Introduction
Methods
Study design
Patients
Treatment and randomization
Endpoints and assessments
Statistical analysis
Results
Patients
Characteristic | Bemarituzumab-mFOLFOX6 (N = 77) | Placebo-mFOLFOX6 (N = 78) |
---|---|---|
Age | ||
Median (range), years | 60.0 (23–80) | 59.5 (33–84) |
≥ 65 years | 19 (24.7) | 25 (32.1) |
Male sex | 52 (67.5) | 59 (75.6) |
Race | ||
Asian | 45 (58.4) | 44 (56.4) |
Black | 0 | 1 (1.3) |
American Indian or Alaska Native | 0 | 1 (1.3) |
White | 30 (39.0) | 31 (39.7) |
Other | 2 (2.6) | 1 (1.3) |
Site of primary cancer | ||
Gastric adenocarcinoma | 66 (85.7) | 71 (91.0) |
Gastroesophageal junction adenocarcinoma | 11 (14.3) | 7 (9.0) |
Metastatic disease | 73 (94.8) | 66 (84.6) |
Tumor histology | ||
Diffuse | 28 (36.4) | 26 (33.3) |
Intestinal | 16 (20.8) | 15 (19.2) |
Mixed | 5 (6.5) | 12 (15.4) |
Unknown | 28 (36.4) | 25 (32.1) |
ECOG performance status | ||
0 | 25 (32.5) | 28 (35.9) |
1 | 52 (67.5) | 50 (64.1) |
Administration of a single dose of mFOLFOX6 before randomization | 35 (45.5) | 36 (46.2) |
Prior neoadjuvant or adjuvant therapy | 14 (18.2) | 13 (16.7) |
FGFR2b expression | ||
Overexpression by IHC regardless of ctDNA (2 + /3 + staining score in any tumor cell) | 73 (94.8) | 76 (97.4) |
IHC staining score of 2 + or 3 + in ≥ 10% of tumor cells regardless of ctDNA | 46 (59.7) | 52 (66.7) |
Amplification by ctDNA regardless of IHC | 12 (15.6) | 14 (17.9) |
Both overexpression by IHC and amplification by ctDNA | 8 (10.4) | 12 (15.4) |
Progression-free survival
Overall survival
Response rate
Variable | ITT set | FGFR2b ≥ 10% subgroup | ||
---|---|---|---|---|
Bemarituzumab-mFOLFOX6 (N = 77) | Placebo-mFOLFOX6 (N = 78) | Bemarituzumab-mFOLFOX6 (N = 46) | Placebo-mFOLFOX6 (N = 52) | |
Measurable disease at baseline | 66 (85.7) | 60 (76.9) | 41 (89.1) | 42 (80.8) |
Non-measurable disease at baseline | 11 (14.3) | 18 (23.1) | 5 (10.9) | 10 (19.2) |
Best overall response | ||||
Complete response | 4 (5.2) | 2 (2.6) | 2 (4.3) | 1 (1.9) |
Partial response | 33 (42.9) | 24 (30.8) | 24 (52.2) | 18 (34.6) |
Stable disease | 29 (37.7) | 38 (48.7) | 12 (26.1) | 20 (38.5) |
Progressive disease | 5 (6.5) | 6 (7.7) | 3 (6.5) | 5 (9.6) |
Not evaluable | 6 (7.8) | 8 (10.3) | 5 (10.9) | 8 (15.4) |
Objective response rate (ORR)a | 37 (48.1) | 26 (33.3) | 26 (56.5) | 19 (36.5) |
95% CIb | 36.5–59.7 | 23.1–44.9 | 41.1–71.1 | 23.6–51.0 |
Difference in ORR, (95% CI)b | 14.4 (-1.5–30.3) | 20 (0.6–39.4) | ||
Duration of responsec | ||||
Number of patients | 37 | 26 | ||
Median (95% CI), months | 11.9 (6.9–17.3) | 7.5 (4.3–13.8) |
Efficacy for patients in FGFR2b ≥ 10% subgroup
Subsequent therapies
Safety
Bemarituzumab-mFOLFOX6 (N = 76) | Placebo-mFOLFOX6 (N = 77) | |
---|---|---|
Any TEAE | 76 (100.0) | 76 (98.7) |
Serious TEAEs | 26 (34.2) | 28 (36.4) |
Grade ≥ 3 TEAEs | 63 (82.9) | 58 (75.3) |
TEAEs related to any study agent | 72 (94.7) | 73 (94.8) |
Grade ≥ 3 TEAEs related to any study agent | 57 (75.0) | 48 (62.3) |
TEAEs leading to discontinuation of bemarituzumab/placebo | 31 (40.8) | 4 (5.2) |
Deaths | 53 (69.7) | 54 (70.1) |
Fatal TEAEs | 5 (6.6) | 4 (5.2) |
Commonly reported TEAEs | Any grade | Grade ≥ 3 | Any grade | Grade ≥ 3 |
---|---|---|---|---|
