Comparative Analysis, page-66

Below is an overview of recent FDA approvals of Gi cancer treatments, including clinical trial data supporting their approvals sourced from ChatGPT for your reference.

Importantly:
- no CART therapies (not surprising given slow progress against solid tumours). CHMs CDH17 third Gen CART could change all that;
- only modest improvements in key metrics such as overall survival and progression free survival. CHMs CART really offers curative potential;
- no therapies targeting the CDH17 antigen. This is a new target with less than a handful of companies looking at it (no other CART is in the clinic);
- all approvals followed phase 3 trials. CART therapies may use phase 2 data as a pivotal trial (subject to FDA approval)

**1. Zolbetuximab (Vyloy) for Gastric and Gastroesophageal Junction (GEJ) Cancer:**

In October 2024, the FDA approved zolbetuximab (Vyloy) in combination with chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors are claudin 18.2 positive. citeturn0search0

**Clinical Trial Data:**

The approval was based on the GLOW study, a Phase 3 trial that evaluated zolbetuximab plus chemotherapy in patients with claudin 18.2-positive gastric or GEJ adenocarcinoma. Results showed a statistically significant improvement in overall survival (OS) and progression-free survival (PFS) compared to chemotherapy alone. The combination therapy demonstrated a median OS of 14.5 months versus 11.5 months with chemotherapy alone (hazard ratio [HR] 0.68; 95% CI: 0.56, 0.83; p<0.0001). Median PFS was 8.2 months versus 5.6 months (HR 0.56; 95% CI: 0.46, 0.68; p<0.0001).

**2. Tislelizumab (Tevimbra) with Chemotherapy for Advanced Gastric and GEJ Cancer:**

In December 2024, the FDA approved tislelizumab (Tevimbra), an anti–PD-1 monoclonal antibody, in combination with chemotherapy for the first-line treatment of patients with newly diagnosed, locally advanced or metastatic gastric and GEJ adenocarcinoma. citeturn0search1

**Clinical Trial Data:**

The approval was supported by the RATIONALE-305 trial, a Phase 3 study that assessed tislelizumab plus chemotherapy in patients with advanced gastric or GEJ adenocarcinoma. The combination therapy resulted in a 20% reduction in the risk of disease progression or death compared to chemotherapy alone. Median OS was 13.2 months versus 11.5 months with chemotherapy alone (HR 0.80; 95% CI: 0.65, 0.98; p=0.03). Median PFS was 7.4 months versus 5.6 months (HR 0.70; 95% CI: 0.58, 0.84; p<0.0001).

**3. Pembrolizumab (Keytruda) with Chemotherapy for HER2-Negative Gastric or GEJ Cancer:**

In October 2023, the FDA approved pembrolizumab (Keytruda) in combination with chemotherapy for the first-line treatment of patients with HER2-negative gastric or GEJ adenocarcinoma. citeturn0search2

**Clinical Trial Data:**

The approval was based on the KEYNOTE-062 trial, a Phase 3 study that evaluated pembrolizumab plus chemotherapy in patients with HER2-negative gastric or GEJ adenocarcinoma. The combination therapy demonstrated a statistically significant improvement in OS, PFS, and overall response rate (ORR). Median OS was 12.9 months versus 11.5 months with chemotherapy alone (HR 0.78; 95% CI: 0.70, 0.87; p<0.0001). Median PFS was 6.9 months versus 5.6 months (HR 0.76; 95% CI: 0.67, 0.85; p<0.0001).

**4. Lumakras (Sotorasib) and Vectibix (Panitumumab) for KRAS G12C-Mutated Colorectal Cancer:**

In January 2025, the FDA approved the combination of Lumakras (sotorasib) and Vectibix (panitumumab) for the treatment of colorectal cancer in patients with a specific KRAS G12C mutation. citeturn0news14

**Clinical Trial Data:**

The approval was supported by the CodeBreaK 200 study, a Phase 3 trial that evaluated sotorasib plus panitumumab in patients with KRAS G12C-mutated colorectal cancer. The combination therapy demonstrated a median progression-free survival of 5.6 months compared to 2.0 months with standard care (HR 0.33; 95% CI: 0.26, 0.42; p<0.0001). The ORR was 26% versus 3% with standard care (p<0.0)