Introduction
Patients and methods
Selection of patients
Inclusion criteria
Exclusion criteria
Study design
Study outcomes
Safety assessments
Efficacy assessments
Statistical analyses
Results
Patient disposition and baseline characteristics
Patient characteristics | Cohort 1 (n = 3) | Cohort 2 (n = 3) | Expansion cohort (n = 13) | Cohort 1 + expansion cohort (n = 16) | Total (n = 19) |
---|---|---|---|---|---|
Demographic characteristics, mean ± SD | |||||
Age (years) | 73.3 ± 6.7 | 71.7 ± 5.9 | 71.3 ± 4.7 | 71.7 ± 4.9 | 71.7 ± 4.9 |
Weight (kg) | 67.7 ± 4.2 | 60.1 ± 3.1 | 62.3 ± 7.8 | 63.3 ± 7.5 | 62.8 ± 7.0 |
Height (cm) | 162.5 ± 4.8 | 165.8 ± 4.1 | 163.2 ± 4.2 | 163.1 ± 4.2 | 163.5 ± 4.2 |
Body mass index (kg/m2) | 25.6 ± 0.5 | 21.9 ± 1.1 | 23.4 ± 3.8 | 23.8 ± 3.2 | 23.5 ± 3.0 |
ECOG performance status at baseline, n (%) | |||||
0 | 3 (100.0) | 3 (100.0) | 11 (84.6) | 14 (87.5) | 17 (89.5) |
1 | 0 | 0 | 2 (15.4) | 2 (12.5) | 2 (10.5) |
Prior anticancer therapy/therapeutic procedures, n (%) | |||||
Prior therapeutic procedurea
| 1 (33.3) | 1 (33.3) | 2 (15.4) | 3 (18.8) | 4 (21.1) |
Prior diagnostic procedureb
| 3 (100.0) | 3 (100.0) | 13 (100.0) | 16 (100.0) | 19 (100.0) |
Prior systemic anti-cancer therapy | 3 (100.0) | 3 (100.0) | 13 (100.0) | 16 (100.0) | 19 (100.0) |
Prior radiotherapy | 0 | 1 (33.3) | 3 (23.1) | 3 (18.8) | 4 (21.1) |
Prior local anti-cancer therapyc
| 0 | 0 | 0 | 0 | 0 |
Baseline of tumor markers, mean ± SD | |||||
PSA (ng/mL) | 42.8 ± 25.1 | 669.6 ± 737.5 | 379.7 ± 505.5 | 316.5 ± 472.2 | 372.3 ± 496.2 |
ALP (U/L) | 198.0 ± 52.8 | 1354.0 ± 1697.8 | 1024.1 ± 1015.6 | 869.2 ± 967.6 | 945.7 ± 1049.0 |
Treatment exposure
Safety
TEAEs, n (%) | Cohort 1 (n = 3) | Cohort 2 (n = 3) | Expansion cohort (n = 13) | Cohort 1 + expansion cohort (n = 16) | Total (n = 19) |
---|---|---|---|---|---|
Drug-related TEAEsa
| |||||
Any | 1 (33.3) | 3 (100.0) | 7 (53.8) | 8 (50.0) | 11 (57.9) |
Worst grade, grade 5 (death) | 0 | 0 | 0 | 0 | 0 |
Worst grade, grade 3 or 4b
| 0 | 0 | 2 (15.4) | 2 (12.5) | 2 (10.5) |
Drug-related post treatment follow-up AEsc
| |||||
Any | 0 | 0 | 2 (15.4) | 2 (12.5) | 2 (10.5) |
Grade 5 (death) | 0 | 0 | 0 | 0 | 0 |
Grade 3 or 4b
| 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Long-term toxicityd
| 0 | 0 | 0 | 0 | 0 |
All drug-related TEAEs in treatment period, by MedDRA term (and by CTCAE where different) | |||||
Any | 1 (33.3) | 3 (100.0) | 7 (53.8) | 8 (50.0) | 11 (57.9) |
Anemia | 1 (33.3) | 0 | 3 (23.1) | 4 (25.0) | 4 (21.1) |
Constipation | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Diarrhea | 0 | 3 (100.0) | 0 | 0 | 3 (15.8) |
Lymphocytopenia (lymphocyte count decreased) | 0 | 0 | 2 (15.4) | 2 (12.5) | 2 (10.5) |
Thrombocytopenia (platelet count decreased) | 1 (33.3) | 0 | 2 (15.4) | 3 (18.8) | 3 (15.8) |
Leukopenia (white blood cells decreased) | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Bone pain | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Dysgeusia | 0 | 0 | 2 (15.4) | 2 (12.5) | 2 (10.5) |
Rash (rash acneiform) | 0 | 1 (33.3) | 0 | 0 | 1 (5.3) |
