Table 2. . Summary of outcomes from various trials evaluating carfilzomib in relapsed myeloma.
| Trial | Previous therapy (median number of prior lines) | Regimen schedule | ORR (%) | Median PFS; (95% CI) months | Median OS (95% CI); months |
|---|---|---|---|---|---|
| PX-171-003-A1, Phase II, n = 257 |
Number of prior lines: 5 (1–20) BTZ: 100% LEN: 94% |
CFZ 20 mg/m2 (cycle 1), 27 mg/m2 (cycle 2+) Days 1, 2, 8, 9, 15, 16 every 4-week cycle |
24% CR: 0.4% VGPR: 5.1% PR: 18.3% |
3.7 (2.8–4.6) |
15.6 (13–19.2) |
| PX-171-004-A0, Phase II, (BTZ naive) Cohort 1: n = 59 Cohort 2: n = 67 |
Cohort 1: – Number of prior lines: 2 (1–4) – BTZ: 0% – LEN: 46% Cohort 2: – Number of prior lines: 2 (1–4) – BTZ: 4.3% – LEN: 70% |
Cohort 1: – CFZ 20 mg/m2– Days 1, 2, 8, 9, 15, 16 every 4-week cycle Cohort 2: – CFZ 20 mg/m2 (cycle 1), 27 mg/m2 (cycle 2+) – Days 1, 2, 8, 9, 15, 16 every 4-week cycle |
42.4% CR: 3.4% VGPR: 13.6% PR: 25.4% 52.2% CR: 1.5% VGPR: 26.9% PR: 23.9% |
8.3 (6–12.3) NR (11.3–NR) |
– – |
| PX-171-004-A1, Phase II (BTZ treated), n = 35 |
Number of prior lines: 3 (1–13) BTZ: 100% LEN: 37% |
CFZ 20 mg/m2 (cycle 1), 27 mg/m2 (cycle 2+) Days 1, 2, 8, 9, 15, 16 every 4-week cycle |
17.1% CR: 3.0% VGPR: 2.9% PR: 11.4% |
4.6 (2.1–11.1) |
29.9 (NR) |
| PX-171-005, Phase II (with renal impairment), n = 47 |
Number of prior lines: 5 (1–15) BTZ: 96% LEN: 88% |
CFZ 15 mg/m2 (cycle 1), 20 mg/m2 (cycle 2) and 27 mg/m2 (cycle 3+) Days 1, 2, 8, 9, 15, 16 every 4-week cycle |
27.7% CR: 0% VGPR: 0% PR: 25.5% |
– |
– |
| ASPIRE Phase III n = 792 Relapsed MM |
CFZ/LEN/Dex: – Number of prior lines: 2 (1–3) – BTZ: 65.9% – LEN: 19.9% LEN/Dex: – Number of prior lines: 2 (1–3) – BTZ: 65.7% – LEN: 19.7% |
CFZ 20 mg/m2 (cycle 1, days 1 and 2 only) then 27 mg/m2 thereafter Days 1, 2, 8, 9, 15, 16 every 4-week (cycle 1–12) Days 1, 2, 15, 16 every 4-week (cycle 13–18) LEN 25 mg (days 1–21) Dex 40 mg (days 1, 8, 15, 22) LEN 25 mg (days 1–21) Dex 40 mg (days 1, 8, 15, 22) |
87.1% CR: 31.8% VGPR: 69.9% 66.7% CR: 9.3% VGPR: 40.4% |
26.3 (23.2–30.5) 17.6 (15–20.6) |
2-year OS: 73.3% 2-year OS: 65% |
| PX-171-007, Phase Ib/II, n = 33 |
Number of prior lines: 5 (1–9) BTZ: N/A LEN: N/A |
CFZ 20–70 mg/m2 (extended infusion time) Days 1, 2, 8, 9, 15,16 every 4-week cycle |
60% CR: 3% VGPR: 12% PR: 21% |
– |
– |
| ENDEAVOUR, Phase III, n = 929, Relapsed MM |
CFZ/Dex: – Number of prior lines: 2 (1–2) – BTZ: 54% – LEN: 38% BTZ/Dex: Number of prior lines: 2 (1–2) – BTZ: 54% – LEN: 38% |
CFZ 20 mg/m2 (cycle 1, days 1 & 2 only) then 56 mg/m2 thereafter Days 1, 2, 8, 9, 15, 16 every 4 weeks Dex 20 mg (days 1, 2, 8, 9, 15, 16, 22, 23) BTZ 1.3 mg/m2; days 1, 4, 8, 11 every 3 weeks Dex 20 mg (days 1, 2, 4, 5, 8, 9, 11, 12) |
77% CR: 13% VGPR: 42% PR: 22% 63% CR: 6% VGPR: 22% PR: 34% |
18.7 (15.6–NE) 9.4 (8.4–10.4) |
– |
| CFZ/Pom/Dex, Phase I, n = 32, Relapsed MM |
Number of prior lines: 6 (1–15) BTZ: 97% LEN: 100% |
CFZ 20 mg/m2 (cycle 1, days 1 and 2 only) then 27–56 mg/m2 thereafter Days 1, 2, 8, 9, 15, 16 q4 week (cycle 1–6) Days 1, 2, 15, 16 q4 week (cycle 7 onward) Pom 4 mg (days 1–21) Dex 40 mg (days 1, 8, 15, 22) |
50% VGPR: 16% PR: 34% |
7.2 (3–9) |
20.6 (11.9–28.7) |
| CHAMPION-1, Phase I/II, Phase I = 27, Phase II = 89 |
Number of prior lines: 1 (1–3) BTZ: 83% LEN: 50% |
Phase I: CFZ 20 mg/m2 (cycle 1, day 1 only) then subsequent doses started at 45 mg/m2 and were escalated to 56, 70 or 88 mg/m2 Phase II: (MTD) of 70 mg/m2 Dex: 40 mg (days 1, 8, 15 and 22 of cycles 1–8) and omitted on day 22 from cycles ≥9 |
77% (at MTD) CR: 14% VGPR: 33% PR: 31% |
12.6 (9.0–NE) | – |
BTZ: Bortezomib; CFZ: Carfilzomib; CR: Complete response; Dex: Dexamethasone; LEN: Lenalidomide; MM: Multiple myeloma; MTD: Maximum tolerated dose; NE: Not evaluable; NR: No response; ORR: Overall response rate; OS: Overall survival; PFS: Progression-free survival; Pom: Pomalidomide; PR: Partial response; VGPR: Very good partial response.