Combining Novel Monoclonal Antibody With Radiotherapy for NSCLC
Posted: Monday, January 18, 2021
The combination of the fully human IgG4 monoclonal antibody sintilimab with low-dose radiation and stereotactic body radiation therapy (SBRT) appears to be safe and well tolerated in patients with non–small cell lung cancer (NSCLC), according to Jianxin Xue, MD, of West China Hospital, Sichuan University, and colleagues. The results of their dose-escalation and -expansion study were presented during the virtual edition of the 2020 American Society for Radiation Oncology (ASTRO) Annual Meeting (Abstract 148) and published in the International Journal of Radiation Oncology • Biology • Physics.
The study design included a dose-escalation phase (Ia) and dose-expansion phase (Ib) for up to 29 patients with stage IV NSCLC; these patients had PD-L1–positive disease and a minimum of three extracranial tumor lesions. During the dose-escalation phase, patients received SBRT followed by low-dose radiation therapy delivered at three levels: 2 Gy/1f (level 1), 4 Gy/2f (level 2), and 10 Gy/5f (level 3). Within 7 days of completing radiation, patients received 200 mg of sintilimab intravenously once every 3 weeks for a maximum of 24 months. No dose-limiting toxicities were identified, and at least one patient achieved a partial response during dose escalation.
A total of 12 patients were advanced to the dose-expansion phase: six from the level 1 dose escalation and three each from the levels 2 and 3 dose escalations. There were no ≥ grade 3 adverse events.
The overall response rate was 70% (n = 4 at dose level 1 and n = 3 at dose level 2); one patient achieved stable disease at dose level 3. Peripheral blood analysis showed decreased PD-1 expression on CD8-positive T cells and circulating tumor DNA, whereas numbers of T-cell clones and T-cell receptor diversity increased.
“The combination of SBRT plus low-dose radiation therapy plus sintilimab is safe and tolerable,” the researchers noted. “Low-dose radiation therapy at 4 Gy/2f seems to have better tumor responses,” they concluded.
Disclosure: For full disclosures of the study authors, visit redjournal.org.