Tislelizumab, an investigational monoclonal antibody with high affinity and specificity for PD-1, was engineered to minimize binding to FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. In prior reports, tislelizumab, as a single agent and in combination with various chemotherapies, was generally well tolerated and had antitumor activity in pts with advanced solid tumors. This phase 2 study (NCT03469557) assessed tislelizumab plus chemotherapy as first-line therapy in pts with inoperable, locally advanced, or metastatic GC/GEJC or ESCC.
Patients with GC/GEJC received tislelizumab (200 mg IV Q3W) + oxaliplatin (130 mg/m2 IV Q3W for ≤6 cycles) and capecitabine (1000 mg/m2, Days 1-15 orally BID Q3W); pts with ESCC received tislelizumab + cisplatin (80 mg/m2 IV Q3W for ≤6 cycles) and 5FU (800 mg/m2/d, Days 1-5 IV Q3W for ≤6 cycles). Response was assessed using RECIST v1.1, Kaplan-Meier analysis estimated survival, and adverse event (AE) monitoring examined safety/tolerability.
As of 31 Mar 2019, 30 pts with GC/GEJC and ESCC (n = 15 each) were enrolled. Median age was 61 yr; most pts were male (n = 25). Clinical responses were observed during treatment (Table). In pts with ESCC, treatment-emergent AEs (TEAEs) of grade ≥3 occurring in ≥ 2 pts were vomiting and dysphagia (n = 4 each), hyponatremia (n = 3), and anemia, leukopenia, fatigue, lung infection, and decreased weight (n = 2 each). No grade ≥3 TEAEs occurred in ≥ 2 pts with GC/GEJC. One pt with ESCC had a fatal AE (hepatic dysfunction) attributed to treatment by the investigator, but which may have been confounded by progressive disease and underlying hepatitis.Table:
|GC/GEJC (n = 15)||ESCC (n = 15)|
|PR, n (%)||7 (46.7)||7 (46.7)|
|SD, n (%)||3 (20.0)||5 (33.3)|
|PD, n (%)||1 (6.7)||0 (0.0)|
|Non-CR/non-PD, n (%)*||2 (13.3)||0 (0.0)|
|NE, n (%)||2 (13.3)||3 (20.0)|
|ORR, % (95% CI)||46.7 (21.3, 73.4)||46.7 (21.3, 73.4)|
|Median DoR, (95% CI)||NR (3.0, NR)||12.8 (3.5, 12.8)|
|Median PFS, mo (95% CI)||6.1 (3.8, NR)||10.4 (5.6, 15.1)|
|Median OS, mo (95% CI)||NR (7.0, NR)||NR (5.6, NR)|
|Median follow-up, mo (95% CI)||15.4 (14.7, 17.2)||13.0 (12.3, 14.0)|
Patients who have non-target lesions at baseline.
Abbreviations: CI, confidence interval; CR, complete response; DoR, duration of response; ESCC, esophageal squamous cell carcinoma; GC/GEJC, gastric/gastroesophageal junction cancer; mo, month; NE, not evaluable; NR, not reached; ORR, objective response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease.
Tislelizumab plus chemotherapy was generally well tolerated and antitumor activity was observed in pts with advanced GC/GEJC or ESCC.
Clinical trial identification
Writing and editorial support for this abstract was provided by Agnieszka Laskowski, PhD, and Elizabeth Hermans, PhD, of OPEN Health Medical Communications (Chicago, IL).
Legal entity responsible for the study
BeiGene Co., Ltd., Beijing, China.
BeiGene (Beijing) Co., Ltd., Beijing, China.
X. Li: Full / Part-time employment: BeiGene (Beijing) Co., Ltd. Y. Li: Full / Part-time employment: BeiGene (Beijing) Co., Ltd. X. Wang: Full / Part-time employment: BeiGene (Beijing) Co., Ltd. S. Yang: Full / Part-time employment: BeiGene (Beijing) Co., Ltd. All other authors have declared no conflicts of interest.