Gastric

A Phase 2/3 Interventional Study Of PF-08634404 In Combination With Chemotherapy In Treatment-Naïve Participants With Locally Advanced Or Metastatic Gastric, Gastroesophageal Junction, Or Esophageal Adenocarcinoma

MOA: PF-08634404 is a recombinant anti-PD-1 and anti-VEGF human mAb

Key Eligibility Criteria:

• Histologically or cytologically confirmed gastric, GEJ, or esophageal adenocarcinoma that is locally advanced unresectable or metastatic
• No prior systemic therapy for advanced or metastatic disease
• Subjects should have PD-L1 tumor expression (TAP ≥1% or CPS ≥1) and HER2-negative status based on local testing results
• Subjects with squamous cell or undifferentiated gastroesophageal cancer are excluded
• Subjects with prior exposure to anti-VEGF therapy or cancer immunotherapy, including but not limited to anti-PD-1/PD-L1 therapy are excluded

A Multicenter, randomized, open label, Phase 3 Trial of Trastuzumab Deruxtecan (ENHERTU®) plus chemotherapy plus or minus Pembrolizumab versus chemotherapy plus Trastuzumab plus or minus Pembrolizumab as first line treatment in participants with unresectable, locally advanced or metastatic HER2-postive Gastric or GEJ cancer. (Destiny- Gastric05) (Trial of Trastuzumab Deruxtecan (ENHERTU®) plus chemotherapy plus or minus Pembrolizumab versus chemotherapy plus trastuzumab plus or minus Pembrolizumab in first line metastatic HER2-positive gastric or GEJ cancer) (DS8201-724)

MOA: Trastuzumab deruxtecan (TDXd) is a HER2- directed ADC

Key Eligibility Criteria:

• Previously untreated, unresectable, locally advanced or metastatic HER2-positive gastric or GEJ cancer
• Centrally determined tumor PD-L1 CPS
  • Main Cohort: PD-L1 CPS ≥1
  • Exploratory Cohort: PD-L1 CPS <1
• Must provide a tumor sample for tissue-based IHC staining
• At least 1 target measurable lesion on CT or MRI
• Subjects with prior exposure to HER2-targeted therapy are excluded
• Subjects with known DPD enzyme deficiency are excluded

D702AC00001: A Randomized, Phase III Study of Rilvegostomig in Combination with Fluoropyrimidine and Trastuzumab Deruxtecan versus Trastuzumab, Chemotherapy, and Pembrolizumab for the First line Treatment of HER2-positive Gastric Cancer. (ARTEMIDE-Gastric01)

MOA: Rilvegostomig is a bispecific antibody with an engineered triple-mutant Fc domain targeting PD-1 and TIGIT.

Key Eligibility Criteria:

• Previously untreated, unresectable, locally advanced or metastatic gastric or GEJ cancer
• HER2-positive (IHC 3+ or IHC 2+ ISH-positive) on a tumor biopsy
• Central laboratory confirmed PD-L1 CPS ≥ 1 by PD-L1 expression
• Subjects with lack of physiological integrity of the upper gastrointestinal tract are excluded
• Subjects with known partial or total DPD enzyme deficiency are excluded