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1
Department of Medical Oncology, Monash Health, Melbourne, Victoria, Australia sophia.frentzas@monashhealth.org.
2
Faculty of Medicine, Nursing and Health Sciences and School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia.
3
Chris O'Brien Lifehouse, School of Medicine, University of Sydney, Sydney, New South Wales, Australia.
4
BeiGene (Shanghai) Ltd, Shanghai, China.
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BeiGene USA, Inc, San Mateo, California, USA.
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Linear Clinical Research and the University of Western Australia, Nedlands, Western Australia, Australia.
1
Department of Medical Oncology, Monash Health, Melbourne, Victoria, Australia sophia.frentzas@monashhealth.org.
2
Faculty of Medicine, Nursing and Health Sciences and School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia.
3
Chris O'Brien Lifehouse, School of Medicine, University of Sydney, Sydney, New South Wales, Australia.
4
BeiGene (Shanghai) Ltd, Shanghai, China.
5
BeiGene USA, Inc, San Mateo, California, USA.
6
Linear Clinical Research and the University of Western Australia, Nedlands, Western Australia, Australia.
Ociperlimab, a novel, humanized monoclonal antibody (mAb), binds to T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) with high affinity and specificity. Tislelizumab is an anti-programmed cell death protein 1 mAb. We report results from a phase I, first-in-human, dose escalation study evaluating the safety, pharmacokinetics (PK), and preliminary antitumor activity of ociperlimab plus tislelizumab in patients with advanced solid tumors.
Eligible patients previously treated with standard systemic therapy, or for whom treatment was not available or tolerated, received ociperlimab intravenously on Cycle (C) 1 Day (D) 1 and tislelizumab 200 mg intravenously on C1 D8. If tolerated, patients received ociperlimab plus tislelizumab 200 mg sequentially on D29 and every 3 weeks (Q3W) thereafter until discontinuation. Dose escalation for ociperlimab was planned with four dose levels (50 mg, 150 mg, 450 mg, and 900 mg) according to a 3+3 design. An additional dose level of ociperlimab 1800 mg was also assessed. Primary endpoints were safety, determination of the maximum tolerated (or administered) dose, and the recommended phase II dose (RP2D). Secondary endpoints included overall response rate (ORR), duration of response (DoR), disease control rate (DCR) (Response Evaluation Criteria in Solid Tumors version 1.1), PK, and biomarker analysis.
At data cut-off (September 29, 2022), 32 patients had received ≥1 dose of ociperlimab plus tislelizumab 200 mg Q3W. The maximum administered dose was ociperlimab 1800 mg plus tislelizumab 200 mg Q3W. The median age of enrolled patients was 59.5 years (range: 31-79). Most patients (96.9%) experienced ≥1 treatment-emergent adverse event (TEAE); 62.5% of patients experienced ≥grade 3 TEAEs and 50.0% of patients experienced serious TEAEs. No dose limiting toxicity events were reported. The maximum tolerated dose was not reached. The RP2D was ociperlimab 900 mg plus tislelizumab 200 mg Q3W. Overall, ORR was 10.0%, median DoR was 3.6 months, and DCR was 50.0%.
Competing interests: SF reports: advisory board or Data Safety Monitoring Board positions with Ambrax, Akesobio, and MSD; leadership or fiduciary roles with Monash Partners Comprehensive Cancer Consortium Precision Oncology Steering Committee, Victorian Comprehensive Cancer Center Accelerating Novel Therapies Steering Committee, and BeiGene, Ltd.; sponsorship and funding to Monash Health; honoraria from Amgen; consultancy fees from Akesobio and MSD. SK reports: speaker fees from Roche, MSD, Bristol Myers Squibb, Pfizer, AstraZeneca, and Specialised Therapeutics; advisory board income from Takeda, Pfizer, Roche, Boehringer, Eli Lilly, MSD, and Specialised Therapeutics; research grants from AstraZeneca. RG reports: employment by BeiGene, Ltd. HZ reports: employment by BeiGene, Ltd.; stock or stock options in BeiGene, Ltd. AR reports: employment by BeiGene, Ltd; stock or stock options in BeiGene, Ltd. NB reports: employment by BeiGene, Ltd.; stock or stock options in BeiGene, Ltd. LdlHP reports: employment by BeiGene, Ltd.; stock or stock options with BeiGene, Ltd. WT reports: employment by BeiGene, Ltd.; stock or stock options with BeiGene, Ltd. TM reports: advisory board/committee meeting positions with GlaxoSmithKline Australia Pty Ltd., AstraZeneca Australia, Takeda Pharmaceuticals Australia Pty Ltd., Novartis Pharmaceuticals Australia Pty Ltd., Bristol-Myers Squibb; educational speaker/chairperson for company meetings at Bristol Myers Squibb; consultancy services for Eisai.
Best change from baseline in target lesion sum of diameters (efficacy evaluable analysis set). Data cut-off: September 29, 2022. Measured per investigator assessment. Of the 30 patients that were efficacy-evaluable, 27 patients had measurable target lesions pre/post dose. The efficacy-evaluable analysis set included all patients who received ≥1 dose of study drugs, had evaluable disease at baseline, and ≥1 evaluable postbaseline tumor response assessment, unless any clinical PD or death occurred before the first postbaseline tumor assessment. PD, PR, and SD represent best change from baseline. *PD-L1 TC≥1%;
†
PD-L1 TC<1%;
‡
Did not receive prior anticancer therapy;
§
Received prior anticancer therapy. GC/GEJC, gastric/gastroesophageal junction cancer; non-sq, non-squamous; NPC, nasopharyngeal cancer; NSCLC, non-small cell lung cancer; PD, progressive disease; PD-L1, programmed death-ligand 1; PR, partial response; SD, stable disease; sq, squamous; TC, tumor cells.
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