Zachary Bessette

GI Oncology Now

A novel bispecific PD-1/CTLA-4 antibody demonstrated encouraging tumor response rates with manageable safety profiles in a variety of advanced solid malignancies, according to research published in <a href="https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00411-4/fulltext" target="_blank" rel="noopener">The Lancet Oncology</a>.Previous research has shown that immune checkpoint inhibitors, specifically those targeting PD-1 or CTLA-4, offer substantial clinical benefits in the treatment of a variety of solid malignancies.Jiafu Ji, MD, of the Peking University Cancer Hospital &amp; Institute in China, and colleagues designed a multicenter, open-label, phase 1b/2 trial to assess the safety and antitumor activity of cadonilimab monotherapy, a bispecific PD-1/CTLA-4 antibody, in patients with advanced solid tumors. A total of 240 patients treated across 30 hospitals in China were included in the phase 1b study and 157 patients were enrolled in the phase 2 study.Patients aged at least 18 years with histologically or cytologically confirmed, unresectable advanced solid tumors; unsuccessful completion of at least 1 previous systemic therapy; and an Eastern Cooperative Oncology Group performance status of 0 or 1 were deemed eligible. Those who had previously received anti-PD-1, anti-PD-L1, or anti-CTLA-4 treatment were not eligible.The phase 1b study consisted of a dose-escalation phase and a dose-expansion phase. In the former, patients received intravenous cadonilimab at 6 mg/kg and 10 mg/kg every 2 weeks. In the latter, patients received cadonilimab at 6 mg/kg and a fixed dose of 450&#8200;mg intravenously every 2 weeks.In the phase 2 study, cadonilimab was received at 6 mg/kg intravenously every 2 weeks. Patients enrolled in phase 2 were split into 3 cohorts: cervical cancer (n=111), esophageal squamous cell carcinoma (n=22), and hepatocellular carcinoma (HCC; n=24).The primary end points were safety in the phase 1b study and objective response rate (ORR) in the phase 2 study, based on the Response Evaluation Criteria in Solid Tumors, version 1.1.Dr. Ji and colleagues reported no dose-limiting toxicities during the dose-escalation phase. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 28% (n=67) of patients, with the most frequent grade 3 or worse TRAEs being anemia (3%), increased lipase (2%), decreased bodyweight (1%), decreased appetite (2%), decreased neutrophil count (1%), and infusion-related reaction (1%). Seventeen patients discontinued treatment due to TRAEs, and 54 of the patients reported serious TRAEs, including 5 who died.After a median follow-up of 19.6 months in the phase 2 study for patients with HCC, the ORR was 16.7% (95% CI, 4.7-37.4).Additionally, researchers reported ORRs of 32.3% and 18.2% in the phase 2 cervical and esophageal cohorts, respectively.These &ldquo;encouraging&rdquo; tumor response rates and &ldquo;manageable&rdquo; safety profiles &ldquo;suggest the potential of cadonilimab for the treatment of advanced solid tumors,&rdquo; Dr. Ji and colleagues concluded. They noted that several further studies are underway, including one for HCC (NCT04728321).

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Novel Bispecific Antibody Shows Promise in Advanced Solid Tumors, Including HCC

A novel bispecific PD-1/CTLA-4 antibody demonstrated encouraging tumor response rates with a manageable safety profile.