Table 1.
Patient Demographic and Baseline Characteristics
| Phase 1 Dose-Escalation (n = 16) | Phase 2 | All Patients | ||||
|---|---|---|---|---|---|---|
| Characteristic | 250 mg/m2 | 400 mg/m2 | 550 mg/m2 | 750 mg/m2 | ||
| (n = 3) | (n = 3) | (n = 7) | (n = 3) | (n = 27) | (n = 43) | |
| Median age, years (range) | 9 (7-13) | 15 (6-20) | 7 (6-17) | 10 (4-16) | 5 (2 months-19 years)a | 7 (2 months-20 years) |
| Sex, n (%) | ||||||
| Male | 2 (66.7) | 1 (33.3) | 5 (71.4) | 2 (66.7) | 12 (44.4) | 22 (51.2) |
| Female | 1 (33.3) | 2 (66.7) | 2 (28.6) | 1 (33.3) | 15 (55.6) | 21 (48.8) |
| Race, n (%) | ||||||
| White | 2 (66.7) | 2 (66.7) | 6 (85.7) | 3 (100.0) | 24 (88.9) | 37 (86.0) |
| Black or African American | 1 (33.3) | 1 (33.3) | 1 (14.3) | 0 | 2 (7.4) | 5 (11.6) |
| Other | 0 | 0 | 0 | 0 | 1 (3.7) | 1 (2.3) |
| Ethnicity, n (%) | ||||||
| Hispanic or Latino | 0 | 1 (33.3) | 0 | 0 | 3 (11.1) | 4 (9.3) |
| Non-Hispanic or Latino | 3 (100.0) | 2 (66.7) | 6 (85.7) | 2 (66.7) | 23 (85.2) | 36 (83.7) |
| Not stated | 0 | 0 | 0 | 1 (33.3) | 0 | 1 (2.3) |
| Unknown | 0 | 0 | 1 (14.3) | 0 | 1 (3.7) | 2 (4.7) |
| Karnofsky/Lansky score, n (%)b | ||||||
| 60 | 0 | 0 | 0 | 0 | 2 (7.4) | 2 (4.8) |
| 70 | 0 | 0 | 1 (16.7) | 0 | 1 (3.7) | 2 (4.8) |
| 80 | 0 | 1 (33.3) | 0 | 1 (33.3) | 8 (29.6) | 10 (23.8) |
| 90 | 0 | 1 (33.3) | 4 (66.7) | 2 (66.7) | 6 (22.2) | 13 (31.0) |
| 100 | 3 (100.0) | 1 (33.3) | 1 (16.7) | 0 | 10 (37.0) | 15 (35.7) |
| Prior systemic therapies, n (%) | ||||||
| Chemotherapy | 3 (100.0) | 3 (100.0) | 5 (71.4) | 3 (100.0) | 19 (70.4) | 33 (76.7) |
| Immunotherapy | 0 | 2 (66.7) | 4 (57.1) | 1 (33.3) | 4 (14.8) | 11 (25.6) |
| Targeted therapy | 0 | 2 (66.7) | 1 (14.3) | 0 | 0 | 3 (7.0) |
| Monoclonal antibody | 0 | 3 (100.0) | 2 (28.6) | 3 (100.0) | 4 (14.8) | 12 (27.9) |
| Radiation | 3 (100.0) | 3 (100.0) | 5 (71.4) | 2 (66.7) | 11 (40.7) | 24 (55.8) |
| Tumor type/histology, n (%) | ||||||
| Extracranial solid tumor | 1 (33.3) | 1 (33.3) | 2 (28.6) | 1 (33.3) | 7 (25.9) | 12 (27.9) |
| Infantile fibrosarcoma | 0 | 0 | 0 | 1 (33.3) | 1 (3.7) | 2 (4.7) |
| IMT | 0 | 0 | 2 (28.6) | 0 | 3 (11.1) | 5 (11.6) |
| Melanoma | 0 | 0 | 0 | 0 | 1 (3.7) | 1 (2.3) |
| Salivary gland adenocarcinoma | 1 (33.3) | 0 | 0 | 0 | 0 | 1 (2.3) |
| Spindle cell sarcoma | 0 | 1 (33.3) | 0 | 0 | 0 | 1 (2.3) |
| Myofibroblastic tumor | 0 | 0 | 0 | 0 | 1 (3.7) | 1 (2.3) |
| Infantile myofibroma | 0 | 0 | 0 | 0 | 1 (3.7) | 1 (2.3) |
| Primary CNS (brain) tumor | 0 | 0 | 0 | 0 | 16 (59.3) | 16 (37.2) |
| Glioblastoma | 0 | 0 | 0 | 0 | 3 (11.1) | 3 (7.0) |
| Astrocytoma | 0 | 0 | 0 | 0 | 4 (14.8) | 4 (9.3) |
| Ganglioglioma | 0 | 0 | 0 | 0 | 2 (7.4) | 2 (4.7) |
| Epithelioid glial neoplasm | 0 | 0 | 0 | 0 | 1 (3.7) | 1 (2.3) |
| Medulloblastoma | 0 | 0 | 0 | 0 | 1 (3.7) | 1 (3.7) |
| High-grade glioma NOS | 0 | 0 | 0 | 0 | 3 (11.1) | 3 (7.0) |
| Glioma NOS | 0 | 0 | 0 | 0 | 1 (3.7) | 1 (2.3) |
| Ganglioneuroblastoma | 0 | 0 | 0 | 0 | 1 (3.7) | 1 (2.3) |
| Neuroblastoma | 2 (66.7) | 2 (66.7) | 5 (71.4) | 2 (66.7) | 4 (14.8) | 15 (34.9) |
| Target gene fusion, n (%) | ||||||
| NTRK1/2/3 | 0 | 0 | 0 | 1 (33.3) | 14 (51.9) | 15 (34.9) |
| ROS1 | 0 | 0 | 1 (14.3) | 0 | 7 (25.9) | 8 (18.6) |
| ALK | 0 | 0 | 1 (14.3) | 0 | 2 (7.4) | 3 (7.0) |
| Non-fusion target gene alteration, n (%) | ||||||
| NTRK1c | 0 | 1 (33.3)d | 1 (14.3)d | 0 | 0 | 2 (4.7) |
| ROS1 | 0 | 0 | 0 | 0 | 0 | 0 |
| ALK | 0 | 0 | 1 (14.3) | 0 | 1 (3.7) | 2 (4.7) |
| Any target gene alteration, n (%) | ||||||
| NTRK1/2/3 | 0 | 1 (33.3) | 1 (14.3) | 1 (33.3) | 14 (51.9) | 17 (39.5) |
| ROS1 | 0 | 0 | 1 (14.3) | 0 | 7 (25.9) | 8 (18.6) |
| ALK | 0 | 0 | 2 (28.6) | 0 | 3 (11.1) | 5 (11.6) |
Abbreviations: ALK, anaplastic lymphoma kinase; CNS, central nervous system; IMT, inflammatory myofibroblastic tumor; NTRK, neurotrophic tyrosine receptor kinase; NOS, not otherwise specified; ROS1, ROS proto-oncogene 1.
aPatient aged 2 months received 250 mg/m2 dosage.
bn = 42; 1 patient in 550 mg/m2 dose group was excluded from Karnofsky/Lansky score category due to incorrect performance score scale for age.
cNo non-fusion gene alterations were identified in NTRK2 or 3.
dConsidered variants of unknown significance.