Introduction
Methods
Study design
Patient population
Endpoints and measurements
Statistics
Results
Patients
HLX07 dose level | ||||||
---|---|---|---|---|---|---|
50 mg (n = 3) | 100 mg (n = 3) | 200 mg (n = 3) | 400 mg (n = 3) | 600 mg (n = 3) | 800 mg (n = 4) | |
Mean age, years (SD) | 52.3 (14.6) | 62.3 (17.1) | 59.3 (3.8) | 47.3 (9.1) | 66.3 (9.6) | 61.5 (6.9) |
Males, n (%) | 3 (100.0) | 2 (66.7) | 2 (66.7) | 3 (100.0) | 2 (66.7) | 4 (100.0) |
Race, Asian, n (%) | 3 (100.0) | 3 (100.0) | 3 (100.0) | 3 (100.0) | 3 (100.0) | 4 (100.0) |
Mean weight, kg (SD) | 67.4 (8.8) | 65.6 (11.0) | 61.3 (11.7) | 70.8 (12.9) | 54.8 (19.8) | 64.3 (11.7) |
Mean height, cm (SD) | 165.3 (3.2) | 167.0 (10.8) | 163.0 (3.0) | 171.7 (7.4) | 161.3 (7.1) | 168.5 (6.8) |
Mean body mass index, kg/m2 (SD) | 24.8 (4.1) | 23.4 (1.0) | 23.0 (3.7) | 23.9 (3.0) | 20.9 (6.8) | 22.5 (2.7) |
WHO PS, n (%) | ||||||
0 | 0 | 1 (33.3) | 0 | 0 | 1 (33.3) | 2 (50.0) |
1 | 3 (100.0) | 2 (66.7) | 3 (100.0) | 3 (100.0) | 2 (66.7) | 1 (25.0) |
2 | 0 | 0 | 0 | 0 | 0 | 1 (25.0) |
Tumor type, n (%) | ||||||
Colorectal cancer | 1 (33.3) | 2 (66.7) | 0 | 1 (33.3) | 1 (33.3) | 0 |
Oesophageal carcinoma | 0 | 0 | 3 (100.0) | 1 (33.3) | 1 (33.3) | 0 |
Head and neck | 2 (66.7) | 0 | 0 | 0 | 1 (33.3) | 1 (25.0) |
Hepatocellular carcinoma | 0 | 0 | 0 | 0 | 0 | 3 (75.0) |
Pancreatic head carcinoma | 0 | 1 (33.3) | 0 | 0 | 0 | 0 |
Malignant neoplasm of thymus | 0 | 0 | 0 | 1 (33.3) | 0 | 0 |
Tumor stage (TNM), n (%) | ||||||
IIIa | 0 | 0 | 1 (33.3) | 0 | 0 | 0 |
IV | 1 (33.3) | 1 (33.3) | 1 (33.3) | 3 (100.0) | 1 (33.3) | 3 (75.0) |
IVa | 1 (33.3) | 1 (33.3) | 0 | 0 | 0 | 0 |
IVb | 0 | 1 (33.3) | 1 (33.3) | 0 | 1 (33.3) | 0 |
IVc | 1 (33.3) | 0 | 0 | 0 | 1 (33.3) | 1 (25.0) |
Prior lines of therapy, n (%) | ||||||
1–2 | 0 | 1 (33.3) | 1 (33.3) | 1 (33.3) | 2 (66.7) | 1 (25.0) |
≥3 | 3 (100.0) | 2 (66.7) | 2 (66.7) | 2 (66.7) | 1 (33.3) | 3 (75.0) |
Safety
HLX07 dose level | ||||||
---|---|---|---|---|---|---|
n (%) | 50 mg (n = 3) | 100 mg (n = 3) | 200 mg (n = 3) | 400 mg (n = 3) | 600 mg (n = 3) | 800 mg (n = 4) |
≥1 TEAE | 3 (100.0) | 3 (100.0) | 3 (100.0) | 3 (100.0) | 3 (100.0) | 4 (100.0) |
≥1 serious TEAE | 2 (66.7) | 3 (100.0) | 0 (0) | 1 (33.3) | 1 (33.3) | 4 (100.0) |
TEAEs occurring in >10% of total patients | ||||||
Fatigue | 2 (66.7) | 1 (33.3) | 2 (66.7) | 3 (100.0) | 3 (100.0) | 2 (50.0) |
Nausea | 1 (33.3) | 0 | 1 (33.3) | 2 (66.7) | 3 (100.0) | 1 (25.0) |
Cough | 1 (33.3) | 1 (33.3) | 1 (33.3) | 1 (33.3) | 0 | 2 (50.0) |
Paronychia | 0 | 0 | 2 (66.7) | 2 (66.7) | 2 (66.7) | 0 |
Vomiting | 2 (66.7) | 0 | 0 | 1 (33.3) | 2 (66.7) | 1 (25.0) |
