Table 2 Ongoing clinical trials using anti-PD-(L)1 combination therapies^a

nivolumab

FOLFIRINOX

resectable / borderline resectable

1

clinically relevant pancreatic fistula in the post-operative period, pCR

I/II

NCT03970252

SBRT

locally advanced

2

incidence of TRAEs, incidence of laboratory abnormalities

I/II

NCT04098432

irreversible electroporation + CpG (toll-like receptor 9 ligand)

metastatic

≥ 2

TRAEs

I

NCT04612530

irreversible electroporation

SX-682 (CXCR1 / 2 inhibitor)

metastatic

≥ 2

MTD

I

NCT04477343

cabiralizumab (CSF1R inhibitor) + gemcitabine

metastatic

2

PFS

II

NCT03697564

APX005M (CD40 agonist) + GA

metastatic

1

number and percentage of subjects with AEs, SAEs, DLTs; OS

Ib/II

NCT03214250

entinostat (class I histone deacetylases inhibitor)

advanced

ORR

II

NCT03250273

TPST-1120 (peroxisome proliferator activated receptor alpha antagonist)

advanced

incidence of DLTs, TEAEs; MTD

I

NCT03829436

autologous dendritic cell vaccine loaded with personalized peptides + gemcitabine, capecitabine

resectable

number of cases for which vaccine is produced, AEs

Ib

NCT04627246

KRAS peptide vaccine + ipilimumab

resected

number of participants experiencing DRTs, fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 16 w

I

NCT04117087

GVAX + SBRT + cyclophosphamide

borderline resectable

no more than 1 month / cycle (28 days) of systemic therapy

CD8 count in the TME

II

NCT03161379

GVAX + cyclophosphamide

resectable

1

median IL-17A expression in vaccine-induced lymphoid aggregates found in surgically resected PC

I/II

NCT02451982

GVAX + urelumab (CD137 agonist) + cyclophosphamide

GVAX + BMS-813160 (CCR2 / CCR5 antagonist) + SBRT

locally advanced

1

number of participants experiencing DRTs, percentage of participants who achieve an immune response (> 80% increase of infiltration of CD8 ⁺ CD137⁺ T cells into the tumor)

I/II

NCT03767582

BMS-813160 + SBRT

ipilimumab + CRS-207 (live, attenuated Listeria monocytogenes-expressing mesothelin) + GVAX + cyclophosphamide

metastatic

ORR

II

NCT03190265

ipilimumab + CRS-207

GRT-C903 (shared neoantigen cancer vaccine prime) + GRT-R904 (shared neoantigen cancer vaccine boost) + ipilimumab

advanced

2

incidence of AEs, SAEs, DLTs; RP2D of GRT-C903 and GRT-R904; ORR in phase 2

I/II

NCT03953235

pembrolizumab

INT230–6 (comprised of 3 agents: cisplatin, vinblastine sulfate, and a cell permeation enhancer)

advanced

no limit

rate and severity of ≥ grade 3 TEAEs

I/II

NCT03058289

PEGPH20

metastatic

2

PFS

II

NCT03634332

efineptakin alfa (NT-I7, long-acting human IL-7)

advanced

2

incidence, nature and severity of AEs, incidence and nature of DLTs, MTD and RP2D of NT-I7; ORR in phase IIa

Ib/IIa

NCT04332653

GB1275 (modulator of CD11b)

metastatic

incidence of DLTs, AEs; maximum plasma concentration, trough plasma concentration, time of maximum observed plasma concentration, terminal phase elimination half-life, area under the plasma concentration-time curve, oral clearance of GB1275; ORR in phase II

I/II

NCT04060342

ENB003 (endothelin B receptor antagonist)

metastatic

≥ 2

incidence of TEAEs, ORR

Ib/IIa

NCT04205227

itacitinib (INCB039110, JAK1 inhibitor)

advanced

frequency, duration, and severity of AEs

Ib

NCT02646748

INCB050465 (PI3K-delta inhibitor)

lenvatinib

advanced

≥ 2

ORR; percentage of participants who experience an AE or discontinue treatment due to an AE

II

NCT03797326

Debio 1143 (a second mitochondrial-derived activator of caspases mimetic designed to promote apoptosis)

Stage III or IV

≥ 2

MTD, RP2D, extension part ORR

I

NCT03871959

defactinib (focal adhesion kinase inhibitor)

advanced

≥ 2

AEs, MTD

I/IIa

NCT02758587

defactinib + gemcitabine

advanced

2

RP2D (determined from MTD)

I

NCT02546531

defactinib + chemotherapy

resectable

1

pCR rate

II

NCT03727880

olaparib (PARP inhibitor) + GAX-CI (gemcitabine, nab-paclitaxel, capecitabine, cisplatin, and irinotecan)

metastatic

1

PFS after 6 m

II

NCT04753879

ipilimumab + anetumab ravtansine (an anti-mesothelin antibody conjugated to the maytansinoid tubulin inhibitor DM4)

advanced

≥ 2

MTD

I

NCT03816358

anetumab ravtansine + gemcitabine

GVAX + IMC-CS4 (LY3022855, anti-CSF1R antibody) + cyclophosphamide

borderline resectable

CD8 T cell density in the primary tumor, number of participants experiencing DRTs

I

NCT03153410

epacadostat + GVAX + cyclophosphamide

metastatic

≥ 2

recommended dose of epacadostat; 6-month survival

II

NCT03006302

epacadostat + CRS-207 (live, attenuated Listeria monocytogenes-expressing mesothelin)

