Summary of safety and immune-mediated AEs in the safety analysis population*
| n (%) | NIVO+IPI (n=135) | NIVO (n=76) | ||||||||||
| tTMB-H (n=94) | bTMB-H (n=83) | tTMB-H (n=50) | bTMB-H (n=47) | |||||||||
| Any grade | Grade 3/4 | Grade 5 | Any grade | Grade 3/4 | Grade 5 | Any grade | Grade 3/4 | Grade 5 | Any grade | Grade 3/4 | Grade 5 | |
| All causality | 93 (98.9) | 50 (53.2) | 10 (10.6) | 82 (98.8) | 47 (56.6) | 14 (16.9) | 50 (100.0) | 19 (38.0) | 6 (12.0) | 45 (95.7) | 19 (40.4) | 4 (8.5) |
| Drug-related AE | ||||||||||||
| 30 days | 78 (83.0) | 27 (28.7) | – | 64 (77.1) | 28 (33.7) | – | 27 (54.0) | 4 (8.0) | – | 28 (59.6) | 1 (2.1) | – |
| 100 days | 78 (83.0) | 27 (28.7) | – | 65 (78.3) | 31 (37.3) | – | 27 (54.0) | 4 (8.0) | – | 28 (59.6) | 1 (2.1) | – |
| SAE | 45 (47.9) | 29 (30.9) | 10 (10.6) | 51 (61.4) | 32 (38.6) | 14 (16.9) | 16 (32.0) | 10 (20.0) | 6 (12.0) | 16 (34.0) | 10 (21.3) | 4 (8.5) |
| AE leading to discontinuation | 25 (26.6) | 19 (20.2) | 3 (3.2) | 32 (38.6) | 23 (27.7) | 4 (4.8) | 6 (12.0) | 4 (8.0) | 1 (2.0) | 4 (8.5) | 3 (6.4) | 0 |
| Non-endocrine imAE | ||||||||||||
| Pneumonitis | 1 (1.1) | – | – | – | – | – | 1 (2.0) | – | – | – | – | – |
| Diarrhea/colitis | 7 (7.4) | 4 (4.3) | – | 5 (6.0) | 4 (4.8) | – | 4 (8.0) | – | – | 1 (2.1) | – | – |
| Hepatitis | 6 (6.4) | 4 (4.3) | – | 5 (6.0) | 2 (2.4) | – | 1 (2.0) | 1 (2.0) | – | – | – | – |
| Nephritis and renal dysfunction | 1 (1.1) | – | – | – | – | – | – | – | – | – | – | – |
| Rash | 10 (10.6) | 2 (2.1) | – | 7 (8.4) | 1 (1.2) | – | 3 (6.0) | – | – | 1 (2.1) | – | – |
| Hypersensitivity | 2 (2.1) | 1 (1.1) | – | 1 (1.2) | – | – | 1 (2.0) | – | – | 2 (4.3) | – | – |
| Endocrine imAE | ||||||||||||
| Adrenal insufficiency | 4 (4.3) | – | – | 6 (7.2) | 3 (3.6) | – | – | – | – | – | – | – |
| Hypothyroidism | 13 (13.8) | – | – | 9 (10.8) | 1 (1.2) | – | 8 (16.0) | – | – | 8 (17.0) | – | – |
| Thyroiditis | 2 (2.1) | – | – | 3 (3.6) | 1 (1.2) | – | 1 (2.0) | – | – | 1 (2.1) | – | – |
| Diabetes mellitus | – | – | † | – | – | † | – | – | – | – | – | – |
| Hyperthyroidism | 10 (10.6) | 1 (1.1) | – | 8 (9.6) | 2 (2.4) | – | 1 (2.0) | – | – | 1 (2.1) | – | – |
| Hypophysitis | 2 (2.1) | 1 (1.1) | – | 3 (3.6) | 2 (2.4) | – | – | – | – | – | – | – |
*The safety analysis population comprises the 211 patients who received at least one dose of study drug; the tTMB-H and bTMB-H populations overlap.
†One patient who was in both the tTMB-H and bTMB-H cohorts was hospitalized due to Grade 4 hyperglycemia on Study Day 24 after initiation of nivolumab (240 mg) and ipilimumab (122 mg) combination therapy. The patient subsequently died of hyperglycemia.
AE, adverse event; bTMB-H, high blood tissue mutational burden; imAE, immune-mediated AE; IPI, ipilimumab; NIVO, nivolumab; SAE, serious AE; tTMB-H, high tissue tumor mutational burden.