Nausea | 37 (48.7) | 0 | 41 (53.2) | 3 (3.9) |
Neutrophil count decreased | 31 (40.8) | 23 (30.3) | 33 (42.9) | 28 (36.4) |
Diarrhoea | 31 (40.8) | 3 (3.9) | 24 (31.2) | 1 (1.3) |
Anaemia | 26 (34.2) | 7 (9.2) | 28 (36.4) | 11 (14.3) |
Decreased appetite | 23 (30.3) | 1 (1.3) | 29 (37.7) | 2 (2.6) |
Constipation | 23 (30.3) | 0 | 25 (32.5) | 1 (1.3) |
Vomiting | 23 (30.3) | 2 (2.6) | 24 (31.2) | 2 (2.6) |
Aspartate aminotransferase increased | 24 (31.6) | 5 (6.6) | 15 (19.5) | 2 (2.6) |
Abdominal pain | 18 (23.7) | 2 (2.6) | 20 (26.0) | 3 (3.9) |
Fatigue | 16 (21.1) | 1 (1.3) | 21 (27.3) | 3 (3.9) |
Asthenia | 20 (26.3) | 6 (7.9) | 16 (20.8) | 3 (3.9) |
Stomatitis | 26 (34.2) | 7 (9.2) | 10 (13.0) | 2 (2.6) |
Platelet count decreased | 14 (18.4) | 1 (1.3) | 21 (27.3) | 0 |
Alanine aminotransferase increased | 23 (30.3) | 2 (2.6) | 11 (14.3) | 1 (1.3) |
Peripheral sensory neuropathy | 15 (19.7) | 6 (7.9) | 15 (19.5) | 4 (5.2) |
Neutropenia | 15 (19.7) | 10 (13.2) | 13 (16.9) | 7 (9.1) |
White blood cell count decreased | 16 (21.1) | 5 (6.6) | 12 (15.6) | 5 (6.5) |
Dry eye | 21 (27.6) | 2 (2.6) | 5 (6.5) | 0 |
Weight decreased | 16 (21.1) | 0 | 10 (13.0) | 0 |
Pyrexia | 11 (14.5) | 0 | 14 (18.2) | 0 |
Neuropathy peripheral | 13 (17.1) | 3 (3.9) | 11 (14.3) | 1 (1.3) |
Paraesthesia | 13 (17.1) | 1 (1.3) | 10 (13.0) | 1 (1.3) |
Epistaxis | 17 (22.4) | 0 | 3 (3.9) | 0 |
Leukopenia | 9 (11.8) | 2 (2.6) | 9 (11.7) | 5 (6.5) |
Cough | 8 (10.5) | 0 | 8 (10.4) | 0 |
Dyspepsia | 7 (9.2) | 0 | 9 (11.7) | 1 (1.3) |
Pruritus | 8 (10.5) | 0 | 8 (10.4) | 0 |
Thrombocytopenia | 11 (14.5) | 1 (1.3) | 4 (5.2) | 1 (1.3) |
Hypoalbuminemia | 4 (5.3) | 0 | 10 (13.0) | 2 (2.6) |
Vision blurred | 13 (17.1) | 0 | 1 (1.3) | 0 |
Hypokalemia | 4 (5.3) | 2 (2.6) | 8 (10.4) | 3 (3.9) |
Keratitis | 11 (14.5) | 3 (3.9) | 1 (1.3) | 0 |
Mucosal inflammation | 8 (10.5) | 1 (1.3) | 4 (5.2) | 0 |
Punctate keratitis | 10 (13.2) | 4 (5.3) | 2 (2.6) | 0 |
Corneal disorders | 3 (3.9) | 3 (3.9) | 0 | 0 |
Cataract | 2 (2.6) | 2 (2.6) | 0 | 0 |
Corneal erosion | 2 (2.6) | 2 (2.6) | 0 | 0 |
Category | Bemarituzumab-mFOLFOX6 (N = 76) | Placebo-mFOLFOX6 (N = 77) |
---|---|---|
Any corneal AE | 51 (67.1) | 8 (10.4) |
Grade ≥ 3 corneal AEs | 21 (27.6) | 0 |
Time to onset of any-grade corneal AEs | ||
Number of patients | 51 | 8 |
Median (IQR), weeks | 16.9 (10.1–24.0) | 11.6 (7.7–16.6) |
Time to onset of ≥ grade 2 corneal AEs | ||
Number of patients | 37 | 2 |
Median (IQR), weeks | 23.7 (16.1–33.1) | 12.8 (9.0–16.6) |
Corneal disorders leading to drug discontinuation | 24 (31.6) | 0 |
Commonly reported corneal AEs | ||
Dry eye | 21 (27.6) | 5 (6.5) |
Keratitis | 12 (15.8) | 1 (1.3) |
Punctate keratitis | 11 (14.5) | 2 (2.6) |
Corneal epithelium defect | 9 (11.8) | 0 |
AE resolution category | ||
All corneal TEAEs resolved | 23 (30.3) | 3 (3.9) |
All corneal TEAEs resolved or downgraded to grade 1 | 12 (15.8) | 4 (5.2) |
Time to resolution of any-grade corneal AEs | ||
Number of patients | 27 | 2 |
Median (IQR), weeks | 24.4 (13.0–41.1) | 1.4 (0.9–2.0) |
Time to resolution/downgrading of grade ≥ 2 corneal AEs to grade 1 | ||
Number of patients | 22 | 1 |
Median (IQR), weeks | 20.3 (9.1–31.1) | 2.0 (2.0–2.0) |