Akeso, a prominent biopharmaceutical company, has ignited a new wave of hope for patients battling advanced gastric and gastroesophageal junction adenocarcinoma with the commencement of its global Phase III clinical trial, COMPASSION-37. The landmark study, which has already enrolled its first patient, will rigorously evaluate the efficacy and safety of cadonilimab, Akeso’s innovative bispecific antibody, as a first-line treatment option.
This pivotal trial marks a significant stride in the ongoing battle against one of the world’s deadliest cancers. Gastric cancer, often diagnosed at advanced stages, presents a formidable challenge, with limited effective treatment options for patients with unresectable or metastatic disease. Cadonilimab, a dual-acting antibody designed to simultaneously target immune checkpoints PD-1 and CTLA-4, holds the potential to revolutionize the therapeutic landscape by enhancing the body’s own immune response against cancer cells.
The COMPASSION-37 study (also known as AK104-311) is a multicenter, randomized, double-blind, placebo-controlled trial that will compare the therapeutic benefit of cadonilimab in combination with standard chemotherapy against chemotherapy administered with or without nivolumab, a widely used PD-1 inhibitor. This comparative design is crucial for definitively assessing whether the unique dual blockade offered by cadonilimab can deliver superior outcomes compared to existing treatment paradigms.
The trial specifically targets patients diagnosed with HER2-negative, untreated, unresectable, or metastatic gastric or gastroesophageal junction adenocarcinoma. This patient population represents a significant unmet need, as current treatments often struggle to achieve durable responses and long-term survival. The study’s global reach underscores Akeso’s commitment to making this potentially life-saving therapy accessible to patients worldwide.
A Chronological Journey Towards a New Therapeutic Frontier
The initiation of COMPASSION-37 is the culmination of years of dedicated research and development by Akeso, building upon a foundation of promising preclinical and earlier-phase clinical data.
Preclinical Development and Early Phase Trials:
Cadonilimab’s journey began with extensive preclinical research demonstrating its potent dual immune checkpoint inhibitory activity. These studies laid the groundwork for its subsequent evaluation in human clinical trials.
COMPASSION-15: Early Promise for Combination Therapy:
A crucial stepping stone in the development of cadonilimab was the COMPASSION-15 study. This earlier trial provided compelling evidence that the combination of cadonilimab and chemotherapy could significantly reduce the risk of mortality in gastric cancer patients. Notably, these benefits were observed across a spectrum of PD-L1 expression levels, suggesting a broad applicability of the treatment. This study was instrumental in informing the design and objectives of the larger, more comprehensive Phase III trial.
Regulatory Milestones and Prior Approvals:
Cadonilimab’s clinical development has also seen significant regulatory progress, demonstrating its therapeutic potential in other cancer types.
- June 2022: Akeso achieved a significant milestone when China’s National Medical Products Administration (NMPA) granted marketing approval for cadonilimab for specific cervical cancer treatments. This marked the first regulatory endorsement of the bispecific antibody, validating its safety and efficacy profile in a clinical setting.
- May 2025: Further bolstering its application in gynecological oncology, cadonilimab, in combination with platinum-based chemotherapy and optionally bevacizumab, received approval for the treatment of persistent, recurrent, or metastatic cervical cancer. These approvals highlight cadonilimab’s versatility and its ability to elicit robust anti-tumor responses.
Advancing into Earlier Stages of Gastric Cancer:
Beyond its application in advanced disease, Akeso is also exploring cadonilimab’s potential in earlier stages of gastric cancer. An international study, led by renowned investigator Dr. Yelena Janjigian, is currently investigating the efficacy of cadonilimab in combination with FLOT chemotherapy (a regimen of fluorouracil, leucovorin, oxaliplatin, and docetaxel) in a perioperative setting for patients with locally advanced, resectable gastric cancer. This research aims to determine if cadonilimab can improve outcomes in the neoadjuvant and adjuvant settings, potentially preventing disease recurrence.
Exploration of Novel Modalities: AK158D1:
Akeso’s commitment to innovation extends to other promising therapeutic modalities. The company recently announced that its investigational bispecific antibody-drug conjugate (ADC), AK158D1, has received clearance from China’s Center for Drug Evaluation (CDE) under NMPA to commence a Phase I trial for patients with advanced malignant solid tumors. This demonstrates Akeso’s forward-thinking approach to developing next-generation cancer therapies.
Supporting Data: The Science Behind Cadonilimab’s Promise
The rationale for cadonilimab’s development is firmly rooted in the understanding of tumor immunology and the critical role of immune checkpoints in regulating anti-tumor immunity.
Dual Immune Checkpoint Blockade:
Cadonilimab is a bispecific antibody engineered to simultaneously inhibit two key immune checkpoints: programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4).
