Table 3 Ongoing trials for EGFR-mutated NSCLC patients with osimertinib resistance
NCT number | Phase | Pts | Treatment arm(s) | Primary endpoint(s) |
|---|---|---|---|---|
Targeted therapy | ||||
 NCT04862780 (SYMPHONY) | 1/2 | 120 | BLU-945 (EGFR inhibitor) | MTD, RP2D, AEs, ORR |
 NCT03940703 (INSIGHT 2) | 2 | 120 | Osimertinib + tepotinib (MET inhibitor) | ORR |
NCT04816214 | 3 | 245 | Osimertinib + capmatinib (MET inhibitor); Platinum + pemetrexed | DLT, PFS |
 NCT03778229 (SAVANNAH) | 2 | 259 | Osimertinib + savolitinib (MET inhibitor) | ORR |
 NCT05015608 (SACHI) | 3 | 250 | Osimertinib + savolitinib; Pemetrexed + platinum | PFS |
 NCT03255083 | 1 | 13 | Osimertinib + DS-1205c (AXL inhibitor) | Number of participants with DLT |
 NCT02503722 | 1 | 36 | Osimertinib + sapanisertib (mTOR inhibitor) | MTD and DLT |
 NCT03532698 | / | 100 | Osimertinib and aspirin; Osimertinib | ORR |
 NCT04001777 | 1 | 60 | Osimertinib + palcitoclax (Bcl-2 inhibitor) | MTD, RP2D |
 NCT02520778 | 1 | 50 | Osimertinib and navitoclax (Bcl-2 inhibitor) | Incidence of toxicity |
 NCT02917993 | 1/2 | 59 | Osimertinib + itacitinib (JAK1 inhibitor) | AEs, DLT and ORR |
 NCT03455829 | 1/2 | 30 | Osimertinib + lerociclib (CDK4/6 inhibitor) | DLT, RP2D, AEs and PFS |
 NCT04545710 | 2 | 18 | Osimertinib + abemaciclib (CDK4/6 inhibitor) | PFS |
 NCT03944772 (ORCHARD) | 2 | 150 | Osimertinib + gefitinib; Osimertinib + necitumumab (anti-EGFR mAb); Osimertinib + alectinib (ALK inhibitor); Osimertinib + selpercatinib (RET inhibitor); Osimertinib + savolitinib | ORR |
 NCT02143466 (TATTON) | 1 | 344 | Osimertinib + selumetinib (MEK inhibitor); Osimertinib + savolitinib; Osimertinib + durvalumab (PD-L1 mAb) | Number of participants with AEs |
Chemotherapy | ||||
 NCT04765059 (COMPEL) | 3 | 204 | Osimertinib + chemotherapy; Placebo + chemotherapy | PFS |
 NCT04769388 (FLAME) | 2 | 150 | Osimertinib monotherapy; Osimertinib + chemotherapy | PFS |
 NCT04035486 (FLAURA2) | 3 | 587 | Osimertinib; Osimertinib +  pemetrexed/cisplatin; Osimertinib + pemetrexed/carboplatin | -PFS |
 NCT04695925 (TOP) | 3 | 291 | Osimertinib; Osimertinib + pemetrexed/carboplatin | PFS |
 NCT03567642 | 1 | 20 | Osimertinib + platinum/etoposide | MTD |
Immunotherapy | ||||
 NCT04099836 | 2 | 39 | Atezolizumab + bevacizumab | ORR |
 NCT02496663 | 1 | 100 | Osimertinib + necitumumab (anti-EGFR antibody) | MTD and incidence of toxicity |
 NCT04285671 | 1/2 | 26 | Osimertinib + necitumumab + trastuzumab | RP2D, AEs, ORR |
 NCT03133546 (BOOSTER) | 2 | 155 | Osimertinib + bevacizumab; Osimertinib | PFS |
 NCT04181060 | 3 | 300 | Osimertinib + bevacizumab; Osimertinib | PFS |
 NCT03909334 | 2 | 150 | Osimertinib + ramucirumab; Osimertinib | PFS |
 NCT03784599 (TRAEMOS) | 2 | 58 | Osimertinib + trastuzumab emtansine (HER2 ADC) | ORR |
 NCT03505710 (DESTINY-Lung01) | 2 | 181 | Trastuzumab deruxtecan (HER2 ADC) | ORR |
 NCT04644237 (DESTINY-Lung02) | 2 | 150 | Trastuzumab deruxtecan | ORR |
 NCT04619004 (HERTHENA-Lung01) | 2 | 420 | Patritumab deruxtecan (HER3 ADC) | ORR |
 NCT05338970 (HERTHENA-Lung02) | 3 | 560 | Patritumab deruxtecan; Platinum + pemetrexed | PFS |
 NCT04676477 | 1 | 252 | Osimertinib + patritumab deruxtecan | DLT, AEs, ORR |
 NCT03539536 | 2 | 270 | Telisotuzumab vedotin (ABBV-399, a MET ADC) | ORR, AEs |
 NCT02099058 | 1 | 260 | ABBV-399; ABBV-399 + nivolumab; ABBV-399 + erlotinib; ABBV-399 + osimertinib | AEs, RP2D |
 NCT04484142 (TROPION-Lung05) | 2 | 137 | Datopotamab deruxtecan (TROP2 ADC) | ORR |
 NCT04526691 (TROPION-Lung02) | 1 | 120 | Datopotamab deruxtecan + pembrolizumab; Datopotamab deruxtecan + pembrolizumab + platinum | DLTs |
NCT04487080 (MARIPOSA) | 3 | 1074 | Amivantamab + lazertinib; Osimertinib; Lazertinib | -PFS |
Chemoimmunotherapy | ||||
 NCT03515837 (KEYNOTE789) | 3 | 492 | Platinum + pemetrexed; Platinum + pemetrexed + pembrolizumab | PFS and OS |
 NCT02864251 (CheckMate722) | 3 | 274 | Platinum + pemetrexed; Platinum + pemetrexed + nivolumab; Ipilimumab + nivolumab | PFS |
 NCT03786692 | 2 | 117 | Atezolizumab + bevacizumab + carboplatin + pemetrexed; Bevacizumab + carboplatin + pemetrexed | PFS |
 NCT04147351 | 2 | 22 | Atezolizumab + bevacizumab + platinum + pemetrexed | ORR |
 NCT03991403 | 3 | 228 | Atezolizumab + bevacizumab + carboplatin + paclitaxel; Platinum + pemetrexed | PFS |
 NCT02609776 (CHRYSALIS) | 1 | 780 | Amivantamab (EGFR/MET BsAb); Amivantamab + lazertinib (EGFR inhibitor); Amivantamab + lazertinib + carboplatin/pemetrexed | DLT, AEs, ORR, DOR |
 NCT05299125 (AMIGO-1) | 2 | 49 | Amivantamab + lazertinib + carboplatin/pemetrexed | PFS |
 NCT04988295 (MARIPOSA-2) | 3 | 500 | Amivantamab + lazertinib + carboplatin/pemetrexed; Carboplatin/pemetrexed; Amivantamab + carboplatin/pemetrexed; | PFS |