Abstract 2382
Background
Tislelizumab, an investigational anti-PD-1 antibody, 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. Previous reports showed tislelizumab was generally well tolerated and had antitumor activity in patients (pts) with advanced solid tumours, including UC.
Methods
This phase 2 clinical trial (CTR20170071) assessed the safety, tolerability, and efficacy of tislelizumab (200 mg Q3W) in Asian pts with PD-L1+ UC previously treated with ≥1 platinum-containing therapy. Prior treatment with a PD-(L)1 inhibitor was not allowed. During screening, archival tissue or fresh biopsy from all pts was sent to a central laboratory for PD-L1 testing via the VENTANA SP263 IHC assay. Patients were considered PD-L1+ if ≥ 25% of tumor or immune cells had PD-L1 expression. The primary efficacy endpoint was ORR (RECIST v1.1), assessed by an independent review committee (IRC). Secondary efficacy endpoints included DoR, PFS, and OS; AE incidence and severity were secondary safety endpoints.
Results
Between 04 Jul 2017 and 28 Feb 2019, 113 pts received tislelizumab for a median of 15 weeks and were followed up for a median of 8 mo. Urinary bladder (n = 51) and renal pelvis (n = 31) were common primary tumor sites. Of 104 evaluable pts, a confirmed objective response was observed in 24 pts (ORR=23%, 95% CI: 15.4, 32.4), including 8 CR and 16 PR per IRC assessment. Median DoR per IRC was not reached at the time of protocol-defined analysis; 19/24 (79%) responders had ongoing responses at data cutoff. Median PFS and OS were 2.1 and 9.8 mo, respectively. Anemia (27%), decreased appetite (19%), and pyrexia (17%) were the only TRAEs occurring in > 15% of pts; anemia (7%) was the only grade 3-4 TRAE occurring in ≥ 5% pts. Four pts experienced a grade 5 AE considered related to disease progression but also possibly related to treatment (hepatic failure, n = 2; respiratory arrest, n = 1; renal impairment, n = 1).
Conclusions
Tislelizumab was generally well tolerated and demonstrated clinical activity in pts with PD-L1+ UC.
Clinical trial identification
CTR20170071.
Editorial acknowledgement
Stephan Lindsey, PhD, at OPEN Health Medical Communications (Chicago, IL).
Legal entity responsible for the study
BeiGene, Ltd.
Funding
BeiGene, Ltd.
Disclosure
X. Qiu: Full / Part-time employment: BeiGene. L. Zhang: Full / Part-time employment: BeiGene. W. Shen: Full / Part-time employment: BeiGene. All other authors have declared no conflicts of interest.
Resources from the same session
5043 - Comprehensive results of a Phase Ib study with a HER2/neu B-cell peptide vaccine administered with cisplatin and 5-fluorouracil or capecitabine chemotherapy show safety, immunogenicity and clinical response in patients with HER2/Neu overexpressing advanced gastric cancer
Presenter: Ursula Wiedermann
Session: Poster Display session 3
Resources:
Abstract
4506 - Single intravenous preoperative administration of the oncolytic virus Pexa-Vec to prime anti-tumor immunity
Presenter: Adel Samson
Session: Poster Display session 3
Resources:
Abstract
1631 - Randomized phase 2 clinical trial of NY-ESO-1 protein vaccine combined with cholesteryl pullulan (CHP-NY-ESO-1) in resected esophageal cancer patients
Presenter: Shinichi Kageyama
Session: Poster Display session 3
Resources:
Abstract
4244 - T cell repertoire sequencing reveals dynamics of response to dendritic cell vaccine plus dasatinib for checkpoint blockade resistant metastatic melanoma
Presenter: Luca Quagliata
Session: Poster Display session 3
Resources:
Abstract
5791 - Ixovex, a novel oncolytic E1B-mutated adenovirus
Presenter: Mohiemen Anwar
Session: Poster Display session 3
Resources:
Abstract
4170 - Anti-CSPG4 DNA vaccination as a promising strategy for the treatment of CSPG4+ tumors: a comparative oncology trial
Presenter: Federica Riccardo
Session: Poster Display session 3
Resources:
Abstract
5780 - Antitumor activity, immunogenicity and safety of a novel PD-1 vaccine in combination with two chimeric HER-2 peptide vaccine in syngeneic Balb/c, C57Bl/6 models and in beagle dogs
Presenter: Pravin Kaumaya
Session: Poster Display session 3
Resources:
Abstract
5860 - Maternal immunization against ALK as a weapon to fight neuroblastoma
Presenter: Giuseppina Barutello
Session: Poster Display session 3
Resources:
Abstract
4720 - Phase 1 study evaluating safety, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of ABBV-428, first-in-class mesothelin (MSLN)-CD40 bispecific, in patients (pts) with advanced solid tumors
Presenter: Jason Luke
Session: Poster Display session 3
Resources:
Abstract
5717 - Anti-PD-L1/IL-15 fusion protein generates robust adaptive immune gene signatures in tumors leading to tumor inhibition and memory responses
Presenter: Stella Martomo
Session: Poster Display session 3
Resources:
Abstract