Head-to-Head Against Nivolumab: First Patient Enrolled in the International Phase III Trial of First-Line Cadonilimab for Gastric Cancer
The first patient has recently been enrolled in COMPASSION-37 (AK104-311), the international multicenter Phase III trial evaluating Akeso’s (9926.HK) cadonilimab, the world’s first cornerstone drug of immuno-oncology 2.0, combined with chemotherapy versus chemotherapy with or without nivolumab as first-line treatment for previously untreated, HER2-negative, unresectable or metastatic gastric/gastroesophageal junction (G/GEJ) adenocarcinoma.
COMPASSION-37 is led by international experts such as Dr. Yelena Y. Janjigian, Director of the Department of Gastrointestinal Oncology at Memorial Sloan Kettering Cancer Center (MSKCC), Professor Markus Möhler of Johannes Gutenberg University in Germany, Professor Ji Jiafu, Director of the Peking University Cancer Research Center and Director of the Gastrointestinal Center of Peking University Cancer Hospital, and Professor Shen Lin, Director of the Department of Gastrointestinal Oncology at Peking University Cancer Hospital, as global principal investigators.
Dr. Janjigian, Professor Möhler and Professor Shen Lin all participated in the landmark CheckMate-649 study. This study confirms the clinical value of nivolumab combined with chemotherapy in the first-line treatment of advanced gastric cancer, gastroesophageal junction cancer and esophageal adenocarcinoma, and promotes PD-1 monoclonal antibody combined with chemotherapy to become an important first-line treatment option for HER2-negative advanced gastric cancer.
As immunotherapy is widely used in the first-line treatment of gastric cancer, the relationship between PD-L1 expression level and treatment benefit has attracted increasing attention. Studies such as CheckMate-649 have shown that the therapeutic benefits of PD-1 monoclonal antibodies combined with chemotherapy are more prominent in people with high PD-L1 expression. However, for patients with low PD-L1 expression, how to further improve the benefits of immunotherapy is still an important issue in current clinical research.
Dr. Yelena Y. Janjigian said:
"Immunotherapy has revolutionized the treatment of gastric and esophageal tumors, helping patients achieve longer survival and higher quality of life. We conducted the COMPASSION-37 study to evaluate the clinical value of cadonilimab as a potential first-line treatment for advanced gastric cancer, in order to further tap its potential, improve patients' clinical outcomes, and help patients achieve longer survival."
Professor Ji Jiafu said:
“The COMPASSION-15 study has proven that cadonilimab combined with chemotherapy can significantly improve the overall survival of patients with HER2-negative advanced gastric cancer. In patients with PD-L1 CPS <5, we also observed a trend of improved survival benefit of cadonilimab. This suggests that dual immune checkpoint blockade of PD-1 and CTLA-4 may have the potential to expand the number of people benefiting from immunotherapy.
The more important significance of COMPASSION-37 is to further verify the research evidence/results that we have successfully verified in China in a global multi-center, head-to-head phase III study, and directly compare it with the current international standard treatment.
This is not just a matter of Chinese innovative drugs going global. As clinicians, we hope to answer an important clinical question: Can China's innovation results provide more effective and more widely applicable first-line treatment options for patients with advanced gastric cancer with different PD-L1 expression levels, different regions and different populations globally?
We look forward to COMPASSION-37 answering this question with high-quality global clinical evidence, and ultimately allowing innovative treatments with truly clinical value to benefit gastric cancer patients around the world. "
Professor Shen Lin said:
"Advanced gastric cancer has significant biological and clinical heterogeneity. Studies have shown that PD-L1 expression level is closely related to the degree of benefit from PD-1 monoclonal antibody treatment. For patients with low PD-L1 expression, there is still room for existing immunotherapy to further improve the efficacy. Therefore, how to expand the effective population of immunotherapy is an important but not yet fully resolved clinical issue in the field of gastric cancer. We look forward to COMPASSION-37 further clarifying the value of the PD-1/CTLA-4 dual immune checkpoint blockade strategy in different PD-L1 expression subgroups."
COMPASSION-15 to COMPASSION-37:
From China Phase III evidence to global head-to-head verification
COMPASSION-15 is a randomized, double-blind, placebo-controlled phase III study that enrolled 610 patients with HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma. The proportion of patients with low PD-L1 expression and negative PD-L1 included in the study accounted for 49.8% and 23% respectively, which is much higher than similar historical studies. It effectively verifies the strength of cadonilimab beyond single-target drugs, breaking through the efficacy limitation of PD-L1 expression, and possessing the anti-cancer strength of "significant benefits for the entire population (that is, regardless of PD-L1 expression status)". It demonstrates its breakthrough value as a cornerstone drug of tumor immunity 2.0 in continuously upgrading and iterating global treatment standards for major diseases.
