A Phase 3, Global, Multi-Center, Double-Blind, Randomized, Efficacy Study of Zolbetuximab (IMAB362) Plus mFOLFOX6 Compared with Placebo Plus mFOLFOX6 as First-line Treatment of Subjects with Claudin (CLDN)18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
Clinical Trial Information
Trial Contact: De Leon, Ma Theresa; Donaldson, Karin M
IRB No: WT20.033.04
Protocol Abbrev: TRIO_SPOTLIGHT
Principal Investigator: Omar R. Kayaleh, MD
Phase: Drug: Phase III
Age Group: Adult
Secondary Protocol No: SPOTLIGHT 8951-CL-0301
Treatment: Zolbetuximab (Experimental Drug) Plus mFOLFOX6 Chemotherapy mFOLFOX6 as Treatment for Gastric and Gastroesophageal Junction Gastroesophageal (GEJ) Cancer
Therapies Involved: Chemotherapy
ClinicalTrials.gov ID: NCT03504397
To evaluate the efficacy of zolbetuximab plus mFOLFOX6 compared with placebo plus mFOLFOX6 (as first-line treatment) as measured by Progression Free Survival (PFS) in subjects with Claudin (CLDN)18.2 positive, human epidermal growth factor receptor 2 (HER2)–negative locally advanced unresectable or metastatic gastric and gastroesophageal junction (GEJ) adenocarcinoma
• Female subject eligible to participate if she is not pregnant (negative serum pregnancy test at screening; female subjects with elevated serum beta human chorionic gonadotropin and a demonstrated non-pregnant status through additional testing are eligible) and at least one of the following conditions applies:
◦Not a woman of child-bearing potential (WOCBP) OR
◦WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 6 months after the final study drug administration
• Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study drug administration.
• Female subject must agree not to donate ova starting at screening and throughout the study period, and for 6 months after the final study drug administration.
• A sexually active male subject with a female partner(s) who is of child-bearing potential must agree to use contraception during the treatment period and for at least 6 months after the final study drug administration.
• Male subject must agree not to donate sperm starting at screening and throughout the study period, and for 6 months after the final study drug administration.
• Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 6 months after the final study drug administration.
• Subject has histologically confirmed diagnosis of Gastric or GEJ adenocarcinoma.
• Subject has radiologically confirmed locally advanced unresectable or metastatic disease within 28 days prior to the first dose of study treatment.
• Subject has measurable disease according to RECIST 1.1 within 28 days prior to the first dose of study treatment. For subjects with only 1 measurable lesion and prior radiotherapy, the lesion must be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
• Subject's tumor expresses CLDN18.2 in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central immunohistochemistry (IHC) testing.
• Subject has a HER2-Negative tumor as determined by local or central testing on a gastric or GEJ tumor specimen.
• Subject has ECOG performance status 0 to 1.
• Subject has predicted life expectancy ≥ 12 weeks.
• Subject must meet all of the following criteria based on the centrally analyzed laboratory tests within 14 days prior to the first dose of study treatment. In case of multiple laboratory data within this period, the most recent data should be used to determine eligibility.
◦Hemoglobin (Hgb) ≥ 9 g/dL. NOTE: subject must not have received any growth factor or blood transfusions within 14 days prior to the hematology values obtained at screening. Subjects requiring transfusions to meet eligibility criteria are not eligible.
◦Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
◦Platelets ≥ 100 x 10^9/L
◦Albumin ≥ 2.5 g/dL
◦Total bilirubin < 1.5 x upper limit of normal (ULN)
◦Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN without liver metastases (or ≤ 5 x ULN if liver metastases are present)
◦Estimated creatinine clearance ≥ 30 mL/min
◦Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) ≤ 1.5 x ULN (except for subjects receiving anticoagulation therapy)