GVAX + cyclophosphamide + SBRT

locally advanced

≥ 2

distant metastasis free survival

II

NCT02648282

p53MVA vaccine

advanced

≥ 2 or refuse standard treatment

tolerability of the combination

I

NCT02432963

mRNA-5671/V941

advanced

DLTs, AEs, discontinuations

I

NCT03948763

pembrolizumab (local delivery via trans-artery or intra-tumor injection)

ipilimumab (local delivery via trans-artery or intra-tumor injection)

advanced

OS, CR rate before or at 6 m

II/III

NCT03755739

spartalizumab

NIS793 (anti-TGF-β antibody)

advanced

incidence of DLTs, AEs, SAEs, dose reductions/interruptions

I

NCT02947165

NIS793 + GA

metastatic

1

incidence of DLTs, incidence and severity of TEAEs and SAEs, dose interruptions / reductions, dose intensity; PFS

II

NCT04390763

canakinumab (ACZ885, anti-IL-1β antibody) + GA

metastatic

1

recommended phase 2 / 3 dose

Ib

NCT04581343

dostarlimab

niraparib (PARP inhibitor)

metastatic

2 or 3

DCR at 12w

II

NCT04493060

sintilimab

mFOLFIRINOX

metastatic

1 or 2

OS

III

NCT03977272

toripalimab

mFOLFIRINOX

borderline resectable / locally advanced

PFS

III

NCT03983057

anlotinib + nab-paclitaxel

locally advanced / metastatic

2

PFS

II

NCT04718701

camrelizumab

GA

metastatic

1

PFS

III

NCT04674956

GA

metastatic

ORR, PFS

II

NCT04498689

plerixafor (AMD3100, CXCR4 antagonist)

metastatic

≥ 2

ORR

II

NCT04177810

zimberelimab

AB680 (CD73 inhibitor) + GA

metastatic

number of participants with TEAEs

I

NCT04104672

unknown PD-1 antibody

radiotherapy

advanced

local control

II

NCT03374293

GA + manganese

locally advanced / metastatic

number of subjects with TRAEs, DCR

I/II

NCT03989310

GA

LYT-200 (galectin-9 inhibitor) + GA

metastatic

incidence of TEAEs and DLTs, PFS, ORR

I/II

NCT04666688

apatinib (VEGFR-2 tyrosine kinase inhibitor) + radiation

advanced

PFS

/

NCT04365049

mutant KRAS G12V-specific TCR transduced autologous T cells + cyclophosphamide, fludarabine

advanced

frequency and severity of TRAEs, ORR

I/II

NCT04146298

durvalumab

danvatirsen (antisense oligonucleotide targeting signal transducer and activator of transcription 3)

refractory / stage II / stage III / stage IV

incidence of AEs, SAEs; physiological parameters; incidence of TEAEs and deaths; PD-L1 expression; phosphorylated or total STAT3 expression levels; characterization of immune infiltrates; quantification and characterization of CD8 staining pattern; PD-L1 protein levels in the membrane of circulating tumor cells; physical examinations

II

NCT02983578

olaparib (PARP inhibitor)

advanced

changes in genomic and immune biomarkers

II

NCT03851614

cediranib (inhibitor of VEGFR tyrosine kinases)

tremelimumab + SBRT

advanced

≥ 2

number of AEs with grade 1–5

I/II

NCT02311361

SBRT

CV301 (poxviral-based vaccine) + capecitabine

metastatic

2

RP2D of durvalumab, 8.5-month PFS rate, 4-month PFS rate

I/II

NCT03376659

atezolizumab

BDB001 (Toll-like receptor agonist) + radiotherapy

metastatic

DCR within 24 w

II

NCT03915678

KY1044 (anti-ICOS antibody)

advanced

incidence and severity of AEs and SAEs; number of dose interruptions, reductions and dose intensity; ORR

I/II

NCT03829501

personalized neoantigen tumor vaccines + mFOLFIRINOX

resectable

1

DRT

I

NCT04161755

LOAd703 (oncolytic adenovirus encoding TMZ-CD40L and 4-1BBL) + GA

advanced

number of patients with DLTs

I/IIa

NCT02705196

avelumab

binimetinib (MEK inhibitor) + talazoparib (PARP inhibitor)

locally advanced / metastatic

2 or 3

DLT, confirmed objective response

Ib/II

NCT03637491

binimetinib

ETBX-011 (vaccine inducing CEA-specific cytotoxic T-cell activity) + GI-4000 (vaccine expressing mutant Ras proteins) + haNK + ALT-803 (IL-15 superagonist) + bevacizumab + aldoxorubicin HCl, capecitabine, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ehtyl esters, oxaliplatin + SBRT

advanced

≥ 2

incidence of TEAEs and SAEs, ORR

Ib/II

NCT03387098^b

ETBX-011 + ETBX-021 (HER2) + ETBX-051 (Brachyury) + ETBX-061 (MUC1) + GI-4000 + GI-6207 (CEA yeast) + GI-6301 (Brachyury yeast) + haNK + ALT-803 + bevacizumab + aldoxorubicin HCl, capecitabine, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, oxaliplatin + SBRT

advanced

≥ 2

incidence of TEAEs and TESAEs, ORR

Ib/II

NCT03586869

LY3300054 (anti-PD-L1 antibody)

merestinib (multikinase inhibitor)

locally advanced / metastatic

1

number of participants with LY3300054 DLTs

I

NCT02791334

SHR-1701 (PD-L1/TGF-β bsAb)

GA

advanced

1

RP2D, ORR

Ib/II

NCT04624217

PD-L1/CTLA-4 bsAb

/

locally advanced / metastatic

2

ORR

I/II

NCT04324307

GA

1

FOLFIRINOX

1

PD-L1 targeting haNK

N-803 (IL-15 superagonist) + SBRT + cyclophosphamide, gemcitabine, nab-paclitaxel, aldoxorubicin HCl

locally advanced / metastatic

≥ 2

PFS

II

NCT04390399