- PD-1: This receptor is primarily expressed on activated T cells and plays a crucial role in preventing T cells from attacking the body’s own tissues. Tumors often exploit the PD-1 pathway by expressing its ligand, PD-L1, on their surface, thereby inducing T cell exhaustion and evading immune surveillance.
- CTLA-4: This receptor is primarily found on T cells and acts as an earlier regulator of T cell activation, particularly in the initial phases of an immune response. By blocking CTLA-4, cadonilimab can enhance T cell proliferation and activation, leading to a more robust anti-tumor immune response.
The simultaneous blockade of both PD-1 and CTLA-4 is hypothesized to offer a synergistic effect, unleashing a more potent and sustained anti-tumor immune response compared to targeting either checkpoint alone. This dual-action approach is particularly relevant in the context of gastric cancer, where immune evasion mechanisms are often complex and multifaceted.
COMPASSION-15: Evidence of Clinical Benefit:
As mentioned, the COMPASSION-15 study provided significant evidence of cadonilimab’s therapeutic potential. This trial demonstrated that the combination of cadonilimab and chemotherapy could lead to a substantial reduction in the risk of mortality. The observation that this benefit was consistent across varying levels of PD-L1 expression is particularly encouraging. PD-L1 expression is often used as a biomarker to predict response to PD-1 inhibitors; however, its utility can be limited, and many patients with low or no PD-L1 expression still benefit from immunotherapy. Cadonilimab’s efficacy across different PD-L1 expression levels suggests a broader patient population could benefit from this novel therapy.
Official Responses: Expert Insights and Optimism
The launch of the COMPASSION-37 trial has garnered significant attention and enthusiasm from leading oncologists and researchers in the field. Their insights highlight the potential impact of cadonilimab on patient care.
Dr. Yelena Janjigian, a leading investigator from Memorial Sloan Kettering Cancer Center, expressed her optimism about the trial’s potential to improve patient outcomes: "Immunotherapy has transformed the treatment of stomach and oesophagus cancers, helping patients live longer and better," she stated. "Through our evaluation of cadonilimab as a potential first-line treatment for advanced disease, we aim to better understand its potential to improve outcomes and support longer-term survival for patients." Dr. Janjigian’s involvement in the trial underscores its scientific rigor and her deep commitment to advancing gastric cancer treatment. Her previous contributions to pivotal trials like CheckMate 649, which demonstrated the value of nivolumab plus chemotherapy, provide a strong foundation for her leadership in COMPASSION-37.
Professor Markus Möhler from Germany and Professors Jiafu Ji and Lin Shen from Peking University, prominent international investigators also involved in the study, bring their extensive expertise in gastrointestinal oncology. Their participation in COMPASSION-37, building upon their prior work in influential trials, is a testament to the global significance of this research.
The collaborative effort of these distinguished clinicians aims to ensure that the COMPASSION-37 trial is conducted with the highest scientific standards, yielding robust and reliable data that can inform future treatment decisions for patients worldwide.
Implications: Reshaping the Treatment Paradigm for Advanced Gastric Cancer
The successful completion and positive outcomes of the COMPASSION-37 trial could have profound implications for the management of unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma.
A New First-Line Standard of Care?
If cadonilimab demonstrates superior efficacy and an acceptable safety profile compared to current first-line treatments, it could establish a new standard of care for this patient population. This would offer a much-needed alternative to chemotherapy alone or chemotherapy in combination with a single immune checkpoint inhibitor, potentially improving progression-free survival, overall survival, and quality of life for countless individuals.
Expanding Treatment Options for HER2-Negative Patients:
The trial’s focus on HER2-negative disease is significant, as this subgroup represents the majority of gastric cancer patients. By developing a targeted therapy for this population, Akeso is addressing a critical unmet need.
Potential for Synergistic Immunotherapy Strategies:
The success of cadonilimab could pave the way for further research into novel immunotherapy combinations. Understanding the interplay between PD-1 and CTLA-4 blockade in gastric cancer may inspire the development of even more sophisticated treatment strategies that harness the power of the immune system to combat cancer.
Global Accessibility and Impact:
Akeso’s commitment to a global Phase III trial signifies a dedication to making this potentially life-saving therapy accessible to patients across diverse geographic regions. If approved, cadonilimab could offer a new beacon of hope to patients in countries where access to innovative treatments has historically been limited.
The COMPASSION-37 trial represents a critical juncture in the fight against advanced gastric cancer. The scientific rationale, coupled with the promising early data and the expertise of the international research team, paints a hopeful picture for the future. As the trial progresses, the global medical community will be keenly watching for results that could potentially redefine the treatment landscape and offer renewed hope to patients facing this devastating disease.
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