As ESMO Asia 2023 is approaching, prominent pharmaceutical industry leaders such as AstraZeneca, Amgen, Merck, Astellas Pharma, BeiGene, and others are all geared up for the upcoming conference. They are ready to showcase data readouts and conclusive analyses on a global scale as well as in the Asia-specific region. This content highlights crucial abstracts in gastrointestinal tumors that are expected to make a strong impact, generating considerable interest throughout the event.

The incidence of gastroesophageal junction cancer is on the rise. Owing to the high prevalence of H. pylori infection, certain dietary practices, smoking habits, and strong alcohol intake, gastric cancer is highly prevalent in Asian countries. 

Gastrointestinal Cancer Highlights

• Abstract Number – 129O
• Abstract Type - Proffered Paper Session
• Indication – Resectable gastric and gastroesophageal junction cancer (GC/GEJC)

Title: Pathological complete response (pCR) to durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) in resectable gastric and gastroesophageal junction cancer (GC/GEJC): Interim results of the global, Phase III MATTERHORN study

Executive Summary – The Phase III MATTERHORN trial revealed a substantial improvement in pathologic complete response (pCR) by adding IMFINZI (durvalumab) into perioperative FLOT therapy in patients with resectable early-stage gastric and gastroesophageal junction cancers. Additionally, this approach exhibited a well-tolerated safety profile as well.

Main Content: IMFINZI (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumor's immune-evading tactics and releasing the inhibition of immune responses. MATTERHORN, a global Phase III trial, evaluated IMFINZI as a perioperative treatment for patients with resectable Stage II-IVA gastric and gastroesophageal cancers. A total of 474 patients were randomized to each treatment group. Baseline characteristics were evenly distributed between the groups, with 19% of patients in each arm enrolled in Asia. Interim analysis was conducted after all randomized patients underwent or were precluded from surgery. 

The addition of IMFINZI to FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) regimen resulted in a significant increase in pathological complete response (pCR) compared to placebo (19% vs. 7%), with a combined pCR/near-complete response rate of 27% for IMFINZI exceeding the 14% observed with placebo. Surgery and resection rates were comparable between IMFINZI and placebo. The use of IMFINZI showed notable down staging and downsizing effects. The safety profile remained consistent, and adverse event rates were similar between the two groups. These findings support the potential of combining immunotherapy and chemotherapy in early-stage treatment for gastric and gastroesophageal junction cancers. 

• Abstract Number – 91MO
• Abstract Type - Mini Oral Session
• Indication – Metastatic colorectal cancer

Title: Sotorasib plus panitumumab versus standard-of-care for chemorefractory KRAS G12C-mutated metastatic colorectal cancer (mCRC): CodeBreak 300 Phase III study

Executive Summary – In the Phase III (CodeBreaK 300) study exploring a KRASG12C inhibitor combined with an anti-EGFR antibody in mCRC, sotorasib-panitumumab combination not only demonstrated a clinically significant advantage in PFS but also showed favorable outcomes in key secondary endpoints. Notably, superior outcomes were observed with the higher dose of sotorasib.

Main Content: The CodeBreaK 300 trial investigated the combination of sotorasib, a KRASG12C inhibitor, and panitumumab, an anti-EGFR antibody, in patients with chemorefractory KRAS G12C-mutated mCRC. Participants were randomly assigned to three groups: one receiving 960 mg of sotorasib with panitumumab, another receiving 240 mg of sotorasib with panitumumab, and a third with the investigator's choice between trifluridine, tipiracil, and regorafenib. 

The study revealed enhanced progression-free survival (PFS) at both 240 mg (3.9 months) and 960 mg (5.6 months) dosage levels in the sotorasib-panitumumab arms. The 960 mg combination achieved a 26.4% objective response rate, while the 240 mg combination showed a 5.7% response rate. Conversely, the investigator's choice arm had a 0% objective response rate. Overall survival (OS) data was immature at the data cutoff. Grade ≥3 treatment-related adverse events (TRAEs) occurring in ≥5% of patients. Importantly, no fatal TRAEs were reported in any arm. The combination of sotorasib and panitumumab demonstrated superior efficacy compared to the treatment selected by the investigator and emerges as a potential new standard-of-care therapy for previously treated, KRASG12C-mutated metastatic colorectal cancer.

• Abstract Number – 130O
• Abstract Type - Proffered Paper Session
• Indication – HER2+ Metastatic Gastric Or Gastroesophageal Junction (mG/GEJ) Adenocarcinoma

Title: The Phase III, randomized, double-blind, placebo-controlled KEYNOTE-811 study of pembrolizumab plus trastuzumab and chemotherapy for HER2+ metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma

Executive Summary – The interim analysis showed that pembrolizumab combined with trastuzumab and chemotherapy notably enhanced progression-free survival (PFS) and improved objective response rate (ORR) in patients with unresectable HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma, particularly in those with PD-L1 combined positive score (CPS) ≥1. These results support considering this regimen as a standard option for tumors that are positive for both HER2 and PD-L1.

