Table 3.
Ongoing trials evaluating T-DXd in combination with ICIs and TKIs.
| Study | Drugs | Phase | No. of pts. | Population | Primary Endpoints |
|---|---|---|---|---|---|
| NCT05480384 (BrUOG 413) [102] | T-DXd + nivolumab | II | 25 | Adjuvant treatment after trimodality treatment in HER2+ esophagus and GEJ | Safety |
| NCT04539938 (HER2CLIMB-04) [103] | T-DXd + tucatinib | II | 70 | HER2+ MBC after progression on taxane + T | ORR |
| NCT05633979 [104] | T-DXd + valemetostat | Ib | 37 | Low-HER2 /ultra-low/null MBC | Safety, MTD, ORR, RDE |
| NCT05795101 (TRUDI) [105] | T-DXd + durvalumab | II | 63 | First-line HER2+/low inflammatory breast cancer | pCR |
| NCT05372614 [106] | T-DXd + neratinib | I | 18 | Metastatic HER2-altered cancers | DLTs TEAEs |
| NCT04704661 (DASH) [107] | T-DXd + AZD6738 | I | 15 | Advanced solid tumors with HER2 expression | Safety, RP2D |
| NCT04538742 (DB-07) [108] | T-DXd + durvalumab or pertuzumab or paclitaxel or tucatinib | I/II | 245 | First-line HER2+ advanced and/or MBC | AEs, SAEs |
| NCT04042701 [109] | T-DXd + pembrolizumab | I | 115 | MBC or NSCLC | DLTs, ORR |
| NCT04686305 (DESTINY-Lung03) [110] | T-DXd + durvalumab + pemetrexed or platinum | Ib | 136 | First-line HER2+ advanced or metastatic NSCLC | AEs SAEs |
| NCT04379596 (DESTINY-Gastric03) [111] | T-DXd alone or + durvalumab or pembro and CT | Ib/II | 351 | HER2+ previously treated or untreated gastric and GEJ or esophageal cancer patients | AEs, SAEs, ORR |
| NCT04585958 [112] | T-DXd + olaparib | I | 55 | Metastatic HER2-expressing cancers | MTD, RP2D, AEs |
| NCT03334617 (HUDSON) [113] | Cohort T-DXd + durvalumab | II | 570 | NSCLC progressed on anti-PD-1/PD-L1 containing therapy | ORR |
RDE: recommended dose for expansion; T-DXd: trastuzumab deruxtecan; MBC: metastatic breast cancer; NSCLC: non-small-cell lung cancer; DLTs: dose-limiting toxicities; ORR: overall response rate; AEs: adverse events; SAEs: serious adverse events; MTD: maximum tolerated dose; RP2D: recommended phase 2 dose; GEJ: gastro-esophageal junction; PD-1: programmed death-1; PD-L1: programmed death ligand-1; TEAEs: treatment-emergent adverse events; pCR: pathologic complete response; CT: chemotherapy; pts: patients; nb: number.