Table 2.
Treatment-related adverse events
| Dose-escalation phase (n = 66) | Expansion phase: oleclumab 40 mg/kg + durvalumab 10 mg/kg (n = 126) | ||||
|---|---|---|---|---|---|
| TRAEa, n (%) | Single-agent oleclumab 5–40 mg/kg (n = 42) | Oleclumab 5–40 mg/kg + durvalumab 10 mg/kg (n = 24) | MSS-CRC (n = 42) | PDAC (n = 42) | EGFRm NSCLC (n = 42) |
| Any TRAE | 23 (55) | 13 (54) | 25 (60) | 24 (57) | 19 (45) |
| Any Grade 3–4 TRAE | 3 (7) | 5 (21) | 8 (19) | 7 (17) | 5 (12) |
| Death due to TRAE | 0 | 0 | 1 (2)d | 0 | 0 |
| Any serious TRAE | 0 | 1 (4) | 2 (5) | 5 (12) | 3 (7) |
| Any TEAE leading to discontinuationb | 2 (5) | 2 (8) | 3 (7) | 1 (2) | 2 (5) |
| TRAEs in > 10% of patients in any cohortc | |||||
| Fatigue | 7 (17) | 6 (25) | 7 (17) | 5 (12) | 7 (17) |
| Diarrhea | 0 | 2 (8) | 5 (12) | 4 (10) | 2 (5) |
| AST increased | 2 (5) | 3 (13) | 4 (10) | 2 (5) | 1 (2) |
| Vomiting | 2 (5) | 3 (13) | 2 (5) | 5 (12) | 0 |
| Nausea | 4 (10) | 3 (13) | 4 (10) | 0 | 0 |
| Rash | 1 (2) | 1 (4) | 3 (7) | 1 (2) | 5 (12) |
| Grade 3–4 TRAEs in ≥ 1 patient in any cohortc | |||||
| Aspartate aminotransferase increased | 0 | 2 (8) | 1 (2) | 1 (2) | 1 (2) |
| Hyperglycemia | 1 (2) | 1 (4) | 0 | 1 (2) | 0 |
| Lipase increased | 1 (2) | 0 | 2 (5) | 0 | 0 |
| Alanine aminotransferase increased | 0 | 1 (4) | 1 (2) | 0 | 0 |
| Amylase increased | 1 (2) | 0 | 0 | 0 | 1 (2) |
| Blood alkaline phosphatase increased | 0 | 0 | 1 (2) | 1 (2) | 0 |
| Acute kidney injury | 0 | 0 | 0 | 0 | 1 (2) |
| Anemia | 0 | 0 | 0 | 0 | 1 (2) |
| Asthenia | 0 | 0 | 0 | 1 (2) | 0 |
| Blood bilirubin increased | 0 | 0 | 0 | 1 (2) | 0 |
| Blood creatinine increased | 0 | 0 | 0 | 0 | 1 (2) |
| Colitis | 0 | 0 | 0 | 1 (2) | 0 |
| Cytokine release syndrome | 0 | 0 | 1 (2) | 0 | 0 |
| Dyspnea | 0 | 0 | 1 (2) | 0 | 0 |
| Embolic stroke | 0 | 0 | 0 | 1 (2) | 0 |
| Embolism | 0 | 0 | 0 | 1 (2) | 0 |
| Eosinophilic fasciitis | 0 | 0 | 1 (2) | 0 | 0 |
| Gamma-glutamyltransferase increased | 1 (2) | 0 | 0 | 0 | 0 |
| Headache | 0 | 1 (4) | 0 | 0 | 0 |
| Hepatitis | 0 | 0 | 0 | 0 | 1 (2) |
| Hypertension | 0 | 0 | 0 | 0 | 1 (2) |
| Hyponatremia | 0 | 0 | 1 (2) | 0 | 0 |
| Immune-mediated hepatitis | 0 | 0 | 0 | 1 (2) | 0 |
| Peripheral edema | 0 | 0 | 1 (2) | 0 | 0 |
| Renal failure | 0 | 0 | 0 | 0 | 1 (2) |
| Systemic inflammatory response syndrome | 0 | 0 | 1 (2) | 0 | 0 |
| Thrombocytopenia | 0 | 1 (4) | 0 | 0 | 0 |
| Vomiting | 0 | 0 | 0 | 1 (2) | 0 |
| Serious TRAEs in ≥ 1 patient in any cohortc | |||||
| Abdominal pain | 0 | 0 | 0 | 1 (2) | 0 |
| Acute kidney injury | 0 | 0 | 0 | 0 | 1 (2) |
| Asthenia | 0 | 0 | 0 | 1 (2) | 0 |
| Blood creatinine increased | 0 | 0 | 0 | 0 | 1 (2) |
| Colitis | 0 | 0 | 0 | 1 (2) | 0 |
| Embolic stroke | 0 | 0 | 0 | 1 (2) | 0 |
| Embolism | 0 | 0 | 0 | 1 (2) | 0 |
| Eosinophilic fasciitis | 0 | 0 | 1 (2) | 0 | 0 |
| Hepatitis | 0 | 0 | 0 | 0 | 1 (2) |
| Immune-related hepatitis | 0 | 0 | 0 | 1 (2) | 0 |
| Pulmonary embolism | 0 | 0 | 0 | 0 | 1 (2) |
| Renal failure | 0 | 0 | 0 | 0 | 1 (2) |
| Systemic inflammatory response syndrome | 0 | 0 | 1 (2) | 0 | 0 |
| Thrombocytopenia | 0 | 1 (4) | 0 | 0 | 0 |
| Vomiting | 0 | 0 | 0 | 1 (2) | 0 |
AST aspartate aminotransferase, EGFRm epidermal growth factor receptor-mutant, MSS-CRC microsatellite-stable colorectal cancer, NSCLC non-small-cell lung cancer, PDAC pancreatic ductal adenocarcinoma, TEAE treatment-emergent adverse event, TRAE treatment-related adverse event
aConsidered at least possibly related to oleclumab
bDiscontinuation of oleclumab. These treatment-emergent AEs included: small intestinal obstruction in 1 patient and pulmonary embolism in 1 patient in the oleclumab 20 mg/kg monotherapy cohort; increased aspartate aminotransferase and increased blood bilirubin in 1 patient in the oleclumab 5 mg/kg + durvalumab 10 mg/kg group and increased alanine aminotransferase and increased blood alkaline phosphatase in 1 patient in the oleclumab 40 mg/kg + durvalumab 10 mg/kg group; eosinophilic fasciitis, peripheral edema, and systemic inflammatory response syndrome in 1 patient each in the MSS-CRC expansion cohort; immune-mediated hepatitis in 1 patient in the PDAC expansion cohort, and hepatitis and renal failure in 1 patient each in the EGFRm NSCLC expansion cohort
cTRAEs and serious TRAEs listed in order of total overall frequency across all cohorts
dSystemic inflammatory response syndrome