Health-related quality-of-life (HRQoL) results from the FAST study: A phase II trial of epirubicin, oxaliplatin, and capecitabine with or without IMAB362 in patients with advanced CLDN18.2+ gastric and gastroesophageal junction adenocarcinoma.

Abstract

54 Background: In the FAST study, IMAB362 (loading dose 800 mg/m2 then 600 mg/m2 d1 qd21) plus EOX (epirubicin 50 mg/m2 and oxaliplatin 130 mg/m2 d1, and capecitabine 625 mg/m2 bid) was compared with EOX alone in patients with advanced/metastatic gastric (GA), gastroesophageal (GE), and gastroesophageal junction (GEJ) adenocarcinoma. The FAST study exhibited a clinically relevant benefit in PFS and OS with a manageable safety profile in patients treated with IMAB362. Here we present the HRQoL results from the FAST study. Methods: CLDN18.2-positive patients (intermediate/strong membrane staining in ≥40% of cells) with advanced/metastatic GA/GE/GEJ adenocarcinoma were randomized 1:1 to first-line EOX for a maximum of 8 cycles with or without 600 mg/m2 q3w IMAB362, which after 8 cycles could be continued as monotherapy until disease progression (DP). The EORTC QLQC30 and a gastric cancer specific measure EORTC STO22 were collected at baseline (BL), Cycle 5, end of EOX therapy (EOT) and post-EOT every 12 weeks until DP. Change from BL in EORTC scores over 8 cycles of EOX treatment were analyzed using mixed model repeated measures. Time to deterioration in HRQoL was defined as time from randomization to first minimally clinically important difference (MCID) decline in each HRQoL domain. Results: The HRQoL analysis included 74 EOX and 68 IMAB362 + EOX per protocol patients. There were no significant differences in mean changes from BL in EORTC QLQC30 Global Health Status/QoL Score and STO22 Total Score across the 8 cycles of treatment with EOX. The QLQC30 Nausea and Vomiting domain showed a statistical difference (p = 0.0108) in favor of EOX-only. The median time to first HRQoL MCID deterioration for the QLQC30 Global Health Status was 8.6 mo for EOX + IMAB362 and 6.0 mo for EOX alone (p = 0.008). For patients who remained on IMAB362 post EOT, HRQoL improved from BL. Conclusions: HRQoL was maintained for a longer duration in pts with advanced/metastatic GA/GE/GEJ adenocarcinoma who received EOX + IMAB362 therapy vs EOX alone. HRQoL post EOT was improved for EOX + IMAB362 therapy vs EOX alone. Clinical trial information: NCT01630083.

Comparison of Claudin 18.2 expression in primary tumors and lymph node metastases in Japanese patients with gastric adenocarcinoma

“…In these patients, zolbetuximab, combined with chemotherapy, prolonged overall and progression-free survival over chemotherapy alone with acceptable safety and tolerability (25–28). Furthermore, in a subpopulation of patients with high CLDN18.2 expression (≥2+ staining intensity in ≥70% tumor cells), the observed antitumor activity was pronounced (29). In addition, health-related quality-of-life was maintained for a longer duration in patients who received EOX + zolbetuximab therapy compared with EOX alone (29).…”

“…Furthermore, in a subpopulation of patients with high CLDN18.2 expression (≥2+ staining intensity in ≥70% tumor cells), the observed antitumor activity was pronounced (29). In addition, health-related quality-of-life was maintained for a longer duration in patients who received EOX + zolbetuximab therapy compared with EOX alone (29).…”

Characterization of zolbetuximab in pancreatic cancer models

“…Zolbetuximab is a first-in-class mAb that specifically binds to the tight junction protein CLDN18.2 and has shown promising antitumor activity in patients with gastric and GEJ cancers. [7][8][9]24 In these nonclinical studies, zolbetuximab effected potent PC cell lysis in vitro by inducing ADCC and CDC. ADCC was more pronounced and affected more cell lines than CDC.…”

“…Clinical data of the antitumor activity of zolbetuximab in CLDN18.2-expressing GC and GEJ cancer have been promising, [7][8][9]24 which prompted investigations into the potential of zolbetuximab as a therapeutic agent for CLDN18.2-expressing PC as well. Our findings from this nonclinical study support the notion that zolbetuximab can be a therapeutic antibody not only for GC, but also for several other CLDN18.2-expressing solid tumors, such as PC.…”

“…8 Furthermore, health-related quality of life was maintained for a longer duration in patients who received zolbetuximab plus chemotherapy compared with chemotherapy alone. 9 In pancreatic cancer (PC), CLDN18.2 is aberrantly expressed with a prevalence of 60-90% reported in pancreatic ductal adenocarcinoma, the most common form of PC. [10][11][12] Aberrantly expressed CLDN18.2 appeared in precancerous lesions, indicating it may be valuable as an early marker of malignant transformation.…”