LBA3 - Tumor Treating Fields (TTFields) therapy plus XELOX chemotherapy for front line treatment of advanced unresectable gastroesophageal junction adenocarcinoma (GEJC) or gastric adenocarcinoma (GC): A multicenter phase II trial

Background

Tumor Treating Fields (TTFields) therapy is a locoregional, noninvasive treatment approved for glioblastoma and mesothelioma. TTFields, electric fields that disrupt cellular processes critical for cancer cell viability and tumor progression, are generated by a portable device, delivered by skin-placed arrays. In vitro data show synergistic cytotoxic effects with TTFields and chemotherapy in gastric cancer cells, warranting clinical investigation of TTFields therapy concomitant with chemotherapy in GC/GEJC.

Methods

EF-31/ZL-8301-001 (NCT04281576; 04/30/22 cutoff), a phase 2, single-arm, multicenter study evaluated first line TTFields therapy concomitant with XELOX (TTFields/XELOX) in adult patients with unresectable, locally advanced, or metastatic GC/GEJC, ECOG-PS 0–1, without prior systemic treatment. Patients received TTFields (150 kHz; NovoTTF-200T device) therapy for ≥ 18 h/day, and XELOX Q3W. Trastuzumab was permitted for HER-2+ tumors. Tumor evaluation (CT/MRI) was Q9W. The primary endpoint was investigator-assessed ORR (RECIST). Secondary endpoints included PFS, OS, disease control rate (DCR), duration of response (DOR), and safety.

Results

28 Chinese patients were enrolled; 26 had evaluable efficacy data. 54% had an ECOG-PS=1, and 77% had stage IV disease. 58% patients had poorly differentiated G3 histology; 6 (23%) patients received trastuzumab. ORR was higher with TTFields/XELOX (50%) vs historical controls (45%). DCR was 81% among patients. Median DOR, PFS, OS were 10.3 mo, 7.8 mo, and 12.2 mo, respectively. All cause AEs (>50%) were reduced platelets (57%); anemia, nausea, and neutropenia (all 54%). All skin AEs were mild/moderate. No serious TTFields-related AEs were reported.

Conclusions

First line TTFields/XELOX was well-tolerated, feasible, and showed clinical activity in patients with unresectable GC/GEJC. The improved ORR indicates synergistic activity, warranting confirmation in a Phase 3 pivotal study.

Clinical trial identification

NCT04281576.

Editorial acknowledgement

Editorial assistance under the direction of the authors was provided by Melissa Purves PhD, CMPP of Prime, UK, funded by Novocure.

Legal entity responsible for the study

Novocure Inc. and Zai Labs.

Funding

Novocure Inc.

Disclosure

K.O. Lam: Financial Interests, Institutional, Research Grant: Bayer, Roche, Taiho; Financial Interests, Institutional, Advisory Board, Honoraria: Amgen, Bayer, BMS, Daiichi Sankyo, Eli Lilly, Lintonpharm, Merck, MSD, Novartis, Roche, Sanofi-Aventis, Taiho. Y. Xu: Financial Interests, Personal, Full or part-time Employment: Zai Lab; Financial Interests, Personal, Stocks/Shares: Zai Lab. Y. Yang: Financial Interests, Personal, Full or part-time Employment: Zai Lab. G. Lavy-Shahaf: Financial Interests, Personal and Institutional, Full or part-time Employment, Employee of Novocure, Owned stock of held ownership interest, paid honoraria: Novocure. All other authors have declared no conflicts of interest.