Main Content: KEYTRUDA (pembrolizumab) plus standard of care (HERCEPTIN [trastuzumab] plus chemotherapy) has been granted accelerated approval by the FDA for the treatment of HER2-positive metastatic gastric or gastro-oesophageal junction (G/GEJ) adenocarcinoma, based on the prior analysis of Phase III KEYNOTE-811 trial that demonstrated an objective response rate (ORR) of 74% versus 52% in placebo arm in the initial 264 patients. Its continued approval hinges on positive confirmatory data. At the ESMO Asia 2023, results of a pre-specified interim analysis were presented. Dual primary endpoints were PFS or OS. 

In the first-line setting, the combination of pembrolizumab with standard of care (SOC) demonstrated a notable enhancement in progression-free survival (PFS) compared to placebo plus SOC for all patients, with a median PFS of 10 months versus 8.1 months. This improvement was also observed in patients with a PD-L1 combined positive score ≥1, showing a median PFS of 10.8 months versus 7.2 months at a median follow-up of 38.5 months. Overall survival (OS) was prolonged with pembrolizumab plus standard of care compared to placebo plus SOC with durations of 20.0 months versus 16.8 months for all patients and 20.0 months versus 15.7 months for those with a PD-L1 combined positive score ≥1. However, since the predetermined criteria for statistical significance was not achieved, the OS assessment proceeded to its final analysis. Additionally, the objective response rate was higher with pembrolizumab plus SOC compared to placebo plus SOC (73% vs. 60%). These results substantiate the benefit of combination therapy in a patient population with a high symptom burden, where any positive response to treatment could lead to a substantial improvement in quality of life.

• Abstract Number – 139MO
• Abstract Type - Mini Oral Session
• Indication – Advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC)

Title: Tislelizumab (TIS) plus chemotherapy (Chemo) vs placebo (PBO) plus chemo as first-line (1L) treatment of advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC): Final analysis results of the RATIONALE-305 study

Executive Summary – The final analysis of the Phase III RATIONALE 305 trial showcased a significant improvement in overall survival (OS) when tislelizumab was combined with chemotherapy as a first-line treatment in patients with advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC). 

Main Content: Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody, with high affinity and binding specificity against PD-1. The drug in combination with chemotherapy previously demonstrated significant OS benefits as 1L treatment in patients with advanced GC/GEJC at a pre-specified interim analysis of the PD-L1-positive population in the global Phase III RATIONALE-305 study. During ESMO Asia 2023, the outcomes from the final analysis in the intent-to-treat (ITT) population were unveiled.

The findings emphasized a notable enhancement in OS within the intent-to-treat (ITT) population, favoring the tislelizumab arm over the placebo arm, with a median OS of 15 months compared to 12.9 months, respectively. Furthermore, the combination of tislelizumab and chemotherapy exhibited an increased objective response rate (ORR) (47.3% vs. 40.5%) and a longer median duration of response (mDoR) (8.6 months vs. 7.2 months) compared to placebo plus chemotherapy alone. The median progression-free survival (PFS) for the tislelizumab group was 6.9 months. These results, along with positive findings, reinforce earlier data in the high PD-L1 expression group and contribute to the increasing body of evidence supporting the potential of tislelizumab in assisting patients with advanced gastric or gastroesophageal junction cancer.

• Abstract Number – 134MO 
• Abstract Type - Mini Oral Session
• Indication – Locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) Adenocarcinoma

Title: Updated efficacy and safety results from Phase III GLOW study evaluating zolbetuximab + CAPOX as first-line (1L) treatment for patients with claudin-18 isoform 2-positive (CLDN18.2+), HER2−, locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma

Executive Summary – The Phase III GLOW trial revealed consistent and significant improvements in both progression-free survival (PFS) and overall survival (OS) with zolbetuximab plus CAPOX in patients with CLDN18.2+, HER2−, locally advanced unresectable, or metastatic/gastroesophageal junction adenocarcinoma, without the emergence of new safety concerns. 

Main Content:  As of the June 2023 data cutoff, in the Phase III GLOW trial, 507 patients underwent randomization in a 1:1 ratio to receive either zolbetuximab plus CAPOX or placebo plus CAPOX. The study successfully achieved its primary endpoint, demonstrating a median progression-free survival (PFS) of 8.3 months with zolbetuximab plus CAPOX compared to 6.8 months with placebo plus CAPOX. Additionally, the key secondary endpoint of overall survival (OS) was also met, revealing a median OS of 14.3 and 12.2 months with and without zolbetuximab, respectively. The predominant treatment-emergent adverse events (TEAEs) associated with zolbetuximab plus CAPOX included occurrences of nausea, vomiting, and decreased appetite. The incidence of serious TEAEs was comparable between the two arms.

These results further confirm the survival benefits observed in the Phase III SPOTLIGHT study for the same patient pool, where the combination of zolbetuximab with mFOLFOX6 demonstrated significantly prolonged PFS (11.0 months) and OS (18.2 months). Together, these studies support the consideration of biomarker testing for tumor expression of CLDN18.2 and the use of zolbetuximab as a first-line treatment in combination with chemotherapy as a new potential standard of care in this biomarker-selected patient population.

List of Abstracts to be presented at ESMO Asia 2023