Introduction
Materials and methods
Study design
Choice of starting dose
Patient eligibility
Study objectives and assessments
Statistical analyses
Results
Baseline characteristics
Characteristics | Phase 1 (n = 32) | Sitravatinib 120 mg phase 1b (n = 62) | Sitravatinib 150 mg phase 1b (n = 99) | Overall (n = 193) |
---|---|---|---|---|
Age, median (range) years | 62.0 (27–85) | 65.0 (43–87) | 67.0 (36–84) | 65.0 (27–87) |
Male, n (%) | 14 (43.8) | 32 (51.6) | 54 (54.5) | 100 (51.8) |
Race, n (%) | ||||
White | 24 (75.0) | 33 (53.2) | 78 (78.8) | 135 (69.9) |
Asian | 2 (6.3) | 20 (32.3) | 11 (11.1) | 33 (17.1) |
African American | 1 (3.1) | 6 (9.7) | 5 (5.1) | 12 (6.2) |
Other | 5 (15.6) | 3 (4.8) | 5 (5.1) | 13 (6.7) |
ECOG PS, n (%) | ||||
0 | 16 (50.0) | 24 (38.7) | 23 (23.2) | 63 (32.6) |
1 | 16 (50.0) | 33 (53.2) | 70 (70.7) | 119 (61.7) |
2 | 0 | 5 (8.1) | 6 (6.1) | 11 (5.7) |
Primary diagnosis, n (%) | ||||
NSCLC | 3 (9.4) | 25 (40.3) | 28 (28.3)a | 56 (29.0) |
Head and neck cancer | 0 | 1 (1.6) | 1 (1.0) | 2 (1.0) |
RCC | 3 (9.4) | 9 (14.5) | 29 (29.3) | 41 (21.2) |
Hormone-refractory prostate cancer | 3 (9.4) | 3 (4.8) | 10 (10.1) | 16 (8.3) |
Otherb | 23 (71.9) | 24 (38.7) | 31 (31.3) | 78 (40.4) |
Prior therapy, n (%) | ||||
Systemic | 31 (96.9) | 56 (90.3) | 93 (93.9) | 180 (93.3) |
Radiotherapy | 17 (53.1) | 30 (48.4) | 55 (55.6) | 102 (52.8) |
Surgery | 27 (84.4) | 35 (56.5) | 79 (79.8) | 141 (73.1) |
Number of prior systemic regimens, n (%) | ||||
Median (range) | 4 (1–10) | 3 (1–18) | 3 (1–11) | 3 (1–18) |
1 | 1 (3.1) | 12 (19.4) | 13 (13.1) | 26 (13.5) |
2 | 6 (18.8) | 14 (22.6) | 20 (20.2) | 40 (20.7) |
3 | 3 (9.4) | 11 (17.7) | 28 (28.3) | 42 (21.8) |
4 | 8 (25.0) | 9 (14.5) | 13 (13.1) | 30 (15.5) |
5+ | 13 (40.6) | 10 (16.1) | 19 (19.2) | 42 (21.8) |
DLTs in Phase 1
Safety
Patients who experienced TRAEs, n of patients (%) | Phase 1 (n = 32) | Sitravatinib 120 mg phase 1b (n = 62) | Sitravatinib 150 mg phase 1b (n = 99) | Overall (n = 193) |
---|---|---|---|---|
Any TRAE | 24 (75.0) | 58 (93.5) | 92 (92.9) | 174 (90.2) |
Grade ≥ 3 | 10 (31.3) | 32 (51.6) | 61 (61.6) | 103 (53.4) |
Serious | 3 (9.4) | 5 (8.1) | 22 (22.2) | 30 (15.5) |
Leading to discontinuation | 2 (6.3) | 7 (11.3) | 17 (17.2) | 26 (13.5) |
Leading to treatment modification | 12 (37.5) | 42 (67.7) | 66 (66.7) | 120 (62.2) |
Leading to death | 0 | 0 | 1 (1.0) | 1 (0.5) |
Most common TRAEs (≥ 10% of the population) by Preferred Term | Any grade | Grade ≥ 3 | Any grade | Grade ≥ 3 | Any grade | Grade ≥ 3 | Any grade | Grade ≥ 3 |
---|---|---|---|---|---|---|---|---|
