Introduction
Methods
Study design and treatment
Eligibility criteria
Study objectives
Pharmacokinetic analysis
Statistical methods
Results
Patients
Dose, mg/kg | n | Reason for withdrawal | |
---|---|---|---|
Dose escalation (n = 26) | Not dosed | 1 | Other (patient enrolled but not included in the safety population) |
3.2 | 6 | PD (n = 2), AE (n = 2), symptomatic deterioration (n = 2) | |
6 | 3 | PD (n = 2), death (n = 1) | |
10 | 4 | PD (n = 3), symptomatic deterioration (n = 1) | |
15 | 3 | PD (n = 2), withdrew consent (n = 1) | |
20 | 5 | PD (n = 2), withdrew consent (n = 1), symptomatic deterioration (n = 2) | |
40/20 | 4 | PD (n = 3), symptomatic deterioration (n = 1) | |
Dose expansion (n = 18) | 40/20 | 18 | PD (n = 14), investigator decision (n = 1), symptomatic deterioration (n = 3) |
Characteristic | Dose escalation (n = 25) | Dose expansion (n = 18) |
---|---|---|
Median age, years (range) | 62 (29‒81) | 57 (47‒71) |
Median body weight, kg (range) | 75 (44‒119)a | 71 (55‒140) |
Sex, n (%) | ||
Female | 12 (48) | 15 (83) |
Tumor type, n (%) | ||
Colorectal cancerb | 10 (40) | 3 (17) |
Breast cancer | 1 (4) | 8 (44) |
Ovarian cancerc | 1 (4) | 4 (22) |
Lung cancer | 3 (12) | 1 (6) |
Bladder cancer | 0 | 1 (6) |
Melanoma | 2 (8) | 0 |
Squamous cell carcinomad | 2 (8) | 0 |
Pancreatic cancer | 1 (4) | 0 |
Esophageal cancer | 1 (4) | 0 |
Mucoepidermoid carcinomae | 1 (4) | 0 |
Peritoneal cancer | 1 (4) | 0 |
Prostate cancer | 1 (4) | 0 |
Thymic carcinoma | 1 (4) | 0 |
Urethra carcinoma | 0 | 1 (6) |
Safety
Dose escalation
TEAE, n (%) | Dose escalation (n = 25) | Dose expansion (n = 18) | ||
---|---|---|---|---|
All grades | Grade ≥ 3 | All grades | Grade ≥ 3 | |
At least one TEAE | 25 (100) | 12 (48) | 18 (100) | 9 (50) |
Nausea | 12 (48) | 0 | 8 (44) | 1 (6) |
Diarrhea | 10 (40) | 0 | 6 (33) | 2 (11) |
Fatigue | 10 (40) | 3 (12) | 11 (61) | 2 (11) |
Anemiaa | 9 (36) | 1 (4) | 6 (33) | 0 |
Rash | 8 (32) | 0 | 2 (11) | 0 |
Decreased appetite | 7 (28) | 0 | 5 (28) | 0 |
Hyperglycemia | 7 (28) | 0 | 3 (17) | 0 |
Vomiting | 6 (24) | 0 | 6 (33) | 1 (6) |
Hypokalemia | 6 (24) | 1 (4) | 5 (28) | 1 (6) |
Hypoalbuminemia | 6 (24) | 0 | 2 (11) | 0 |
Hypomagnesemia | 6 (24) | 0 | 1 (6) | 0 |
Back pain | 6 (24) | 0 | 0 | 0 |
Hypocalcemia | 5 (20) | 0 | 1 (6) | 0 |
Increased alkaline phosphatase | 5 (20) | 0 | 0 | 0 |
Abdominal pain | 4 (16) | 1 (4) | 3 (17) | 0 |
Dehydration | 4 (16) | 1 (4) | 3 (17) | 1 (6) |
Dyspepsia | 4 (16) | 0 | 1 (6) | 0 |
Increased AST | 4 (16) | 0 | 0 | 0 |
Decreased weight | 3 (12) | 0 | 6 (33) | 0 |
Dyspnea | 3 (12) | 1 (4) | 4 (22) | 2 (11) |
Dysuria | 3 (12) | 0 | 2 (11) | 0 |
Hyponatremia | 3 (12) | 1 (4) | 1 (6) | 0 |
Constipation | 3 (12) | 0 | 1 (6) | 0 |
Stomatitis | 3 (12) | 0 | 1 (6) | 0 |
Disease progression | 3 (12) | 3 (12) | 1 (6) | 1 (6) |
Edema peripheral | 3 (12) | 1 (4) | 1 (6) | 1 (6) |
Dizziness | 3 (12) | 0 | 1 (6) | 1 (6) |
Pain in extremities | 3 (12) | 1 (4) | 0 | 0 |
Hypotension | 3 (12) | 1 (4) | 0 | 0 |
Headache | 2 (8) | 0 | 2 (11) | 0 |
Muscle spasms | 2 (8) | 0 | 2 (11) | 0 |
Musculoskeletal pain | 1 (4) | 0 | 3 (17) | 0 |
Prolonged activated partial thromboplastin time | 1 (4) | 1 (4) | 2 (11) | 1 (6) |
Asthenia | 1 (4) | 0 | 2 (11) | 0 |
Cough | 1 (4) | 0 | 2 (11) | 0 |
Decreased ejection fraction | 1 (4) | 0 | 2 (11) | 0 |
Flank pain | 1 (4) | 0 | 2 (11) | 1 (6) |
Exertional dyspnea | 0 | 0 | 5 (28) | 1 (6) |
Urinary tract infection | 0 | 0 | 4 (22) | 0 |
Lymphopenia | 0 | 0 | 2 (11) | 0 |
Pyrexia | 0 | 0 | 2 (11) | 0 |
Thrombocytopenia | 0 | 0 | 2 (11) | 0 |
Decreased potassium | 0 | 0 | 2 (11) | 0 |
Dose expansion
Safety with 40/20 mg/kg dose
Pharmacokinetics of seribantumab
Selection of RP2D
Efficacy
Best response | Dose escalation (n = 25), n (%) | Dose expansion (n = 18), n (%) |
---|---|---|
Overall response | 0 | 0 |
Complete response | 0 | 0 |
Partial response | 0 | 0 |
Stable disease | 6 (24) | 7 (39) |
Progressive disease | 11 (44) | 8 (44) |