The results showed that regardless of the patient's PD-L1 expression status, cadonilimab combined with chemotherapy could significantly reduce the risk of death in the overall population compared with the control group. This suggests that PD-1/CTLA-4 dual immune checkpoint blockade may provide new treatment possibilities for gastric cancer patients with different PD-L1 expression levels, and also provides an important scientific basis for further international head-to-head phase III validation.
Immunotherapy for gastric cancer is moving from “whether to use it” to “who can benefit the most”
Currently, PD-1 monoclonal antibody combined with chemotherapy has become one of the important first-line treatment strategies for HER2-negative advanced gastric cancer. However, multiple clinical studies have shown that the expression level of PD-L1 is closely related to the degree of benefit from immunotherapy. Patients with high expression usually obtain a clearer survival benefit, while patients with low expression have relatively limited absolute benefit.
At the same time, the specific definitions of PD-L1 thresholds by regulatory agencies and clinical guidelines in different countries and regions are not entirely consistent. Therefore, it is not accurate to regard a single CPS threshold as a globally unified immunotherapy access standard.
This also means that the current issues facing gastric cancer immunotherapy have gradually shifted from "whether immunotherapy should be added" to "how to select the most suitable immunotherapy strategy based on the biological characteristics of the tumor, and how to further expand the number of people who can truly benefit from immunotherapy in the long term."
The COMPASSION-37 study was carried out against this background.
Global clinical development of cadonilimab further advances
In addition to COMPASSION-37, international research on cadonilimab in the perioperative treatment of gastric cancer has also been launched.
A Phase II clinical study (NCT07631000) led by Memorial Sloan Kettering Cancer Center and with Dr. Yelena Y. Janjigian as the principal investigator is currently recruiting patients in the United States. This study evaluates cadonilimab combined with FLOT chemotherapy for the perioperative treatment of patients with locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma, and aims to explore the possibility of further expanding PD-1/CTLA-4 dual immune checkpoint blockade to early curable gastric cancer.
From the COMPASSION-15 randomized phase III study in China, to the perioperative phase II study in the United States, to the COMPASSION-37 international multi-center head-to-head phase III study, the clinical development of cadonilimab in gastric cancer is gradually forming a complete research path from late-stage disease to perioperative period, and from Chinese evidence to global validation.
Note: This article is a press release from Akeso to disclose the company’s latest research and development progress. It is not a product promotion advertisement and does not constitute relevant drug use or investment advice.
About Kaitanni® (cadonilimab injection)
Cadonilimab is the world's first PD-1/CTLA-4 bispecific tumor immunotherapy drug independently developed by Akeso. It was approved by the National Medical Products Administration in June 2022 for the treatment of patients with recurrent or metastatic cervical cancer who have previously failed platinum-containing chemotherapy. In September 2024, the cadonilimab combination regimen was approved as a first-line treatment indication for patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma; in May 2025, cadonilimab plus platinum-containing chemotherapy with or without bevacizumab was approved as a first-line treatment for persistent, recurrent or metastatic cervical cancer. Cadonilimab is the world's first new dual-antibody drug for tumor immunotherapy and China's first new bispecific antibody drug. The indications of cadonilimab for the treatment of recurrent or metastatic cervical cancer, first-line treatment of gastric cancer, and first-line treatment of cervical cancer that have failed platinum-containing chemotherapy have been included in the national medical insurance catalog.
Cadonilimab has conducted more than 40 clinical studies for more than 20 indications including gastric cancer, lung cancer, liver cancer, cervical cancer, and pancreatic cancer. 13 phase III/registration clinical studies are in progress, 3 studies have reached the research endpoint, and 2 global phase III/registration clinical studies are being carried out efficiently.
Cadonilimab is a tumor immunotherapy drug with a new mechanism. It can target PD-1 and CTLA-4 at the same time, exert a synergistic anti-tumor effect, and has excellent anti-tumor efficacy. Compared with combination therapy, its toxicity is significantly reduced, and it is safe and tolerable. Multiple clinical studies have shown that cadonilimab has excellent anti-tumor efficacy against both PD-L1 positive and negative patients with a variety of tumor diseases, and has breakthrough clinical value against IO-resistant and other types of cold tumors. Currently, cadonilimab has been highly recommended by 20+ clinical treatment guidelines and consensus, covering multiple indications such as gastric cancer, gynecological cancer, liver cancer, esophageal cancer, nasopharyngeal cancer, and biliary tract cancer.
