Investigators note a trend towards improved overall survival with cadonilimab plus chemotherapy with or without bevacizumab among those with cervical cancer in the phase 3 AK104-303 trial.
Adding cadonilimab to platinum-based chemotherapy with or without bevacizumab (Avastin) produced a significant improvement in progression-free survival (PFS) among patients with metastatic or recurrent cervical cancer regardless of PD-L1 expression, according to a press release on findings from the phase 3 AK104-303 trial (NCT04982237).1
The PFS improvement with the cadonilimab-based regimen compared with placebo plus chemotherapy with or without bevacizumab reached the trial’s primary end point (P <.0001). Investigators also highlighted a trend towards improved overall survival (OS) with the addition of cadonilimab, although these data are not yet mature at the time of analysis.
The safety profile of the experimental regimen was comparable with previous reports of cadonilimab. There were no new safety signals.
“We are delighted to once again witness the remarkable improvement in [PFS] achieved with cadonilimab in first-line treatment of all-comer patients with advanced cervical cancer,” Yu Xia, PhD, founder, chair, president, and chief executive officer at Akeso, said in the press release.1 “This outcome not only reaffirms the advantages of cadonilimab observed in the phase 2 trials of cervical cancer and other trials, particularly in gastric cancer, but also further validates its exceptional clinical value in cancer treatment.”
The first-in-class bispecific antibody cadonilimab is designed to target both PD-1 and CTLA-4. It is believed that the agent’s lack of binding to Fc receptors demonstrated minimal antibody-dependent cellular toxicity, antibody-dependent cellular phagocytosis, and interleukin-6 (IL-6)/IL-8 release, thereby reducing toxicity when administered as treatment.
In the double-blind AK104-303 trial, patients were randomly assigned to receive cadonilimab or matched placebo plus cisplatin or carboplatin and paclitaxel with or without bevacizumab. All agents were administered intravenously.
The trial’s other primary end point was OS for up to approximately 2 years. Secondary end points included objective response rate (ORR) per RECIST v1.1 criteria, duration of response, time to response, adverse effects, and number of patients who developed anti-drug antibodies.
Patients 18 to 75 years old with histologically or cytologically confirmed cervical cancer not amenable to surgery or concurrent chemoradiation were eligible to enroll on the trial. Additional eligibility criteria included having a life expectancy of at least 3 months, at least 1 measurable lesion based on RECIST v1.1 guidelines, and adequate organ function. All patients were also required to have availability of tumor samples within 2 years prior to treatment randomization.
Patients with clinically significant hydronephrosis that could not be managed with nephrostomy or ureteral stenting or presence of central nervous system metastases were unable to enroll on the trial. Additional exclusion criteria included having other active malignancies within 3 years of enrollment, prior treatment with chemotherapy agents, active or recurrent autoimmune disease, known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation, and serious infections that necessitated hospitalization.
Cadonilimab previously earned marketing approval from China’s National Medical Products Administration for managing relapsed or metastatic cervical cancer that progressed following prior platinum-based chemotherapy in June 2022.2 Supporting data for the approval came from a phase 2 trial in which cadonilimab yielded an ORR of 33.0% and a median OS of 17.51 months among patients with relapsed or metastatic cervical cancer.