Frontline treatment with AK112, a first-in-class humanized IgG1 bispecific antibody, plus chemotherapy demonstrated promising overall responses across 3 cohorts in a phase 2 trial.
First-line treatment with ivonescimab (AK112) in combination with chemotherapy appeared safe and effective in patients with advanced non-small cell lung cancer (NSCLC), according to results from an open-label, multicenter, phase 2 trial (NCT04736823).
Antitumor activity was seen in patients without driver mutations, as well as those with EGFR-functional mutations who failed previous EGFR tyrosine kinase inhibitor (TKI) therapy and those who failed prior systemic platinum-based chemotherapy and PD-1/PD-L1 inhibitor treatments, “suggesting a valuable potential new treatment option for this patient population,” the investigators wrote.
“To the best of our knowledge, this was the first phase 2 trial evaluating the efficacy and safety of a bispecific antibody targeting PD-1 and VEGF (AK112) in combination with chemotherapy in metastatic NSCLC, including both non-squamous and squamous NSCLC,” they added.
In the trial, which was conducted in 11 hospitals in China from February 2021 to August 2022, AK112–a global first-in-class humanized IgG1 bispecific antibody that targets PD-1 and VEGF, inhibits PD-1-mediated immunosuppression, and blocks tumor angiogenesis in the tumor microenvironment–was administered to 83 patients across 3 cohorts:
Doses of 10 mg/kg or 20 mg/kg, administered intravenously on day 1 of each 3-week treatment cycle, were examined in each cohort.
The confirmed objective response rates (ORRs) in cohorts 1, 2, and 3 were 53.5% (95% CI, 36.9%-67.1%), 68.4% (95% CI, 43.4%-87.4%), and 40.0% (95% CI, 19.1%-63.9%), respectively.
Further, median PFS was not reached in cohort 1, 8.5 months (95% CI, 5.5-not evaluable [NE]) in cohort 2, and 7.5 months (95% CI, 2.3-NE) in cohort 3, with 12-month PFS rates of 59.1%, 35.5%, and 44.5%, respectively.
In cohort 1, the disease control rate (DCR) was 93.0% (95% CI, 80.9%-98.5%). In patients with non-squamous and squamous NSCLC, the confirmed ORRs were 48.0% (95% CI, 27.8%-68.7%) and 61.1% (95% CI, 35.7%-82.7%), respectively.
In addition, the DCRs in cohorts 2 and 3 were 94.7% (95% CI, 74.0%-99.9%) and 70% (95% CI, 45.7%-88.1%), respectively.
The most common grade ≥3 treatment-related adverse events across all 3 cohorts were decreased white blood cell count (8.4%), neutropenia 6.0%), thrombocytopenia (2.4%), anemia (4.8%), and myelosuppression (2.4%).
Patients were eligible for the trial if they were aged 18 to 75 years, had locally advanced or metastatic NSCLC, had an ECOG performance status of 0 or 1, had at least 1 measurable lesion, and had an estimated life expectancy of at least 3 months.
Investigator-assessed ORR and safety served as the primary end points of the trial.
“Our results supported the further evaluation of AK112 in combination with chemotherapy in treating NSCLC,” the investigators concluded. “AK112 may be a valuable potential new treatment option for this patient population. Based on the results of the present study, a phase 3 randomized control trial of AK112 plus chemotherapy in NSCLC patients with EGFR mutation who progressed with previous EGFR-TKI is now ongoing (NCT05184712).”
Zhao Y, Chen G, Chen J, et al. AK112, a novel PD-1/VEGF bispecific antibody, in combination with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC): an open-label, multicenter, phase II trial. eClinicalMedicine. 2023;62:102106. doi:10.1016/j.eclinm.2023. 102106.