Bintrafusp alfa is a first-in-class bifunctional fusion protein that was designed for colocalized, simultaneous inhibition of two nonredundant immunosuppressive pathways, transforming growth factor-β (TGFβ) and programmed death-ligand 1 (PD-L1), within the tumor microenvironment. |
In this expansion cohort of a phase 1 study, bintrafusp alfa had a manageable safety profile and demonstrated clinical activity in Asian patients with pretreated, PD-L1–unselected esophageal squamous cell carcinoma. |
Along with the results of an expansion cohort of patients with advanced, post-platinum esophageal adenocarcinoma from a separate phase 1 study described in the accompanying article, further investigation of bintrafusp alfa in esophageal cancer is warranted. |
1 Background
2 Patients and Methods
2.1 Study Design and Participants
2.2 Treatment and Assessments
2.3 Endpoints
2.4 Exploratory Endpoints
2.5 Statistical Analysis
3 Results
3.1 Patient Demographics and Characteristics
Characteristic | N = 30 |
---|---|
Median age, years (range) | 60 (40–80) |
Sex, n (%) | |
Male Female | 26 (86.7) 4 (13.3) |
ECOG performance status, n (%) | |
0 1 | 9 (30.0) 21 (70.0) |
Number of prior anticancer therapy regimens, n (%) | |
1 2 ≥ 3 | 7 (23.3) 13 (43.3) 10 (33.3) |
Number of prior lines of therapy for locally advanced or metastatic disease, n (%) | |
0 1 ≥ 2 | 5 (16.7) 10 (33.3) 15 (50.0) |
Type of prior anticancer therapy for locally advanced or metastatic disease, n (%)a | |
Cytotoxic therapy Immunotherapy except anti-PD-(L)1 Other | 25 (83.3) 1 (3.3) 1 (3.3) |
Tumor cell PD-L1 expression, n (%)b | |
Positive Negative Not evaluable | 14 (46.7) 13 (43.3) 3 (10.0) |
3.2 Safety
Preferred term, n (%) | N = 30 | |
---|---|---|
Any grade | Grade 3/4 | |
TRAEs | ||
TRAE | 19 (63.3) | 7 (23.3) |
Maculopapular rash | 6 (20.0) | 1 (3.3) |
Rash | 5 (16.7) | 1 (3.3) |
Hypothyroidism | 5 (16.7) | 0 |
Interstitial lung disease | 3 (10.0) | 1 (3.3)a |
KA | 3 (10.0) | 0 |
Pruritus | 3 (10.0) | 0 |
Blood creatinine increased | 2 (6.7) | 0 |
Eczema | 2 (6.7) | 1 (3.3) |
Hyperthyroidism | 2 (6.7) | 0 |
Retinal hemorrhage | 2 (6.7) | 0 |
Amylase increased | 1 (3.3) | 1 (3.3) |
Blood creatine phosphokinase increased | 1 (3.3) | 1 (3.3)b |
Lichenoid keratosis | 1 (3.3) | 1 (3.3) |
Lip SCC | 1 (3.3) | 1 (3.3) |
Any AE of special interest | ||
Skin lesionsc | 4 (13.3) | 1 (3.3) |
Any irAE | 12 (40.0)d | 4 (13.3) |
Immune-related rash | 10 (33.3) | 2 (6.7) |
Immune-related thyroid disorders | 3 (10.0) | 0 |
Immune-related interstitial lung disease | 2 (6.7) | 1 (3.3)a |
Other irAEs | 1 (3.3) | 1 (3.3) |
3.3 Efficacy
Independent review committee | Investigator | |
---|---|---|
Confirmed best overall response, n (%) | ||
Complete response Partial response Stable disease Non-complete response/non-progressive disease Progressive disease Not evaluable | 0 3 (10.0) 3 (10.0) 3 (10.0) 18 (60.0) 3 (10.0) | 0 6 (20.0) 5 (16.7) 0 17 (56.7) 2 (6.7) |
Confirmed ORR, n (%) 95% CI | 3 (10.0) 2.1–26.5 | 6 (20.0) 7.7–38.6 |
DCR, n (%) 95% CI | 9 (30.0) 14.7–49.4 | 11 (36.7) (19.9–56.1) |
Median duration of response, months (range) | 7.0 (2.8–8.3+) | 7.0 (4.2+–11.1+) |
ORR by tumor cell PD-L1 expression, n/N (%)a | ||
Positive Negative Not evaluable | 3/14 (21.4) 0/13 (0) 0/3 (0) | 2/14 (14.3) 3/13 (23.1) 1/3 (33.3) |