About Akeso
Akeso (9926.HK) was established in 2012, adhering to the With the original intention of "developing the world's leading innovative drugs in China, allowing patients to be the first to benefit from the world's most advanced treatment options", relying on advanced dual-antibody/multi-antibody technology, the company successfully developed and launched the world's first bispecific antibody drugs cadonilimab (PD-1/CTLA-4 dual-antibody) and ivonescimab (PD-1/VEGF dual antibody) is the only pharmaceutical company in the world with two bispecific cancer immunotherapy drugs. It has opened the global era of immuno-oncology (IO) 2.0 and led a new wave of development of new international dual-antibody drugs. It has grown into a globally innovative and influential company.
Currently, the company has built a unique end-to-end comprehensive new drug research and development platform, using AI intelligent research to empower the entire process of drug development. Based on the advantages of dual-antibody/multi-antibody technology, the company has expanded its research and development territory to ADC/double-antibody ADC, TCE, siRNA, cell therapy, and mRNA. In other cutting-edge technology fields, more than 50 innovative drug candidates have been developed for the treatment of major diseases such as tumors, autoimmunity, respiratory system, central nervous system, inflammation, and metabolic diseases. Nearly 30 new drugs are in the clinical development stage (including 15 bispecific/multispecific antibodies and bispecific ADCs), 8 new drugs have been approved for commercialization, and 5 independently commercialized new drugs with a total of 12 indications have been included in the national medical insurance catalog.
In the field of oncology, Akeso is making every effort to promote the "IO2.0+" strategy and continue to promote the iterative upgrade of treatments for major oncology diseases.
Among them, ivonescimab is the first drug in the world to achieve positive results in a phase III study comparing the "king of drugs" pembrolizumab, and is also the first drug to achieve positive results in OS and PFS in a phase III clinical trial comparing PD-1 monoclonal antibody combined with chemotherapy, a trump card combination therapy in the IO1.0 era. Currently, ivonescimab has achieved positive results in multiple registration/phase III studies. The indications for first-line squamous non-small cell lung cancer, first-line PD-L1-positive non-small cell lung cancer, and non-squamous non-small cell lung cancer with progress in EGFR-TKI treatment have been approved for marketing and included in medical insurance. A total of 16 registration/phase III clinical trials are currently underway, including 6 international multi-center registration/phase III trials.
Cadonilimab is the world's first new bispecific cancer immunotherapy drug, which has filled many gaps in clinical and industrial fields and won the "China Patent Gold Award" from the State Intellectual Property Office. At present, cadonilimab has achieved positive results in multiple registration/phase III studies. The indications for first-line gastric cancer, first-line cervical cancer and recurrent/metastatic cervical cancer have been approved for marketing and included in medical insurance. A total of 13 registration/phase III clinical trials are being carried out, including 2 independent international multi-center registration/phase III clinical trials.
The IO2.0+ADC2.0 global strategy is an important layout for the company to create a therapeutic matrix with cross-generational competitive advantages. At present, ivonescimab/cadonilimab, as the cornerstone drug of IO2.0, has been jointly carried out with multiple self-developed new-generation bispecific ADCs/differentiated single-target ADCs, as well as high-potential ADC products from domestic and foreign companies such as GlaxoSmithKline, Pfizer, Biokin, and Yilian Biotech.
In addition to the field of oncology, the company also continues to promote the upgrading and iteration of treatment options in areas with major unmet clinical needs such as autoimmunity, respiratory and central nervous system diseases. A series of bisAb drugs with global breakthrough clinical value are in efficient clinical development, forming an echelon and complementing new drugs such as ebronucimab, ebdarokimab, and gumokimab that have been commercially sold.
International development is Akeso's core development strategy. Following the first in China to license the rights to independently developed CTLA-4 monoclonal antibody to Merck & Co. in 2015, the company licensed part of the overseas rights and interests of ivonescimab to Summit Therapeutics of the United States with a plan of "US$5 billion + 2-digit percentage sales commission + partner equity", setting a record for the foreign licensing of new drugs in China at that time. In addition, two indications of penpilimab for the treatment of nasopharyngeal carcinoma have been approved by the U.S. Food and Drug Administration (FDA).
Akeso hopes to develop new drugs that are the first in the world and the best treatments of its kind through efficient and breakthrough R&D innovation, provide better disease solutions to patients around the world, and become the world's leading biopharmaceutical company.