Table 1.
Summary of NOTCH inhibitor trials and associated risk of hypophosphatemia
| Cancer | Pt no:/study type | Dose | Incidence of Hypophosphatemia |
|---|---|---|---|
| Desmoid tumor1 | 70, Phase 3 double-blind, placebo, RCT | Nirogacestat 150 mg BID | 42% in Rx arm |
| Advanced sarcoma2 | 67, Investigator-initiated trial, phase 1b/2 RCT | RO4929097 (monoRx): 34 RO4929097 + Vismodegib: 33 |
MonoRx arm: 38% Combination arm: 3% |
| Desmoid tumor3 | 17, Open-label, single-arm, Phase 2 | 150 mg BID | 76% Grade 2: 38% Grade 3: 62% |
| Metastatic breast4 | 15, Phase 1b dose-escalation trial | The dose escalated over 5 doses (20, 30, 45, 90, and 140 mg) | 46.7% Grade 3 AE 13.4% |
| Solid organ cancer5 | 36, open-label phase 1 dose-escalation study | Once daily dosing 0.3, 0.6, 1.2, 1.5, 2.0 mg Twice weekly 2, 4, 8 mg |
67% in once daily, 58% in weekly schedule |
AE, adverse events; monoRx, monotherapy; RCT, randomized control trial; Rx, treatment.