Editor’s Note: The 2024 ASCO Gastrointestinal Cancers Symposium (ASCO GI 2024) took place in San Francisco from January 18-20, gathering top experts from around the world to share the latest advances in gastrointestinal cancer research. Dr. Zhi Peng from Peking University Cancer Hospital presented two studies (Abstracts 312 and 317) in the poster session, showcasing the contributions of Chinese researchers on the international stage. In an exclusive interview with Oncology Frontier, Professor Peng shared insights on his studies and perspectives on gastric cancer diagnosis and treatment.

Study 1：Atezolizumab and trastuzumab plus chemotherapy in patients with HER2+ locally advanced resectable gastric cancer or adenocarcinoma of the gastroesophageal junction: A multicenter, randomized, open-label phase II study

Study 2：A phase Ib/II study of ASKB589 (anti-Claudin 18.2 [CLDN18.2] monoclonal antibody) combined with CAPOX and PD-1 inhibitor as first-line treatment for locally advanced, relapsed and metastatic gastric/gastro-esophageal junction (G/GEJ) adenocarcinoma

Oncology Frontier: This year at ASCO GI, one of your studies focused on combining atezolizumab, trastuzumab, and chemotherapy for HER2+ locally advanced resectable gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Could you introduce the study background and key results?

Dr. Zhi Peng: We designed this study in 2018-2019, before the KEYNOTE-811 results were published, which explored immunotherapy combined with trastuzumab and chemotherapy as a first-line treatment for HER2-positive advanced gastric cancer or gastroesophageal junction adenocarcinoma. In our clinical practice, we observed that adding immunotherapy to chemotherapy and trastuzumab could increase the objective response rate (ORR) for HER2-positive advanced gastric cancer patients. This prompted us to investigate whether adding atezolizumab could improve outcomes for patients with locally advanced, resectable gastric cancer. We conducted a randomized phase II trial comparing chemotherapy plus trastuzumab with and without atezolizumab in the perioperative treatment of HER2-positive locally advanced gastric cancer, with the primary endpoint being pathological complete response (pCR) rate.

The study found that adding atezolizumab significantly increased the pCR rate in HER2-positive, operable patients (38.1% vs. 14.3%), achieving the expected statistical hypothesis, and the treatment was manageable in terms of safety. Continued follow-up shows a low recurrence rate among these patients, supporting the added efficacy of atezolizumab. This study fills a research gap, offering a promising treatment option for this patient population.

Oncology Frontier: Another study you presented, which explored ASKB589 (a Claudin18.2 inhibitor) combined with CAPOX and a PD-1 inhibitor for first-line treatment of locally advanced, recurrent, and metastatic gastric/GEJ adenocarcinoma, attracted much interest. Could you tell us about this study and its main findings?

Dr. Zhi Peng: Claudin18.2 is an increasingly important target in advanced gastric cancer. The SPOTLIGHT and GLOW phase III trials by Astellas showed positive outcomes with Claudin18.2 monoclonal antibodies combined with chemotherapy as first-line treatments for advanced gastric cancer. However, these findings raise questions for clinicians when choosing a first-line treatment for Claudin18.2-positive advanced gastric cancer: should we use chemotherapy with a Claudin18.2 antibody or the standard first-line treatment with a PD-1 inhibitor?

In early studies with ASKB589, a Claudin18.2 monoclonal antibody developed by Asieris Pharmaceuticals, we observed encouraging efficacy when combined with chemotherapy. Preclinical studies suggest a synergistic effect between ASKB589 and immunotherapy. We aimed to determine if combining ASKB589 with CAPOX and a PD-1 inhibitor could improve outcomes for Claudin18.2-positive advanced gastric cancer patients.

While the follow-up period remains short, the ORR among evaluable patients is impressive at 80.0%, with 100% disease control. The safety profile is manageable, leading us to initiate a phase III, multi-center registration study exploring the efficacy and safety of combining chemotherapy, PD-1 inhibition, and ASKB589 as a first-line treatment for Claudin18.2-positive advanced gastric cancer. We hope this trial will reshape treatment approaches, extending survival and improving quality of life for patients.

Oncology Frontier: How do you see these studies impacting the treatment of gastric/GEJ adenocarcinoma?

Dr. Zhi Peng: For HER2-positive locally advanced gastric cancer, we currently lack standard treatment options and phase III neoadjuvant trial results. The study showed that adding immunotherapy significantly improves short-term outcomes in this population. Several ongoing trials are investigating HER2-positive locally advanced gastric cancer treatment optimization, aiming to increase the cure rate.

For Claudin18.2-positive advanced gastric cancer, the second study highlights the need to improve outcomes in this subgroup. Our phase III randomized trial seeks to provide a robust treatment option that could transform current first-line therapies and prolong survival in advanced cases.

Oncology Frontier: Could you outline your next steps with these studies, and what challenges remain in the field of gastric/GEJ adenocarcinoma?

Dr. Zhi Peng: Given the encouraging results, we plan to conduct studies with larger sample sizes. For HER2-positive locally advanced gastric cancer, we’re initiating a small-scale investigator-led phase II trial to further optimize treatment options and aim for potential cures. Clinical trials can be challenging, but as clinicians, we understand the treatment needs of our patients and feel a duty to improve their survival and quality of life.

For advanced gastric cancer, therapeutic options remain limited. Although we now have immunotherapy and soon Claudin18.2 antibodies, further optimizing treatment strategies is crucial. Our team in the Gastrointestinal Oncology Department at Peking University Cancer Hospital is dedicated to advancing clinical research for this purpose. Numerous trials on new drug combinations and therapies, including ADCs, are underway. Stratifying patients for individualized treatment can improve survival outcomes in gastric cancer.

Dr. Zhi Peng Peking University Cancer Hospital Associate Professor, Chief Physician, PhD Supervisor, Department of Gastrointestinal Oncology

Recognized as a top young talent, Professor Peng has made significant contributions in molecular classification and individualized treatment for gastric cancer, influencing clinical practice and guidelines. He has published over 30 SCI papers as first or corresponding author and received numerous grants and awards for his work in oncology.