Introduction
Methods
Study design
Patients
Treatment
Assessments
Statistical considerations
Results
Patient demographics and disposition
Dose-escalation phase (n = 66) | Expansion phase: oleclumab 40 mg/kg + durvalumab 10 mg/kg (n = 126) | ||||
---|---|---|---|---|---|
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) | |
Age, median (range), years | 59.5 (36–81) | 55 (32–71) | 53 (25–80) | 63.5 (32–77) | 61.5 (34–83) |
Sex, n (%) | |||||
Male | 20 (48) | 9 (38) | 19 (45) | 16 (38) | 17 (40) |
Female | 22 (52) | 15 (63) | 23 (55) | 26 (62) | 25 (60) |
Race, n (%) | |||||
White | 33 (79) | 21 (88) | 32 (76) | 37 (88) | 10 (24) |
Black or African American | 3 (7) | 2 (8) | 4 (10) | 1 (2) | 1 (2) |
Asian | 2 (5) | 1 (4) | 5 (12) | 2 (5) | 30 (71) |
Other | 4 (10) | 0 | 1 (2) | 2 (5) | 1 (2)a |
ECOG PS, n (%) | |||||
0 | 23 (55) | 11 (46) | 24 (57) | 10 (24) | 8 (19) |
1 | 19 (45) | 13 (54) | 18 (43) | 32 (76) | 34 (81) |
Cancer type, n (%) | |||||
CRCb | 23 (55) | 12 (50) | 42 (100) | 0 | 0 |
PDAC | 19 (45) | 12 (50) | 0 | 42 (100) | 0 |
EGFRm NSCLC | 0 | 0 | 0 | 0 | 42 (100) |
Time since initial diagnosis, median (range), months | 26.1 (9.6–176.5) | 31.5 (5.3–78.7) | 36.7 (12.1–116.4) | 14.8 (4.4–90.3) | 26.0 (5.5–212.1) |
Number of target lesions, median (range) | 2 (1–5) | 2 (1–5) | 3 (1–5) | 2 (1–5) | 2 (1–5) |
Prior lines of therapy,c n (%) | |||||
1 | 2 (5) | 4 (17) | 1 (2) | 15 (36) | 9 (21) |
2 | 14 (33) | 7 (29) | 13 (31) | 22 (52) | 16 (38) |
3 | 16 (38) | 7 (29) | 12 (29) | 5 (12) | 11 (26) |
≥ 4 | 10 (24) | 6 (25) | 16 (38) | 0 | 6 (14) |
Smoking history – yes, n (%) | 16 (38) | 8 (33) | 12 (29) | 10 (24) | 12 (29) |
Dose escalation
Safety
Escalation cohorts
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 |