Table 2 –
Ongoing clinical trials targeting adenosine metabolism in patients with malignancies
| Target | Drug +/− combination therapy |
Company | Cancer type | ClinicalTrials.gov identifier | Study phase |
|---|---|---|---|---|---|
| NTPDase1/CD39 | Human anti-CD39 Ab (TTX-030) +/− chemotherapy (docetaxel, gemcitabine, nab-paclitaxel), or anti-PD-1 mAb (pembrolizumab) |
Tizona Therapeutics | Solid tumors, lymphoma | NCT03884556 | I |
| eN/CD73 | anti-CD73 mAb (MEDI9447/oleclumab) +/− EGFR tyrosine kinase inhibitor (osimertinib), or A2R antagonist (AZD4635) |
MedImmune | NSCL carcinoma | NCT03381274 | I/II |
| eN/CD73 | anti-CD73 mAb (MEDI9447/oleclumab) +/− anti-PD-L1 mAbs (durvalumab, tremelilumab), or anti-OX40/CD134 mAb (MEDI0562/tavolimab) |
Nordic Society for Gynaecologic Oncology | Ovarian cancer | NCT03267589 | II |
| eN/CD73 | anti-CD73 mAb (MEDI9447/oleclumab) +/− anti-PD-L1 mAb (MEDI4736/durvalumab) |
MedImmune | Solid tumors | NCT02503774 | I |
| eN/CD73 | anti-CD73 mAb (MEDI9447/oleclumab) +/− chemotherapy (paclitaxel plus carboplatin), anti-PD-L1 mAbs (durvalumab) |
Jules Bordet Institute/AstraZeneca | TNBC | NCT03616886 (SYNERGY) | I/II |
| eN/CD73 | anti-CD73 mAb (BMS-986179) +/− anti-PD-1 mAb (nivolumab), or rHuPH20 |
Bristol-Myers Squibb | Advanced solid tumors | NCT02754141 | I/II |
| eN/CD73 | anti-CD73 mAb (NZV930/SRF373) +/− anti-PD-1 mAb (PDR001), or A2R antagonist (NIR178) |
Novartis Pharmaceuticals | Advanced solid tumors | NCT03549000 | I |
| eN/CD73 | anti-CD73 mAb (CPI-006) +/− anti-PD-1 mAb (pembrolizumab), or A2R antagonist (CPI-444) |
Corvus Pharmaceuticals | Advanced solid tumors, Non-Hodgkin lymphoma | NCT03454451 | I |
| eN/CD73 | anti-CD73 mAb (TJ004309/TJD5) +/− anti-PD-L1 mAb (atezolizumab) |
Tracon Pharmaceuticals | Solid tumors, metastatic cancer | NCT03835949 | I |
| eN/CD73 | small-molecule eN/CD73 inhibitor (AB680) | Arcus Biosciences | Healthy volunteers | NCT03677973 | I |
| eN/CD73 | small-molecule eN/CD73 inhibitor (AB680) +/− anti-PD-1 Ab (AB122) |
Arcus Biosciences | Advanced pancreatic cancer | NCT04104672 | I |
| ADA | ADA inhibitor pentostatin +/− chemotherapy (bendamustine), or anti-CD20 mAb (rituximab) |
National Cancer Institute | Hairy Cell Leukemia | NCT01059786 | II |
| CD38 | anti-CD38 mAb (Isatuximab/SAR650984) +/− anti-PD-1 mAb (cemiplimab) |
Sanofi | Lymphoma Prostate and NSCL cancers MM |
NCT03769181 NCT03367819 NCT03733717 |
I/II I/II I |
| CD38 | anti-CD38 mAb (Isatuximab) +/− standard immuno- and chemotherapy |
Sanofi | ALL, AML | NCT03769181 | II |
| CD38 | anti-CD38 mAb (Isatuximab) +/− immunotherapy (dexamethasone, lenalidomide), or proteasome inhibitor (bortezomib) |
University of Heidelberg Medical Center | MM | NCT03617731 | III |
| CD38 | anti-CD38 mAb (Isatuximab) monotherapy |
M.D. Anderson Cancer Center | Smoldering MM | NCT02960555 | II |
| CD38 | Human anti-CD38 Ab (MOR202/MOR03087) +/− immunotherapy (dexamethasone, pomalidomide, lenalidomide) |
MorphoSys AG | Relapsed or refractory MM | NCT01421186 | I/II |
| CD38 | anti-CD38 mAb (TAK079) +/− immunotherapy (dexamethasone, pomalidomide) |
Takeda - Millennium Pharmaceuticals | Relapsed or refractory MM | NCT03439280 | I/II |
| CD38 | Human anti-CD38 Ab (daratumumab) monotherapy |
M.D. Anderson Cancer Center | Bladder and kidney cancers Myeloid leukemia Plasma cell myeloma |
NCT03473730 NCT03067571 NCT03622775 |
I II II |
| CD38 | Human anti-CD38 Ab (daratumumab) monotherapy |
Dana-Farber Cancer Institute | Smoldering MM | NCT03236428 | II |
| CD38 | Human anti-CD38 Ab (daratumumab) +/−FMS tyrosine kinase inhibitor (JNJ-40346527) |
M.D. Anderson Cancer Center | Prostate cancer | NCT03177460 | I |
| CD38 | Human anti-CD38 Ab (daratumumab) +/− immunotherapy (ibrutinib) |
French Innovative Leukemia Organisation | Relapsed or refractory CLL | NCT03734198 | II |
| CD38 | CD38/CD3 bispecific antibody (GBR 1342) | Glenmark Pharmaceuticals | MM | NCT03309111 | I |
| CD38 | anti-CD38 mAb (SAR650984) +/− proteasome inhibitor (carfilzomib) |
University of California, San Francisco | MM | NCT02332850 | I |
| CD38 | Daratumumab labeled with zirconium-89 through deferoxamine (89Zr-DFO-daratumumab) | Memorial Sloan Kettering Cancer Center | PET imaging of MM | NCT03665155 | I/II |
| CD38 | Autologous CD38-A2 CAR2-expressing T lymphocytes | Sorrento Therapeutics | Relapsed or refractory MM | NCT03464916 | I |
Abbreviations: ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CLL, chronic lymphocytic leukemia; EGFR, epidermal growth factor receptor; MM, multiple myeloma; NSCL cancer, non-small cell lung cancer; rHuPH20, novel drug delivery enzyme, fully human recombinant DNA-derived hyaluronidase; PET, positron emission tomography. Note, multiple clinical trials have been initiated recently for evaluating the therapeutic potential, effective dosage and possible side effects of daratumumab, isatuximab and other anti-CD38 antibodies in cancer patients, with over 50 recruiting trials being listed on ClinicalTrials.gov. Due to the lack of space, only a selection of these ongoing CD38-targeting trials have been listed here.