Abstract 1518P
Background
Zani, an anti-HER2 bispecific antibody, targets two distinct extracellular domains of HER2 and has shown preliminary antitumor activity and tolerability, with chemo, in pts with HER2+ GC/GEJC. These are updated results from the phase Ib/II study (NCT04276493) for zani plus chemo and TIS, an anti-PD-1 monoclonal antibody. Duration of response is reported for the first time.
Methods
Cohort 2 of this open-label study included pts with untreated, unresectable, locally advanced/metastatic HER2+ GC/GEJC. Cohort 2a received zani 30 mg/kg intravenously (IV), Cohort 2b received zani 1800 mg IV (weight <70 kg) or 2400 mg IV (weight ≥70 kg), each with TIS 200 mg IV every 3 weeks. Both cohorts also received standard capecitabine-oxaliplatin (CAPOX). Primary endpoints were safety and investigator (INV)-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included INV-assessed progression-free survival (PFS), duration of response, and disease control rate.
Results
As of 22 Nov 2022, 33 pts (median age 64 years [range: 29-80]) were assigned to Cohort 2a (n=19) or 2b (n=14). Overall, 13 (39.4%) pts remained on treatment. Confirmed ORR was 75.8% (95% CI: 57.7, 88.9); median PFS was 16.7 months (95% CI: 8.2, NE). Efficacy data are presented in the table. All pts had ≥1 treatment-related adverse event (TRAE), and 22 (66.7%) had grade ≥3 TRAEs. Serious TRAEs occurred in 11 (33.3%) pts; TRAEs leading to treatment discontinuation occurred in two (6.1%) pts; and TRAEs leading to death occurred in two (6.1%) pts.
Table: 1518P
Cohort 2a (n=19) | Cohort 2b (n=14) | Overall (N=33) | |
Median follow-up, months | 19.1 | 18.0 | 18.2 |
Best overall response a , n (%) | |||
Complete response | 1 (5.3) | 0 (0.0) | 1 (3.0) |
Partial response | 14 (73.7) | 10 (71.4) | 24 (72.7) |
Stable disease | 4 (21.1) | 4 (28.6) | 8 (24.2) |
ORR a , n (%) (95% CI) | 15 (78.9) (54.4, 93.9) | 10 (71.4) (41.9, 91.6) | 25 (75.8) (57.7, 88.9) |
DCR a , n (%) (95% CI) | 19 (100.0) (82.4, 100.0) | 14 (100.0) (76.8, 100.0) | 33 (100.0) (89.4, 100.0) |
Median DoR, months (95% CI) | 15.4 (4.9, NE) | NE (7.4, NE) | 22.8 (7.4, NE) |
Median PFS, months (95% CI) | 8.3 (5.6, NE) | NE (8.8, NE) | 16.7 (8.2, NE) |
a Confirmed. DCR, disease control rate; DoR, duration of response; NE, not estimable; ORR, objective response rate; PFS, progression-free survival.
Conclusions
Zani plus TIS and CAPOX produced durable, promising antitumor activity with encouraging PFS as 1L therapy for pts with HER2+ GC/GEJC. Safety was consistent with previous findings. A phase III trial (NCT05152147) evaluating this regimen is ongoing.
Clinical trial identification
NCT04276493.
Editorial acknowledgement
Medical writing support, under the direction of the authors, was provided by Emily Finn, MSc, of Ashfield MedComms, an Inizio company, and was funded by BeiGene, Ltd.
Legal entity responsible for the study
BeiGene, Ltd.
Funding
BeiGene, Ltd.
Disclosure
K. Lee: Financial Interests, Personal, Advisory Board: BMS (Korea), Bayer (Korea), Daiichi Sankyo (Korea), Merck Sharp & Dohme (Korea), Metafines, Vifor pharma (Korea), Astellas (Korea); Financial Interests, Personal, Invited Speaker: Boryung Co.; Financial Interests, Institutional, Local PI: ABL Bio, ALX Oncology, Amgen, Arcus Biosciences, Astellas Pharma, AstraZeneca, BeiGene, Bolt therapeutics, Daiichi Sankyo, Exelixis, Genexine, Green Cross Corp, InventisBio, LSK BioPharma, Leap therapeutics, MacroGenics, MedPacto, Merck KGaA, Merck Sharp & Dohme, Oncologie, Ono pharmaceutical, Y-Biologics, Pfizer, Pharmacyclics, Seagen, Taiho Pharmaceutical, Trishula Therapeutics, Zymeworks; Non-Financial Interests, Leadership Role, SMC chair of ASPEN-06 study: ALX Oncology. M. Jung: Financial Interests, Advisory Role: Cartexell Inc. D. Oh: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Genentech/Roche, Merck, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, BMS/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences, IQVIA, MSD; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. P. Zhou, Y. Bao: Financial Interests, Full or part-time Employment: BeiGene; Financial Interests, Stocks/Shares: BeiGene. Y. Kang: Financial Interests, Personal, Advisory Board: ALX Oncology, Zymeworks, Amgen, Novartis, MacroGenics, Daehwa, Blueprint, Surface Oncology, BMS, Merck, Roche, LISCure. All other authors have declared no conflicts of interest.
Resources from the same session
1478P - Circulating pre-treatment T-Cell receptor repertoire as a predictive biomarker in non-small cell lung cancer patients treated with pembrolizumab
Presenter: Elin Gray
Session: Poster session 21
1479P - Association between high baseline low density neutrophils and resistance to immunotherapy in untreated non-small cell lung cancer: Molecular characterization of low-density neutrophils
Presenter: Hugo Arasanz
Session: Poster session 21
1480P - Integrating the on-treatment mGPS improves prognostic accuracy of imaging-based staging in patients with non-small-cell lung cancer (NSCLC) treated with immune-checkpoint inhibitors
Presenter: Jonas Saal
Session: Poster session 21
1481P - Singular immune-related adverse events and efficacy outcomes of immune checkpoint inhibitors in advanced non-small cell lung cancer
Presenter: Jose Miguel Jurado García
Session: Poster session 21
1482P - Multicenter pharmacokinetic study of pembrolizumab for non-small cell lung cancer in elderly adults aged over 75 years
Presenter: Jun Sakakibara-Konishi
Session: Poster session 21
1483P - Challenge of systemic first-line treatment of elderly lung cancer patients
Presenter: Konstantinos Ferentinos
Session: Poster session 21
1484P - Impact of concomitant KRAS/STK11 or KRAS/KEAP1 mutations on response to immune checkpoint inhibition in NSCLC: A real-world data analysis
Presenter: Louisa Hempel
Session: Poster session 21
1485P - Systemic inflammatory index dynamics at 6 weeks as an early surrogate for clinical benefit in patients with NSCLC and PD-L1≥50% expression treated with pembrolizumab: Data from the real-life practice
Presenter: Magdalena Knetki-Wroblewska
Session: Poster session 21
1486P - Treatment patterns and real-world clinical outcomes of metastatic non-small cell lung cancer patients in the immunotherapy era
Presenter: Sarah Sharman Moser
Session: Poster session 21
1487P - Real-world efficacy and safety of anlotinib in combination with PD-1/PD-L1 inhibitors as first-line or second-line treatment in advanced non-small cell lung cancer: Updated results
Presenter: Qi-Ming Wang
Session: Poster session 21