Table 1.
Ongoing trials targeting IPM with targetable mutations.
| Targeted Mutations | Trial | Phase | Population | Investigational Drug(s) | Total n | Primary Outcome | Comments |
|---|---|---|---|---|---|---|---|
| ALK, ROS1 | NCT02927340 | II | NSCLC | Loratinib | 30 | Intracranial disease control rate | |
| ALK, ROS1 | NCT01970865 | I/II | NSCLC | PF-06463922 vs. Crizotinib monotherapy | 334 | Participants with DLT, percentage of participants with overall and intracranial ORR | PF-0643922—ALK/ROS1 inhibitor |
| ALK, ROS1, or NTRK1-3 | NCT03093116 | I/II | Any IPM | Repotrectinib | 450 | DLT, recommended Phase II dose, ORR | Multiple arms comparing prior TKI and/or chemotherapy and treatment naïve |
| ALK, ROS1, NTRK1-3 | NCT05004116 | I/II | Any IPM | Repotrectinib + Irinotecan + Temozolomide | 50 | Incidence of DLT, MTD | |
| EGFR | NCT03769103 | II | NSCLC | SRS + Osimertinib vs. Osimertinib monotherapy | 76 | Intracranial PFS | Treatment naïve brain mets included |
| ROS1 | NCT04621188 | II | NSCLC | Loratinib | 84 | ORR | Recurrence after failure of first-line TKI |
| ROS1 | NCT03612154 | II | NSCLC | Loratinib | 35 | ORR | |
| ROS1 | NCT04919811 | II | NSCLC or other IPM | Taletrectinib (DS-6051b) | 119 | ORR | |
| ROS1, NTRK | NCT02675491 | I | Any IPM | DS-6051b | 15 | Number and severity of adverse events | |
| CDK, PI3K, NTRK/ROS1 | NCT03994796 | II | Any IPM | Abemaciclib or Paxalisib or Entrectinib | 150 | ORR | CDK population—Ademaciclib, PI3K—Paxalisib, NTRK/ROS1—Entrectinib |
| KRAS, EGFR | NCT01859026 | I/IB | NSCLC | Erlotinib + MEK162 | 43 | MTD | |
| KRAS | NCT03299088 | I | NSCLC | Pembrolizumab + Trametinib | 15 | Incidence of DLT | |
| KRAS | NCT03170206 | I/II | NSCLC | Palbociclib or Binimetinib monotherapy vs. combination therapy | 72 | MTD, safety and tolerability, PFS | CDK4/6 inhibitor + MEK inhibitor |
| KRAS | NCT03808558 | II | NSCLC | TVB-2640 | 12 | Disease control rate and response rate | |
| KRAS | NCT04111458 | I | Any IPM | BI-1701963 monotherapy vs. co-administration with Trametinib | 80 | MTD based on DLT, number of patients with DLT, ORR | |
| KRASG12C | NCT03785249 | I/II | Any IPM | MRTX849 (Adagrasib) monotherapy vs. combination therapy with Pembrolizumab, Cetuximab, or Afatinib | 565 | Safety, pharmacokinetics, and clinical activity/efficacy of MRTX849 | |
| CDK | NCT02896335 | II | Any IPM | Palbociclib | 30 | Clinical benefit rate (intracranial) | |
| HER-2 negative | NCT04647916 | II | Breast cancer | Sacituzumab Govitecan | 44 | ORR | |
| BRAFV600 | NCT03911869 | II | Melanoma | Encorafebib + Binimetinib vs. high dose | 13 | Incidence of DLT, incidence and severity of AE, incidence of dose modifications and discontinuations due to AE, brain metastasis response rate | |
| Checkpoint inhibition | NCT03340129 | II | Melanoma | Ipilimumab + nivolumab w/ RT vs. Ipilimumab + Nivolumab alone | 218 | Neurological specific cause of death |
AE: adverse effects, DLT: dose-limiting toxicity, IPM: intraparenchymal metastases, MTD: maximum tolerated dose, NSLC: non-small cell lung cancer, ORR: overall response rate, PFS: progression free survival, TKI: tyrosine kinase inhibitor.