Hypertension | 8 (25.0) | 5 (15.6) | 24 (38.7) | 11 (17.7) | 46 (46.5) | 24 (24.2) | 78 (40.4) | 40 (20.7) |
Diarrhea | 8 (25.0) | 2 (6.3) | 31 (50.0) | 4 (6.5) | 59 (59.6) | 14 (14.1) | 98 (50.8) | 20 (10.4) |
Fatigue | 13 (40.6) | 1 (3.1) | 21 (33.9) | 6 (9.7) | 49 (49.5) | 7 (7.1) | 83 (43.0) | 14 (7.3) |
PPE syndrome | 4 (12.5) | 1 (3.1) | 13 (21.0) | 6 (9.7) | 22 (22.2) | 4 (4.0) | 39 (20.2) | 11 (5.7) |
Nausea | 6 (18.8) | 0 | 14 (22.6) | 0 | 38 (38.4) | 5 (5.1) | 58 (30.1) | 5 (2.6) |
Vomiting | 6 (18.8) | 0 | 9 (14.5) | 0 | 31 (31.3) | 5 (5.1) | 46 (23.8) | 5 (2.6) |
ALT increased | 2 (6.3) | 0 | 15 (24.2) | 1 (1.6) | 18 (18.2) | 2 (2.0) | 35 (18.1) | 3 (1.6) |
Decreased appetite | 7 (21.9) | 0 | 17 (27.4) | 1 (1.6) | 27 (27.3) | 1 (1.0) | 51 (26.4) | 2 (1.0) |
AST increased | 2 (6.3) | 0 | 14 (22.6) | 0 | 20 (20.2) | 2 (2.0) | 36 (18.7) | 2 (1.0) |
Stomatitis | 3 (9.4) | 0 | 11 (17.7) | 1 (1.6) | 14 (14.1) | 1 (1.0) | 28 (14.5) | 2 (1.0) |
Weight decreased | 2 (6.3) | 0 | 7 (11.3) | 0 | 18 (18.2) | 2 (2.0) | 27 (14.0) | 2 (1.0) |
Proteinuria | 2 (6.3) | 0 | 11 (17.7) | 2 (3.2) | 9 (9.1) | 0 | 22 (11.4) | 2 (1.0) |
Rash | 4 (12.5) | 0 | 6 (9.7) | 2 (3.2) | 11 (11.1) | 0 | 21 (10.9) | 2 (1.0) |
Hypothyroidism | 3 (9.4) | 0 | 14 (22.6) | 0 | 16 (16.2) | 0 | 33 (17.1) | 0 |
Dysphonia | 2 (6.3) | 0 | 12 (19.4) | 0 | 13 (13.1) | 0 | 27 (14.0) | 0 |
Abdominal pain | 0 | 0 | 8 (12.9) | 0 | 14 (14.1) | 0 | 22 (11.4) | 0 |
Constipation | 2 (6.3) | 0 | 11 (17.7) | 0 | 9 (9.1) | 0 | 22 (11.4) | 0 |
Dry mouth | 4 (12.5) | 0 | 7 (11.3) | 0 | 10 (10.1) | 0 | 21 (10.9) | 0 |
Dizziness | 2 (6.3) | 0 | 6 (9.7) | 0 | 12 (12.1) | 0 | 20 (10.4) | 0 |
PK and PD analyses
Clinical activity
Overall (n = 161) | NSCLC with molecular alterations (n = 53) | Non-squamous NSCLC with prior CPI experience (n = 24) | |
---|---|---|---|
ORR, n (%) | 19 (11.8) | 7 (13.2) | 1 (4.2) |
CR | 0 | 0 | 0 |
PR | 19 (11.8) | 7 (13.2) | 1 (4.2) |
SD | 88 (54.7) | 30 (56.6) | 12 (50.0) |
PD | 28 (17.4) | 8 (15.1) | 5 (20.8) |
NEa | 26 (16.1) | 8 (15.1) | 6 (25.0) |
DoR, responders, n | 19 | 7 | 1 |
6-month KM estimate, % (95% CI) | 71.3 (44.0, 87.0) | 28.6 (4.1, 61.2) | 100 (100, 100) |
Median, months (95% CI) | 8.2 (4.3, 16.6) | 3.0 (1.8, 10.2) | 10.2 (NE, NE) |
PFS | |||
6-month KM estimate, % (95% CI) | 37.5 (29.2, 45.9) | 32.2 (19.2, 46.0) | 24.8 (7.8, 46.6) |
Median, months (95% CI) | 4.3 (3.1, 5.6) | 4.3 (2.9, 5.7) | 2.9 (1.5, 4.9) |
OS | |||
12-month KM estimate, % (95% CI) | 41.3 (32.7, 49.6) | 47.6 (32.4, 61.3) | 36.8 (16.5, 57.5) |
Median, months (95% CI) | 10.7 (9.9, 11.9) | 11.6 (6.6, 18.2) | 5.2 (2.4, 33.8) |