted therapy | ||||||
 2019 | II | metastatic | 1 | nivolumab + gemcitabine, nab-paclitaxel, cisplatin + paricalcitol | 24 | 19 PR, 2 SD and 2 PD; mPFS 8.17 m, mOS 15.3 m |
 2018 | I | locally advanced / metastatic |  | M7824 (a bifunctional fusion protein of anti-PD-L1 antibody fused to the extracellular domain of TGF-β receptor II) | 5 | 1 durable PR (with dMMR), 1 prolonged SD |
 2019 | Ib | metastatic |  | durvalumab + galunisertib (TGF-β receptor I kinase inhibitor) | 32 | 1 PR, 7 SD; mPFS 1.9 m |
 2017 | I | advanced | ≥ 2 | nivolumab + cabiralizumab (anti-CSF1R antibody) | 31 | 3 PR (293, 275+, and 168+ days on study), 1 prolonged SD (182 d); 6-month DCR 13%, ORR 10% |
 2018 | Ib/II | advanced |  | spartalizumab (anti-PD-1 antibody) + lacnotuzumab (anti-CSF1R antibody) | 30 | 1 PR (on study for 346 d), 2 durable SD (on study for 328 d and 319 d) |
 2021 | Ib | metastatic | 1 | nivolumab + APX005M (sotigalimab, CD40 agonist) + gemcitabine, nab-paclitaxel | 12 | 8 PR, 3 SD; mPFS 10.8 m (0.1 mg/kg APX005M) / 12.4 m (0.3 mg/kg APX005M) |
 2020 | I/II | metastatic | 3 mean lines of prior treatment | pembrolizumab + NOX-A12 (CXCL12 inhibitor) | 9 | (among 11 colorectal cancer pts. and 9 PC pts.) 25% SD; mPFS 1.87 m, 6-month OS 42%, 12-month OS 22% |
 2019 | IIb | metastatic | 2 mean lines of prior treatment | pembrolizumab + BL-8040 (CXCR4 antagonist) | 15 | 1 PR, 2 SD, DCR 21.4%; mOS 7 m |
 2020 | IIa | metastatic | ≥ 2 | pembrolizumab + BL-8040 (CXCR4 antagonist) | 37 | (Among the 29 chemotherapy-resistant evaluable pts.) 1 PR, 9 SD, DCR 34.5%; mOS 3.3 m |
2 | pembrolizumab + BL-8040 (CXCR4 antagonist) + liposomal irinotecan, fluorouracil, leucovorin | 22 | ORR 32%, DCR 77%; median duration of response 7.8 m | |||
 2018 | I | ? |  | pembrolizumab + defactinib (FAK inhibitor) + gemcitabine | 8 | 1 PR; median time on treatment 127 d |
 2020 | II (randomized controlled study) | locally advanced / metastatic | ≥ 2 | pembrolizumab + acalabrutinib (BTK inhibitor) | 77 (40 pts. in the combination therapy arm) | ORR 7.9%, DCR 21.1% |
 2017 | Ib | advanced |  | BGB-A317 (anti-PD-1 antibody) + BGB-290 (PARP 1 / 2 inhibitor) | ? (38 pts. in all, including ovarian, breast, prostate, pancreatic cancers, etc.) | (among PC pts.) 1 PR, 2 SD (received the combination therapy for 189 d and 281 d) |
 2019 | Ib | advanced |  | dostarlimab (PD-1 inhibitor) + niraparib (PARP inhibitor) + bevacizumab | ? | 1 SD in a PC pt |
Combination with immunotherapy | ||||||
 2020 | / (cases) | relapsed / refractory | complicated | nivolumab + ipilimumab | 5 | (among 3 evaluable pts.) 1 CR (with BRCA1), 1 PR (with RAD51C) |
 2019 | II | metastatic | ≥ 2 | nivolumab + ipilimumab + radiation | 25 | ORR 13%, DCR 20% |
 2018 | II (randomized controlled study) | metastatic | ≥ 2 | durvalumab + tremelimumab | 64 (32 pts. in the combination therapy arm) | DCR 9.4%; mPFS 1.5 m, mOS 3.1 m |
 2018 | II | metastatic | 1 | durvalumab + tremelimumab + gemcitabine, nab-paclitaxel | 11 | PR 73%, DCR 100%; mPFS 7.9 m, 6-month survival 80% |
 2018 | I | advanced | ≥ 2 | pembrolizumab + epacadostat (IDO1 inhibitor) | 1 | PR (on treatment at 21 w) |
 2019 | I | advanced |  | atezolizumab + navoximod (IDO1 inhibitor) | 1 | PR |
 2015 | / | metastatic | 2 | antigen-primed MoDCs modified by PD-L1 blockade | 10 | 5 pts. (didn’t respond to MoDC alone) achieved secondary stabilization (4 m to 8 m) by using MoDCs modified by PD-L1 blockade |
 2016 | / | metastatic |  | nivolumab + antigen-primed MoDCs | 7 | 2 PR |
 2019 | Ib | advanced | 2 | pembrolizumab + pelareorep (oncolytic reovirus) + chemotherapy | 11 | (among 10 efficacy-evaluable pts.) 1 PR for 17.4 m, 2 SD lasting 9 m and 4 m |