Target | Therapeutic | NCT ID | Phase | Indications | Combination therapy | Results reported to date | Ref. | |
ADO | CD38 | Isatuximab | 03367819 | I/II | mCRPC, NSCLC | Cemiplimab | Manageable safety profile ↓ CD38+ immune cells in TME ↑ Activated peripheral T cells | 146 |
A2AAR | Ciforadenant | 02655822 | I | RCC, mCRPC | Atezolizumab | mCRPC: 20% PR for monotherapy and 13% PR for combi therapy | 147 148 | |
AZD4635 | 02740985 | I | Advanced solid tumors, NSCLC, mCRPC, CRC | Abiraterone acetate docetaxel Durvalumab enzalutamide oleclumab | 6% PR for monotherapy 5% CR & 11% PR for combination therapy | 149 | ||
A2AAR & A2BAR | Etrumadenant | 03846310 | I | NSCLC | Carboplatin pembrolizumab Pemetrexed zimberelimab* | 43% PR Did not worsen safety profile | 153 | |
CD73 | Oleclumab | 02503774 | I | Solid tumors | MEDI4736 | ↓Tumorous CD73 expression & ↑CD8 +infiltration in 5/ 9 biopsies | 150 | |
CPI-006 | 03454451 | I | NSCLC, RCC, CRC, TNBC, CC, OC, PC, EC, sarcoma, SCCHN, BC, mCRPC, NHL | Ciforadenant pembrolizumab | Treatment well-tolerated ↓CD73 +B cells, ↑CD73-CD4+T cells, ↓CD8 +T cells one monotherapy patient (9%) saw PR | 151 | ||
KYN | IDO1 | Epacadostat | 02752074 | III | Melanoma | Pembrolizumab | PFS and OS not improved | 162 |
AhR | BAY2416964 | 04069026 | I | Advanced solid tumors | ||||
PGE2 | COX-1 and COX-2 | Aspirin | 02394769 | N/A | CRC | 40%–50% of patients saw ↓ of urinary metabolite of PGE2 below threshold expected to ↓ recurrence | 172 | |
COX-2 | Celecoxib | 00062179 | II | NSCLC | Carboplatin paclitaxel | Normalized PGE2 intratumoral levels Combination therapy: no PD, 17% CR, 48% PR Did not worsen safety profile | 174 | |
EP2 and EP4 | TPST-1495 | 04344795 | I | CRC, NSCLC, SCCHN, UC, EC, | ||||
EP4 | Grapiprant | 03658772 | I | msCRC | Pembrolizumab | |||
NOR/ EPI | β1, β2, and β3 | Propranolol | 02420223 | II | MM | Accelerated engraftment after HCT reduced infection Inhibition of pathways associated with adverse outcomes | 178 | |
β1, β2, β3, and α1 | Carvedilol | 02944201 | II | Prostate cancer |
Each therapeutic candidate is organized by the pathway it pertains to and its target within that pathway. For each therapeutic, an NCT was selected due to novelty and/or intriguing results. We note that several hundred other trials are ongoing that target these pathways, so this table is far from exhaustive.
*No results reported for the Zimberelimab combination treatment arm.
ADO, adenosine; BC, bladder cancer; CC, cervical cancer; CRC, colorectal cancer; EC, endometrial cancer; EPI, epinephrine; GA, gastric adenocarcinoma; GJA, gastroesophageal junction adenocarcinoma; mCRPC, metastatic castrate-resistant prostate carcinoma; NCT, National Clinical Trial; NHL, non-Hodgkin lymphomanon; NOR, norepinephrine; NSCLC, non-small cell lung cancer; OC, ovarian cancer; PC, pancreatic cancer; RCC, renal cell cancer; SCCHN, squamous cell carcinoma of the head and neck; TME, tumor microenvironment; TNBC, triple negative breast cancer; UC, urothelial carcinoma.