Table 1.
Adverse events (AEs) (Total n) |
|||||||
---|---|---|---|---|---|---|---|
Therapeutic agent |
Trial (Status)* |
Patient population |
Response |
AE |
N(%) |
DLTs, Discontinued treatment N(%) |
Reference |
Urelumab (BMS-663513) | Monotherapy | ||||||
NCT00309023 (Terminated) | Metastatic or locally advanced solid tumors | 3 PRs (18C mo, 3C mo, 1.5C mo) | Integrated for the three trials | ||||
4 SD (10 mo, 6 mo, 6 mo, 4+ mo) | 0.1 mg/kg (n = 61) | ||||||
Any grade ≤ 4 AE (most common) | |||||||
Fatigue | 10(16) | 7(11) | |||||
Nausea | 8(13) | discontinued due to a treatment-related AE | |||||
Increased AST | 5(8) | ||||||
Decreased Appetite | 5(8) | ||||||
Asthenia | 5(8) | ||||||
Any grade ≤ 4 SAE | |||||||
Increased ALT | 1(2) | ||||||
|
|
|
|
Erysipelas |
]1(2) |
|
|
NCT00612664 (Completed) | Melanoma | Terminated in Dec 2008 following two hepatotoxicity-related deaths (≥1 mg/kg) | 0.3 mg/kg (n = 56) | ||||
Any grade ≤ 4 AE (most common) | |||||||
Increased AST | 8(14) | 5(9) | |||||
Fatigue | 8(14) | discontinued due to a treatment-related AE | 42-44 | ||||
Increased ALT | 6(11) | ||||||
Rash | 4(7) | ||||||
Pruritus | 3(5) | ||||||
Any grade ≤ 4 SAE | |||||||
Increased ALT | 2(4) | ||||||
Increased AST | 2(4) | ||||||
Abnormal LFT | 1(2) | ||||||
Acute hepatitis | 1(2) | ||||||
|
|
|
|
Enteritis |
1(2) |
|
|
NCT01471210 (Ongoing, not recruiting) | Advanced solid tumors or r/r B-cell NHL | No updates yet | ≥ 1 mg/kg (n=229) | ||||
Any grade ≤ 4 AE (most common) | |||||||
Increased AST | 62(27) | 37(16) | |||||
Increased ALT | 61(27) | discontinued due to a treatment-related AE | |||||
Fatigue | 55(24) | ||||||
Rash | 45(20) | ||||||
Nausea | 31(14) | ||||||
Any grade ≤ 4 SAE (most common) | |||||||
Increased AST | 12(5) | ||||||
Increased ALT | 11(5) | ||||||
Neutropenia | 7(3) | ||||||
Thrombocytopenia | 5(2) | ||||||
Febrile neutropenia | 4(2) | ||||||
|
Combination therapy with rituximab |
|
|
|
|
|
|
|
NCT01775631(Ongoing, not recruiting) |
r/r B-cell NHL |
|
No updates yet |
|
|
45 |
PF-05082566 | NCT01307267 (Recruiting) | Monotherapy | |||||
Solid tumors or B-cell NHL | (n = 34) | No DLTs | 46 | ||||
Grade 1 | |||||||
24/34 evaluable for response: | Rash | 3(9) | |||||
1 MR (0.06 mg/kg) | Fever | 2(6) | |||||
1 PR (0.6 mg/kg) | Nausea/vomiting | 2(6) | |||||
7 SD (across multiple doses) | Weight loss | 1(13) | |||||
Headache | 1(13) | ||||||
Fatigue | 1(13) | ||||||
Thrombocytopenia | 1(13) | ||||||
|
|
|
|
No Grade 2 or higher |
|
|
|
Combination therapy with rituximab | |||||||
(n=38) | No DLTs | 47 | |||||
All grades | |||||||
CD20-positive NHL | Up to 2.4 mg/kg:[]ORR = 21% (6/28) | Fatigue | 9(24) | No patient discontinued due to treatment-related AEs | |||
Rituximab-refractory**: | Rash | 4(11) | |||||
ORR = 29% (4/14) 2 CR (0.03 and 0.12 mg/kg), | Headache | 3(8) | |||||
DR>2 years 2 PR | Lymphopenia | 3(8) | |||||
Thrombocytopenia | 2(5) | ||||||
Neutropenia | 1(3) | ||||||
Grade 3 | |||||||
Lymphopenia | 1(3) | ||||||
Thrombocytopenia | 1(3) | ||||||
Neutropenia | 1(3) | ||||||
*Trial status update as of January 2016.
**Rituximab-refractory is defined as no response (PD or SD) to the prior therapy or PD during or within 6 mo of the last dose of rituximab.