Constipation | 1 (33.3) | 0 | 1 (33.3) | 2 (66.7) | 1 (33.3) | 0 |
Rash | 0 | 1 (33.3) | 2 (66.7) | 1 (33.3) | 1 (33.3) | 0 |
Acne | 0 | 0 | 0 | 2 (66.7) | 0 | 2 (50.0) |
Decreased appetite | 0 | 1 (33.3) | 0 | 2 (66.7) | 1 (33.3) | 0 |
Headache | 1 (33.3) | 0 | 0 | 2 (66.7) | 1 (33.3) | 0 |
Insomnia | 1 (33.3) | 2 (66.7) | 0 | 0 | 1 (33.3) | 0 |
Blood lactate dehydrogenase increased | 0 | 0 | 1 (33.3) | 1 (33.3) | 1 (33.3) | 0 |
Folliculitis | 0 | 0 | 1 (33.3) | 1 (33.3) | 1 (33.3) | 0 |
Hypomagnesaemia | 0 | 0 | 1 (33.3) | 1 (33.3) | 1 (33.3) | 0 |
Pyrexia | 0 | 1 (33.3) | 0 | 1 (33.3) | 1 (33.3) | 0 |
Asthenia | 0 | 0 | 0 | 1 (33.3) | 1 (33.3) | 0 |
Blood bilirubin increased | 0 | 1 (33.3) | 0 | 0 | 0 | 1 (25.0) |
Cellulitis | 0 | 0 | 0 | 0 | 1 (33.3) | 1 (25.0) |
Dermatitis acneiform | 0 | 0 | 0 | 0 | 1 (33.3) | 1 (25.0) |
Dehydration | 0 | 1 (33.3) | 0 | 1 (33.3) | 0 | 0 |
Diarrhea | 0 | 0 | 1 (33.3) | 1 (33.3) | 0 | 0 |
Dizziness | 0 | 0 | 0 | 1 (33.3) | 1 (33.3) | 0 |
Dyspnea | 1 (33.3) | 0 | 0 | 0 | 1 (33.3) | 0 |
Hematuria | 0 | 0 | 1 (33.3) | 1 (33.3) | 0 | 0 |
Hypertension | 1 (33.3) | 0 | 0 | 1 (33.3) | 0 | 0 |
Hypoesthesia | 0 | 0 | 0 | 1 (33.3) | 1 (33.3) | 0 |
Hypoglycemia | 0 | 1 (33.3) | 0 | 0 | 1 (33.3) | 0 |
Mucosal inflammation | 1 (33.3) | 0 | 0 | 0 | 1 (33.3) | 0 |
Myalgia | 0 | 0 | 0 | 2 (66.7) | 0 | 0 |
Neutrophil count decreased | 0 | 0 | 0 | 1 (33.3) | 0 | 1 (25.0) |
Pleural effusion | 1 (33.3) | 0 | 0 | 1 (33.3) | 0 | 0 |
Productive cough | 0 | 0 | 1 (33.3) | 1 (33.3) | 0 | 0 |
Pruritus | 1 (33.3) | 0 | 1 (33.3) | 0 | 0 | 0 |
Sepsis | 1 (33.3) | 1 (33.3) | 0 | 0 | 0 | 0 |
Sinus tachycarida | 1 (33.3) | 0 | 0 | 1 (33.3) | 0 | 0 |
Skin fissures | 0 | 0 | 0 | 0 | 1 (33.3) | 1 (25.0) |
Thrombocytopenia | 1 (33.3) | 0 | 0 | 0 | 0 | 1 (25.0) |
Weight decreased | 0 | 1 (33.3) | 0 | 0 | 1 (33.3) | 0 |
Pharmacokinetic properties
Dose, mg | AUC0–168 (μg h/mL) [CV%] | AUC0–∞ (μg h/mL) [CV%] | Cmax (μg/mL) [CV%] | Median Tmax (h) (range) | CL (mL/h) [CV%] | T1/2 (h) [CV%] |
---|---|---|---|---|---|---|
50 (n = 3) | 401.7 [31.4] | – | 15.0 [36.8] | 2.1 (2.0–5.1) | 130.9 [31.4] | – |
100 (n = 3) | 2542.0 [41.8] | 3316.4 [21.1] | 43.2 [20.4] | 5.0 (2.0–24.0) | 45.7 [50.9] | 38.4 [31.1] |
200 (n = 3) | 5914.3 [25.3] | 7350.1 [22.0] | 76.1 [11.8] | 5.0 (2.1–5.1) | 35.2 [23.1] | 75.1 [8.3] |
400 (n = 3) | 9174.3 [34.3] | 34,057.3 [110.6] | 118.7 [68.2] | 1.9 (1.1–5.0) | 47.9 [40.0] | 411.2 [133.9] |
600 (n = 3) | 14,279.7 [17.3] | 25,036.3 [22.3] | 157.7 [24.4] | 5.0 (2.0–5.0) | 42.9 [18.6] | 138.7 [10.5] |
800 (n = 4) | 21,059.2 [19.8] | 36,513.7 [23.8] | 234.0 [24.2] | 5.0 (5.0–24.0) | 39.1 [19.4] | 148.0 [37.7] |