Table 2.
Dose levels explored, number of patients on each dose level, and whether DLTs were observed.
| Dose level | Cycle 0 dose (olaparib p.o. b.i.d.) | Cycle 1 + dose (olaparib p.o. b.i.d.; onalespib i.v. on days 1, 2, 8, 9, 15, and 16) | Total patients | Evaluable patients for DLTa | DLTs (aetiology) |
|---|---|---|---|---|---|
| DL0 | Olaparib 200 mg | Olaparib 200 mg; onalespib 20 mg/m2 | 3 | 3 | 0 |
| DL1 | Olaparib 200 mg | Olaparib 200 mg; onalespib 40 mg/m2 | 4 | 3 | 0 |
| DL2 | Olaparib 300 mg | Olaparib 300 mg; onalespib 40 mg/m2 | 6 | 3 | 0 |
| DL3 | Olaparib 300 mg | Olaparib 300 mg; onalespib 80 mg/m2 | 7 | 5 | 2 (both Gr3 anaemia) |
| DL2a | Olaparib 200 mg | Olaparib 200 mg; onalespib 80 mg/m2 | 3 | 3 | 0 |
| DL3a | Olaparib 200 mg | Olaparib 200 mg; onalespib 120 mg/m2 | 5 | 4 | 1 (Gr3 thrombocytopenia) |
aSeven patients were not evaluable for DLT assessment and were replaced. Of these seven patients, two patients developed small bowel obstruction related to disease progression during cycle 0 and 1 (DL1 and DL2), two patients withdrew consent during cycle 1 because of advanced disease (DL2 and DL3), two patients could not receive at least 75% of cycle 1 dosing because of advanced disease (DL2 and DL3a), and one patient assigned to dose level DL3 was erroneously treated with DL2 (this patient was replaced but remained on treatment on DL2, was followed for radiographic response and exhibited no DLT).