Grade 3 or grade 4 TEAEs by MedDRA (and by CTCAE where different), n (%) | Worst CTCAE grade | Cohort 1 (n = 3) | Cohort 2 (n = 3) | Expansion cohort (n = 13) | Cohort 1 + expansion cohort (n = 16) | Total (n = 19) |
---|---|---|---|---|---|---|
Anemia | Grade 3 | 0 | 0 | 4 (30.8) | 4 (25.0) | 4 (21.1) |
Nausea | Grade 3 | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Rectal stenosis | Grade 3 | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Infection (infections and infestations—other) | Grade 3 | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Lung infection (lung infection) | Grade 3 | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Lymphocytopenia (lymphocyte count decreased) | Grade 3 | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Leukopenia (white blood cells decreased) | Grade 3 | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Decreased appetite (anorexia) | Grade 3 | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Inadequate control of diabetes mellitus (glucose intolerance) | Grade 3 | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Hypocalcemia | Grade 3 | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Hypophosphatemia | Grade 3 | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Bone pain | Grade 3 | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Cancer pain (tumor pain) | Grade 3 | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Prostate cancer (neoplasms benign, malignant and unspecified, including cysts and polyps—other) | Grade 3 | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Renal impairment (renal and urinary disorders—other) | Grade 3 | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Treatment-emergent SAEs, by MedDRA (and by CTCAE where different), n (%) | Cohort 1 (n = 3) | Cohort 2 (n = 3) | Expansion cohort (n = 13) | Cohort 1 + expansion cohort (n = 16) | Total (n = 19) |
---|---|---|---|---|---|
Rectal hemorrhage | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Infection (infections and infestations—other) | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Lung infection (lung infection) | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Bone pain | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Prostate cancer (neoplasms benign, malignant and unspecified incl. cysts and polyps—other) | 0 | 0 | 1 (7.7) | 1 (6.3) | 1 (5.3) |
Efficacy
Markers | 12 weeks after treatment | End of treatment | ||||
---|---|---|---|---|---|---|
n
| Mean ± SD | Range |
n
| Mean ± SD | Range | |
PSA | 11 | 83.5 ± 124.5 | −32.4 to 423.8 | 16 | 182.0 ± 254.2 | −37.8 to 934.5 |
Bone markers | ||||||
Total ALP | 11 | −30.4 ± 23.6 | −69.1 to 12.1 | 16 | −27.7 ± 25.2 | −66.5 to 26.0 |
Bone ALP | 11 | −46.2 ± −18.7 | −78.0 to −10.5 | 16 | −48.2 ± 17.2 | −75.1 to −13.7 |
P1NP | 11 | −42.1 ± 25.0 | −71.2 to 9.7 | 16 | −29.5 ± 40.0 | −81.4 to 45.9 |
CTX-1 | 11 | −20.8 ± 24.1 | −66.7 to 0.0 | 16 | 35.9 ± 127.2 | −66.7 to 500.0 |
ICTP | 11 | 14.3 ± 38.3 | −12.8 to 116.0 | 16 | 69.2 ± 190.4 | −24.4 to 763.0 |