Vyloy (zolbetuximab-clzb)

Identifying practice barriers and proactively addressing them can result in a more rapid adoption of new therapies. This study identified 4 major challenges to the adoption of the novel targeted agent, zolbetuximab, in the community practice setting: limited awareness of clinical trial data, inadequate biomarker testing infrastructure, uncertainty in identifying optimal patient populations, and access barriers related to cost and insurance coverage. By implementing strategies identified from this study, we hope to accelerate and improve future adoption to innovative treatments in the community oncology setting, ultimately improving patient outcomes.

Real-world implementation of zolbetuximab is complicated by cumbersome administration times, short drug stability, extended observation time, and difficult tolerability. This report describes our experience in implementing zolbetuximab in clinical practice and provides an extensive drug evaluation.

Efficacy and safety data support randomized evaluation of zolbetuximab plus chemoimmunotherapy in patients with CLDN18.2-positive and PD-L1-positive mG/GEJ adenocarcinoma in the ongoing phase 3 LUCERNA study. ClinicalTrials.gov: NCT03505320 .

P3, N=500, Recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Dec 2029 --> Sep 2028 | Trial primary completion date: Dec 2029 --> Sep 2028

Its expression was rarely observed in other histological types of lung cancer. CLDN18.2 is frequently expressed in IMAs but rarely in other major lung cancer subtypes, suggesting that zolbetuximab may represent a promising targeted therapy for IMA.

We performed [89Zr]Zr-zolbetuximab immuno-PET imaging to quantify and localized CLDN18.2 expression in vivo, comparing uptake with [89Zr]Zr-trastuzumab in matched human epidermal growth factor receptor 2-positive patient-derived xenograft models. These findings outline a clinically relevant roadmap for CLDN18.2 radiotheranostics in which imaging enables patient selection and dosimetry, therapy delivers targeted tumor control, and rational combinations with chemotherapy or immunotherapy may further extend efficacy. Ultimately, this approach could make antibody-based radiopharmaceuticals a transformative modality in gastric cancer.

The target population for these recommendations is patients with unresectable locally advanced, advanced, or metastatic gastroesophageal cancer. Results from testing for actionable biomarkers should be available as soon as possible to inform treatment decision making. Immunotherapy with doublet chemotherapy is recommended for patients with proficient mismatch repair (pMMR)/microsatellite stable (MSS) human epidermal growth factor receptor 2 (HER2)-negative gastroesophageal adenocarcinoma or squamous cell carcinoma and PD-L1 expression ≥1; patients with higher PD-L1 expression are more likely to benefit from immunotherapy. Zolbetuximab is recommended for patients with gastroesophageal adenocarcinoma, PD-L1 <1, and positive CLDN18.2 expression. Patients with dual PD-L1 and CLDN18.2 positivity should engage in shared decision making, considering the factors outlined in the guideline. Doublet chemotherapy alone is recommended for patients who are not positive for actionable biomarkers or are not considered candidates for targeted therapy or immunotherapy. For patients with pMMR/MSS HER2-positive gastric/gastroesophageal junction (GEJ) adenocarcinoma, trastuzumab and doublet chemotherapy is recommended; for patients with PD-L1 expression ≥1, the addition of pembrolizumab is recommended. Immunotherapy alone or with doublet chemotherapy is recommended for patients with mismatch repair deficient/microsatellite instability-high gastroesophageal cancer. Second-line therapy options include ramucirumab with paclitaxel, trastuzumab deruxtecan for HER2-positive gastric/GEJ adenocarcinoma, and immunotherapy for PD-L1 ≥1 esophageal squamous cell carcinoma after first-line combination chemotherapy without immunotherapy.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

P3, N=2130, Recruiting, AstraZeneca

CLDN18.2 has become a major new target in gastric cancer targeted therapy. Its clinical trials and development are advancing quickly, with various types of drugs available. In the future, more released data may make treatment strategies better and give new treatment options to gastric cancer patients.