A Phase III, Multicentre, Randomised Controlled Study of Sonesitatug Vedotin in Combination With Capecitabine With or Without Rilvegostomig in First-Line Claudin18.2-Positive, HER2-Negative, Advanced/Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma (CLARITY-Gastric 02)
Study Description
The purpose of this study is to evaluate the efficacy and safety of sonesitatug vedotin in combination with capecitabine with or without rilvegostomig in first-line (1L) Claudin18.2 (CLDN18.2)-positive, human epidermal growth factor receptor 2 (HER2)-negative, gastric, gastroesophageal junction (GEJ), and esophageal adenocarcinoma.
Eligibility
Capable of giving signed informed consent
Participant must be 18 years or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the informed consent.
Previously untreated histologically documented unresectable, locally advanced, or metastatic gastric, GEJ, or distal esophagus (distal third of the esophagus) adenocarcinoma
Positive CLDN18.2 expression, as determined prospectively by central IHC testing
Confirmed PD-L1 CPS status by central IHC testing and ICI eligibility per investigator judgement is required to determine cohort eligibility as described below:
Cohort 1: PD-L1 positive as determined by central IHC testing and the participant is deemed ICI eligible per investigator judgement.
Cohort 2: PD-L1 negative as determined by central IHC testing OR the participant is ICI ineligible
ECOG performance status of 0 or 1 with no deterioration to > 1 over the previous 2 weeks prior to baseline at screening and prior to randomisation.
At least one lesion (measurable and/or non-measurable) that can be accurately assessed by the investigator based on RECIST 1.1.
Adequate organ and bone marrow function as specified in the protocol
Sex and contraceptive requirements
Known HER2-positive status
Significant or unstable gastric bleeding and/or untreated gastric ulcers.
Active or history of autoimmune or inflammatory disorders requiring systemic treatment with steroids or other immunosuppressive treatment or assessed by investigator as not appropriate to participate due to undue risk are excluded.
CNS pathology
Clinically significant pleural effusions or ascites and/or pleural effusions or ascites that require drainage, peritoneal shunt, or indwelling catheter/drain.
Require parenteral nutrition support due to gastric or gastrointestinal obstruction.
Peripheral neuropathy, sensory or motor, ≥ CTCAE Grade 2 at screening.
Persistent toxicities caused by previous anticancer therapy excluding alopecia, not yet improved to Grade ≤ 1 or baseline.
Cardiac abnormalities as outlined in the protocol
Uncontrolled diabetes or diabetic neuropathy within 3 months prior to randomisation.
Known partial or total DPD enzyme deficiency
