Introduction
Materials and methods
Study design
Patients
Endpoints and assessments
Statistical analysis
Results
Phase I
Patients and treatment
MTD and DLTs
Safety
Phase II
Patients and treatment
Xe1000+Ev10+Ex25 (n = 70) | Ev10+Ex25 (n = 70) | Total (n = 140) | |
---|---|---|---|
Median age, years (range) | 58.5 (41–86) | 62.0 (42–84) | 60.0 (41–86) |
ECOG PS, n (%) | |||
0 | 45 (64.3) | 38 (54.3) | 83 (59.5) |
1 | 25 (35.7) | 31 (44.3) | 56 (40.0) |
2 | 0 | 1 (1.4) | 1 (0.7) |
Median time since diagnosis, months (range) | 63.4 (12.4–343.5) | 63.3 (8.3–256.6) | 63.3 (8.3–343.5) |
Metastatic sites at screening, n (%) | |||
1 | 18 (25.7) | 16 (22.9) | 34 (24.3) |
2 | 25 (35.7) | 27 (38.6) | 52 (37.1) |
≥ 3 | 27 (38.6) | 27 (38.6) | 54 (38.6) |
Visceral involvement, n (%) | |||
Yes | 53 (75.7) | 54 (77.1) | 107 (76.4) |
No | 17 (24.3) | 16 (22.9) | 33 (23.6) |
Bone metastases, n (%) | 47 (67.1) | 52 (74.3) | 99 (70.7) |
Lymph node metastases, n (%) | 33 (47.1) | 25 (35.7) | 58 (41.4) |
Prior hormone therapy, n (%) | 68 (97.1) | 69 (98.6) | 137 (97.9) |
Prior chemotherapy in metastatic setting, n (%) | 17 (24.3) | 18 (25.7) | 35 (25.0) |
Prior CDK 4/6 inhibitor treatment, n (%) | 0 | 2 (2.9) | 2 (1.4) |
Efficacy
PFS
Pre-specified subgroup analysis: visceral and non-visceral disease
Secondary and further endpoints
Xe1000+Ev10+Ex25 (n = 70) | Ev10+Ex25 (n = 70) | |
---|---|---|
Best overall response | ||
CR | 1 (1.4) | 0 |
PR | 4 (5.7) | 7 (10.0) |
Non-CR/non-PD, n (%) | 10 (14.3) | 8 (11.4) |
Non-CR/non-PD ≥ 24 weeks | 4 (5.7) | 3 (4.3) |
SD, n (%) | 28 (40.0) | 32 (45.7) |
SD ≥ 24 weeks | 4 (5.7) | 7 (10.0) |
PD, n (%) | 16 (22.9) | 14 (20.0) |
Not evaluable, n (%) | 11 (15.7) | 9 (12.9) |
OR, n (%) | 5 (7.1) | 7 (10.0) |
Odds ratio (95% CI) [P value]† | 0.70 (0.20–2.32) [P = 0.5598] | |
Median time to OR, months (range) | 3.7 (1.8–5.3) | 1.8 (1.6–7.2) |
Median duration of OR,‡ months (95% CI) | 5.6 (NC–NC) | NC (1.8–NC) |
Disease control, n (%) | 13 (18.6) | 17 (24.3) |
Odds ratio (95% CI) [P value]† | 0.70 (0.31–1.59) [P = 0.4008] | |
Median duration of disease control,‡ months (95% CI) | NC (9.2–NC) | 9.3 (9.0–NC) |
Safety
Patients, n (%) | Xe1000+Ev10+Ex25 (n = 70) | Ev10+Ex25 (n = 69) | ||
---|---|---|---|---|
Any AE | 70 (100.0) | 68 (98.6) | ||
Any grade ≥ 3 AE | 39 (55.7) | 31 (44.9) | ||
Any TRAE | 66 (94.3) | 66 (95.7) | ||
Any grade ≥ 3 TRAE | 31 (44.3) | 21 (30.4) | ||
Any serious AE | 15 (21.4) | 20 (29.0) | ||
Most common any-cause AEs | Any grade | Grade ≥ 3 | Any grade | Grade ≥ 3 |
Diarrhoea | 29 (41.4) | 1 (1.4) | 20 (29.0) | 1 (1.4) |
Mucosal inflammation | 27 (38.6) | 2 (2.9) | 21 (30.4) | 0 |
Stomatitis | 24 (34.3) | 4 (5.7) | 24 (34.8) | 3 (4.3) |
Nausea | 24 (34.3) | 0 | 16 (23.2) | 0 |
Rash | 23 (32.9) | 0 | 21 (30.4) | 0 |
Cough | 23 (32.9) | 1 (1.4) | 16 (23.2) | 2 (2.9) |
Asthenia | 21 (30.0) | 1 (1.4) | 24 (34.8) | 2 (2.9) |
Fatigue | 20 (28.6) | 0 | 17 (24.6) | 1 (1.4) |
Neutropenia | 20 (28.6) | 8 (11.4) | 11 (15.9) | 2 (2.9) |
Decreased appetite | 18 (25.7) | 1 (1.4) | 21 (30.4) | 0 |
Hyperglycaemia | 18 (25.7) | 4 (5.7) | 15 (21.7) | 3 (4.3) |
Headache | 17 (24.3) | 0 | 9 (13.0) | 0 |
Thrombocytopenia | 17 (24.3) | 4 (5.7) | 10 (14.5) | 1 (1.4) |
ALT increased | 16 (22.9) | 3 (4.3) | 10 (14.5) | 1 (1.4) |
Anaemia | 15 (21.4) | 2 (2.9) | 11 (15.9) | 2 (2.9) |
Vomiting | 14 (20.0) | 2 (2.9) | 13 (18.8) | 0 |
AST increased | 13 (18.6) | 3 (4.3) | 13 (18.8) | 0 |
Epistaxis | 13 (18.6) | 0 | 9 (13.0) | 1 (1.4) |
Platelet count decreased | 13 (18.6) | 1 (1.4) | 3 (4.3) | 0 |
Constipation | 13 (18.6) | 1 (1.4) | 6 (8.7) | 0 |
Pruritus | 13 (18.6) | 0 | 12 (17.4) | 0 |
Nasopharyngitis | 12 (17.1) | 0 | 6 (8.7) | 0 |
Hypophosphataemia | 11 (15.7) | 6 (8.6) | 8 (11.6) | 2 (2.9) |
Dysgeusia | 11 (15.7) | 0 | 10 (14.5) | 0 |
Dyspnoea | 9 (12.9) | 1 (1.4) | 17 (24.6) | 4 (5.8) |
Peripheral oedema | 5 (7.1) | 0 | 14 (20.3) | 0 |
Arthralgia | 4 (5.7) | 0 | 11 (15.9) | 0 |
Mouth ulceration | 3 (4.3) | 0 | 12 (17.4) | 0 |