Table VII.
On-going clinical trials of ALK-TKIs in NSCLC.
| NCT | Drug | Identifier | Sponsor | No. of samples | Phase | Primary endpoint |
|---|---|---|---|---|---|---|
| NCT03874273 | Crizotinib | Inflammatory myofibroblastic tumour | Federal Research Institute of Pediatric Hematology, Oncology and Immunology | 25 | II/III | ORR |
| NCT03620643 | Crizotinib | Lobular breast carcinoma gastric cancer | Royal Marsden NHS Foundation Trust | 58 | II | Percentage of participants with objective responses |
| NCT03088930 | Crizotinib | Lung cancer, NSCLC | University of Colorado, Denver | 18 | II | Objective tumour response rate |
| NCT03646994 | Crizotinib | ROS1 arranged non-squamous NSCLC | Hunan Province Tumor Hospital | 40 | II | PFS |
| NCT03672643 | Crizotinib | ALK or ROS1-positive NSCLC | Pfizer | 75 | IV | Long-term safety of crizotinib |
| NCT02419287 | Crizotinib | Anaplastic large cell lymphoma, ALK-positive | University of Milano Bicocca | 12 | II | ORR Duration |
| NCT03647111 | Crizotinib | ALK rearranged non-squamous NSCLC | Hunan Province Tumor Hospital | 120 | II | PFS |
| NCT03052608 | Lorlatinib/Crizotinib | ALK-positive NSCLC | Pfizer | 280 | III | PFS |
| NCT02201992 | Crizotinib | Stage IB-IIIA NSCLC that has been removed by surgery and ALK fusion mutations | ECOG-ACRIN Cancer Research Group | 168 | III | OS |
| NCT02679170 | Crizotinib | Advanced/Metastatic NSCLC | Pfizer | 100 | II | Incidence of ALK-positive NSCLC PFS |
| NCT03087448 | Ceritinib + Trametinib | NSCLC | University of California, San Francisco | 69 | I/II | MTD |
| NCT02299505 | Ceritinib | NSCLC | Novartis Pharmaceuticals | 306 | I | Plasma concentration of ceritinib |
| NCT01828099 | Ceritinib/Chemotherapy | NSCLC | Novartis Pharmaceuticals | 375 | III | PFS |
| NCT02513667 | Ceritinib | ALK-positive NSCLC | University of Texas Southwestern Medical Center | 33 | II | PFS |
| NCT02393625 | Ceritinib With Nivolumab | ALK-positive NSCLC | Novartis Pharmaceuticals | 57 | I | MTD, ORR |
| NCT01828112 | Ceritinib/Chemotherapy | NSCLC previously treated with chemotherapy (platinum doublet) and crizotinib | Novartis Pharmaceuticals | 232 | III | PFS |
| NCT03501368 | Ceritinib | Melanoma Unresectable Melanoma Advanced Melanoma | H. Lee Moffitt Cancer Center and Research Institute | 27 | II | ORR |
| NCT03611738 | Ceritinib + Docetaxel | ALK-negative, EGFR WT advanced NSCLC | H. Lee Moffitt Cancer Center and Research Institute | 48 | I | MTD Phase Ib: OR |
| NCT02321501 | Ceritinib + Everolimus | ALK-positive locally advanced or metastatic solid tumors or stage IIIB-IV NSCLC | M.D. Anderson Cancer Center | 66 | I | MTD |
| NCT03399487 | Ceritinib | NSCLC harbouring ROS1 rearrangement | Yonsei University | 46 | II | ORR |
| NCT01964157 | Ceritinib | NSCLC, cancer harbouring ROS1 rearrangement | Yonsei University | 32 | II | ORR |
| NCT03445000 | Alectinib | Advanced NSCLC | European Thoracic Oncology Platform | 44 | II | Best overall response |
| NCT02521051 | Alectinib + Bevacizumab | NSCLC | Massachusetts General Hospital | 43 | I/II | RP2D |
| NCT03202940 | Alectinib + Cobimetinib | Advanced ALK-rearranged (ALK+) NSCLC | Massachusetts General Hospital | 31 | IB/II | MTD |
| NCT03271554 | Alectinib | ALK-positive, locally advanced or metastatic NSCLC | Hoffmann-La Roche | 167 | II | Percentage of participants with AEs |
| NCT03596866 | Brigatinib/Alectinib | ALK+NSCLC who have progressed on crizotinib | Ariad Pharmaceuticals | 246 | III | PFS |
| NCT03194893 | Alectinib/Crizotinib | ALK+NSCLC rearranged during transfection (RET)-positive cancer | Hoffmann-La Roche | 200 | III | Number of patients with SAEs, non-SAEs and AEs of special interest |
| NCT03420742 | Brigatinib | ALK-positive or ROS1-positive solid tumors | Ariad Pharmaceuticals | 20 | I | AUC, Cmax, Tmax |
