Introduction
Materials/patients and methods
Pre-clinical pharmacology
Induction and activation of OCV-501-specific Th1 cells from peripheral blood mononuclear cells
CD8+ killer T cell activation by OCV-501-specific Th1 cell
HLA class II-restriction and cytolytic activity of OCV-501-specific Th1 clones
Clinical study
Study design
Patients
Drug administration
Safety and efficacy assessments in patients
Statistical analysis
Results
Pre-clinical pharmacology
Ex vivo induction and activation of OCV-501-specific helper T cells
HLA class II-restriction and cytolytic activity of OCV-501-specific Th1 clones
HLA class II | Formation of complexes with various HLA class II molecules (change in HPLC retention time : Δmin)a
| |||||
---|---|---|---|---|---|---|
Negative controlb
| Positive controlc
| OCV-501 | ||||
DRB1*04:05 | − | (0.021) | + | (0.461) | + | (0.470) |
DRB1*15:01 | − | (0.076) | + | (0.410) | + | (0.278) |
DRB1*15:02 | − | (0.001) | + | (0.298) | + | (0.371) |
DRB1*01:01 | − | (0.028) | + | (0.418) | + | (0.525) |
DRB1*08:03 | − | (0.007) | + | (0.412) | + | (0.538) |
DRB1*09:01 | − | (0.007) | + | (0.285) | + | (0.325) |
DRB4*01:01 | − | (0.034) | + | (0.132) | + | (0.180) |
Clinical trial
Dose | Subject ID | Classification of acute myeloid leukemia | Sex | Age (years) | HLA-DRB1 Genotype | ECOG PS | |
---|---|---|---|---|---|---|---|
Result 1 | Result 2 | Scorea
| |||||
0.3 mg | 001–0001 | Acute myeloid leukemia, not otherwise specified, AML without maturation | Female | 70 | 08:03 | 09:01 | 0 |
002 − 0001 | Acute myeloid leukemia, not otherwise specified, AML with maturation | Female | 62 | 04:05 | 04:06 | 0 | |
002–0002 | Acute myeloid leukemia, not otherwise specified, AML with minimal differentiation | Male | 69 | 13:02 | 15:01 | 0 | |
1.0 mg | 001–0002 | Acute myeloid leukemia, not otherwise specified, AML without maturation | Female | 65 | 01:01 | 15:02 | 0 |
002–0003 | Acute myeloid leukemia with recurrent genetic abnormalities, AML with t(8;21)(q22;q22); RUNX1-RUNX1T1 | Male | 71 | 04:05 | 09:01 | 0 | |
002–0004 | Acute myeloid leukemia with recurrent genetic abnormalities, AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11 | Female | 72 | 09:01 | 14:54 | 0 | |
3.0 mg | 001–0003 | Acute myeloid leukemia, not otherwise specified, AML with maturation | Male | 74 | 09:01 | 13:02 | 1 |
001–0004 | Acute myeloid leukemia, not otherwise specified, AML with maturation | Male | 73 | 04:05 | 04:06:01 | 0 | |
002–0005 | Acute myeloid leukemia, not otherwise specified, AML with maturation | Male | 62 | 04:07 | 15:02 | 0 |
Safety assessment
System organ class Preferred term | 0.3 mg | 1 mg | 3 mg | Total | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Grade 1 | Grade 2 | Grade 3–5 | Grade 1 | Grade 2 | Grade 3–5 | Grade 1 | Grade 2 | Grade 3–5 | |||
N = 3 |
N = 0 |
N = 0 |
N = 3 |
N = 0 |
N = 0 |
N = 3 |
N = 1 |
N = 0 |
N = 9 | ||
N
|
N
|
N
|
N
|
N
|
N
|
N
|
N
|
N
|
N
| (%) | |
General disorders and administration site conditions | 3 | 0 | 0 | 3 | 0 | 0 | 3 | 0 | 0 | 9 | (100.0) |
Injection site erythema | 3 | 0 | 0 | 3 | 0 | 0 | 3 | 0 | 0 | 9 | (100.0) |
Injection site induration | 2 | 0 | 0 | 2 | 0 | 0 | 3 | 0 | 0 | 7 | (77.8) |
Injection site mass | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | (11.1) |
Injection site pain | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | (11.1) |
Injection site pruritus | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 3 | (33.3) |
Investigations | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 2 | (22.2) |
Eosinophil count increased | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | (11.1) |
Lymphocyte count decreased | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | (11.1) |
Neutrophil count decreased | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | (11.1) |
White blood cell count decreased | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | (11.1) |
Musculoskeletal and connective tissue disorders | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | (11.1) |
Joint swelling | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | (11.1) |
Nervous system disorders | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | (22.2) |
Headache | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | (11.1) |
Hypoaesthesia | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | (11.1) |
Skin and subcutaneous tissue disorders | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | (11.1) |
Erythema | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | (11.1) |
Efficacy outcomes
Dose | Subject ID | Time point |
WT1 mRNA (copy/µg RNA) | Anti-OCV-501 antibody concentration (ng/mL) |
---|---|---|---|---|
0.3 mg | 001–0001 | Day 1 | <50 | Negative |
End of treatment | 75 | Negative | ||
002 − 0001 | Day 1 | 950 | Negative | |
End of treatment | 2400 | Negative | ||
002–0002 | Day 1 | <50 | Negative | |
End of treatment | 66 | Negative | ||
1.0 mg | 001–0002 | Day 1 | <50 | Negative |
End of treatment | 57 | Negative | ||
002–0003 | Day 1 | 64 | Negative | |
End of treatment | <50 | Negative | ||
002–0004 | Day 1 | 120 | Negative | |
End of treatment | 69 | Negative | ||
3.0 mg | 001–0003 | Day 1 | 150 | Negative |
End of treatment | 120 | Negative | ||
001–0004 | Day 1 | 340 | Negative | |
End of treatment | <50 | Negative | ||
002–0005 | Day 1 | 51 | Negative | |
End of treatment | 59 | Negative |