First-line treatment with the PD-1/CTLA-4 bispecific antibody cadonilimab in combination with oxaliplatin and capecitabine led to a statistically significant improvement in overall survival vs placebo plus oxaliplatin and capecitabine in patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, meeting the primary end point of the phase 3 AK104-302 trial.
First-line treatment with the PD-1/CTLA-4 bispecific antibody cadonilimab (AK104) in combination with oxaliplatin and capecitabine (Xeloda) led to a statistically significant improvement in overall survival (OS) vs placebo plus oxaliplatin and capecitabine in patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, meeting the primary end point of the phase 3 AK104-302 trial (NCT05008783).1
Findings from an interim analysis showed that the combination of cadonilimab and chemotherapy improved OS irrespective of PD-L1 status, including those with a PD-L1 combined positive score (CPS) of at least 5 and a PD-L1 CPS of less than 5. Safety findings were consistent with prior investigations of cadonilimab, and no new safety signals were reported.
Based on these data, an independent data monitoring committee (IDMC) has recommended the early submission of a supplemental new drug application to China's National Medical Products Administration (NMPA) for cadonilimab in this indication. Detailed findings from the interim analysis will be presented at a future medical conference.
"We extend our sincere gratitude to all the investigators, participants, and patients who actively took part in the clinical trial,” Yu Xia, PhD, founder, chairman, president, and chief executive officer of Akeso, stated in a news release. “Thanks to your dedication and efforts, an estimated 500,000 [patients with] gastric cancer in China may have access to a new bispecific immuno-oncology drug combination therapy offering improved treatment efficiency and survival prospects. We will continue to adhere to the recommendations of IDMC, efficiently promote the study, and engage in proactive communication with China's NMPA regarding the marketing application of cadonilimab for this new indication. We eagerly anticipate the early approval of this innovative therapy for the benefit of patients.”
In June 2022, the NMPA approved cadonilimab for the treatment of patients with relapsed or metastatic cervical cancer who progressed on or after platinum-based chemotherapy.2
The PD-1/CTLA-4 bispecific antibody was further investigated in AK104-302, which was a randomized, double-blind, multicenter, phase 3 study that enrolled patients between 18 and 75 years of age with histopathologically confirmed gastric or GEJ adenocarcinoma. Prior treatment for locally advanced or metastatic gastric or GEJ adenocarcinoma was not permitted; however, prior curative-intent neoadjuvant/adjuvant chemotherapy or chemoradiotherapy was allowed if at least 6 months passed between disease progression and last treatment. At least 1 measurable tumor lesion per RECIST v1.1 criteria was also required.3
Patients were excluded if they had HER2-positive gastric or GEJ adenocarcinoma; had other pathological types, such as squamous cell carcinoma, sarcoma, or undifferentiated carcinoma; received palliative local therapy for non-target lesions, systemic nonspecific immunomodulatory therapy, or Chinese herbal medicine or traditional Chinese medicinal products with antitumor indications within 2 weeks prior to the first study dose; or had known active or untreated brain metastases, meningeal metastases, spinal cord compression, or leptomeningeal disease.
Patients were randomly assigned to receive cadonilimab or placebo on day 1 of each 3-week cycle. All patients received 130 mg/m2 of intravenous oxaliplatin once every 3 weeks plus 1000 mg/m2 of oral capecitabine twice daily. After 6 cycles of chemotherapy, cadonilimab or placebo were continued as maintenance therapy given once every 3 weeks.
Along with the primary end point of OS in the intent-to-treat population, secondary end points included overall response rate, disease control rate, duration of response, time to response, progression-free survival, and safety.