Table 1.
Clinical activity of currently FDA approved targeted agents.
| Clinical Trial | Trial Type | Driver Mutation | Treatment Arms | Clinical Outcomes | Most Frequent AEs (All Grades) |
|---|---|---|---|---|---|
| GEOMETRY mono-1 | Phase 2, multicenter, multi-cohort, single-arm, non-randomized, open-label study | METex14 skipping mutation | Capmatinib | Pretreated pts: ORR 41%, DoR 9.7, mPFS 5.4 m. Treatment naïve: ORR 68%, DoR 12.6, mPFS 12.4 m. |
Peripheral edema, nausea, vomiting, creatinine increase. |
| VISION | Phase 2, multicenter, multi-cohort, single-arm, non-randomized, open-label study | METex14 skipping mutation | Tepotinib | Combined biopsy: ORR by ICR 46%, DoR 11.1 m, mPFS 8.5 m. Liquid biopsy: ORR by ICR 48%, DoR 9.9 m, mPFS 8.5 m. Tissue biopsy: ORR by ICR 50%, DoR 15.7 m, mPFS 11 m. |
Peripheral edema, nausea, diarrhea, creatinine increase. |
| LIBRETTO-001 | Phase 1/2 trial, international, open-label study | RET fusion | Selpercatinib | ORR by ICR 64%, DoR 17.5 m, mPFS 18.4 m. | Diarrhea, AST increase, dry mouth, hypertension, fatigue. |
| ARROW | Phase 1/2, multi-cohort, international, open-label study | RET fusion | Pralsetinib | Pretreated: ORR 61%, DoR NR, mPFS 17.1 m. Treatment naïve: ORR 70%, DoR 9.0 m, 9.1 m. |
AST/ALT increase, anemia, leucopenia, fatigue, constipation. |
| LOXO-TRK-14001 | Phase 1/2, multi-cohort, international, open-label study | NTRK gene fusion | Larotrectinib * | Overall population: ORR 75%, DoR NR, mPFS NR. (7 lung cancer pts enrolled) |
AST/ALT increase, anemia, neutropenia, weight increase. |
|
SCOUT/
NAVIGATE |
Phase 1/2, multicenter, multi-cohort, single-arm, non-randomized, open-label study | NTRK gene fusion | Larotrectinib * | ORR 30%, DCR 70%, mPFS 18.3 m, mOS NR. | AST/ALT increase, leucopenia, neutropenia, vomiting. |
|
STARTRK-1, STARTRK-2, ALKA-372-001
(Pooled analysis) |
Phase 1/2, multicenter, single-arm, non-randomized, open-label study | NTRK gene fusion, ROS1 rearrangement | Entrectinib | Overall population: ORR 59.3%, DoR 12.9, mPFS 12.9 m, mOS 23.9 m. | Fatigue, dysgeusia, paresthesia, nausea, myalgia. |
| CodeBreak 100 | Phase 2, multicenter, international, single arm, open-label study | KRASG12C mutation | Sotorasib | ORR by ICR 37.4%, DCR 80.5%, mPFS 6.7 m. | AST/ALT increase, leucopenia, anemia, diarrhea, myalgia, nausea, fatigue, hepatotoxicity, cough. |
Abbreviations: ORR, objective response rate; pts, patients; mPFS, median progression-free survival; mOS, median overall survival; m, months; AEs, adverse events; DoR, duration of response; ICR, independent central review; AST, aspartate aminotransferase; ALT, alanine transferase; NR, not reached; DCR, disease control rate. * Larotrectinib received agnostic approval for NTRK fusion-positive tumors.