| NCT03410108 | Brigatinib | ALK-positive NSCLC | Takeda | 110 | II | ORR 12 months PFS Rate |
| NCT03535740 | Brigatinib | ALK+, advanced NSCLC progressed on alectinib or ceritinib (ALTA-2) | Ariad Pharmaceuticals | 103 | II | ORR |
| NCT03596866 | Brigatinib/Alectinib | Advanced ALK+NSCLC participants who have progressed on crizotinib (ALTA-3) | Ariad Pharmaceuticals | 246 | III | PFS |
| NCT02706626 | Brigatinib | NSCLC | Criterium, Inc. | 120 | II | ORR |
| NCT02094573 | Brigatinib | ALK-positive, NSCLC previously, treated with Crizotinib | Ariad Pharmaceuticals | 222 | II | ORR |
| NCT01449461 | Brigatinib | Antitumour activity of the oral ALK/EGFR | Ariad Pharmaceuticals | 137 | I/II | RP2D ORR |
| NCT03707938 | Brigatinib | Patients with Stage IV or recurrent NSCLC | M.D. Anderson Cancer Center | 35 | I | Incidence of AE |
| NCT03389399 | Brigatinib | NSCLC | Academic Thoracic Oncology Medical Investigators Consortium | 43 | I | The incidence of EOPEs (time frame: 8 days) |
| NCT03546894 | Any FDA Approved ALK Inhibitors | Anaplastic lymphoma kinase-positive Carcinoma NSCLC | Millennium Pharmaceuticals, Inc. | 160 | II | Prescriber-confirmed PFS |
| NCT03909971 | Lorlatinib | ALK inhibitor-treated ALK-positive NSCLC | Pfizer | 100 | II | OR |
| NCT03505554 | Lorlatinib | Relapsed ALK-positive lymphoma | University of Milano Bicocca | 12 | II | ORR |
| NCT04127110 | Lorlatinib | ALK-positive NSCLC patients | European Organisation for Research and Treatment of Cancer-EORTC | 84 | II | PFS |
| NCT03726333 | Lorlatinib | Advanced cancers | Pfizer | 76 | I | Plasma lorlatinib AUC24 at steady state |
| NCT03961997 | Lorlatinib | Healthy participants | Pfizer | 16 | I | AEs |
| NCT03439215 | Lorlatinib | Crizotinib pretreated ROS1-positive NSCLC | Fondazione Ricerca Traslazionale | 20 | II | Response rate to PF-06463922 in patients with ROS1 translocation resistant to crizotinib |
| NCT02927340 | Lorlatinib | Advanced ALK and ROS1 rearranged lung cancer with CNS metastasis | Massachusetts General Hospital | 30 | II | Intracranial disease control rate |
| NCT03107988 | Lorlatinib | Neuroblastoma | New Approaches to Neuroblastoma Therapy Consortium | 40 | I | RP2D, AE |
| NCT03542305 | Lorlatinib | Renal impairment | Pfizer | 32 | I | AUC, Cmax |
| NCT03727477 | Lorlatinib | NSCLC | Intergroupe Francophone de Cancerologie Thoracique | 250 | II | PFS |
| NCT03796260 | Entrectinib | Healthy participants | Genentech, Inc. | 14 | I | AUC, Cmax |
| NCT02568267 | Entrectinib | Solid tumours harbouring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK gene rearrangements (fusions) (STARTRK-2) | Hoffmann-La Roche | 300 | II | ORR |
| NCT02650401 | Entrectinib | Children and adolescents with solid tumours CNS tumours | Hoffmann-La Roche | 65 | I | MTD, RP2D, ORR |
| NCT02767804 | Ensartinib | NSCLC | Xcovery Holding Company, LLC | 290 | III | PFS |
| NCT04056572 | TQ-B3139 | ALK-positive NSCLC previously treated with Crizotinib | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | 135 | II | ORR |
| NCT04009317 | TQ-B3139 | ALK-positive NSCLC | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | 260 | III | PFS |
ORR, overall response rate; NSCLC, non-small-cell lung cancer; ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; ROS1, c-ros oncogene 1; NTRK, neurotrophic tyrosine kinase; CNS, central nervous system; PFS, progression-free survival; OS, overall survival; MTD, maximum tolerated dose; OR, overall response; RP2D, recommended phase II dose; AEs, adverse events; SAEs, serious adverse events; non-SAEs, non-serious adverse events; EOPEs, early onset pulmonary events; AUC, area under the curve; Cmax, maximum plasma concentration; Tmax, time to achieve peak concentration.