The National Medical Products Administration of China has accepted an application for the PD-1 inhibitor sintilimab injection for use in combination with pemetrexed and platinum-based chemotherapy for the frontline treatment of patients with nonsquamous non–small cell lung cancer.
Li Zhang, MD
The National Medical Products Administration (NMPA) of China has accepted a supplemental New Drug Application (sNDA) for the PD-1 inhibitor sintilimab injection (Tyvyt) for use in combination with pemetrexed (Alimta) and platinum-based chemotherapy for the frontline treatment of patients with nonsquamous non—small cell lung cancer (NSCLC).1
The sNDA is based on findings from the phase 3 ORIENT-11 trial (NCT03607539), in which the sintilimab regimen significantly improved the median progression-free survival (PFS) versus pemetrexed and platinum alone in patients with advanced or recurrent nonsquamous NSCLC without EGFR mutations or ALK rearrangements. At a median follow-up of 8.9 months, the median PFS, per independent review, was 8.9 months versus 5 months, respectively (HR, 0.482; 95% CI, 0.362-0.643; P <.00001).
No new safety signals with sintilimab emerged compared with prior research. The full study details will be presented at a future medical meeting, Innovent Biologics and Eli Lilly and Company, the codevelopers of sintilimab, stated in a press release.
"Nearly half of Chinese patients with nonsquamous NSCLC lack sensitizing EGFR mutation or ALK rearrangement, which makes them not respond to targeted therapy. The ORIENT-11 study has demonstrated a significant delay of disease progression brought by sintilimab in combination with chemotherapy in this patient population,” Li Zhang, MD, the primary investigator of ORIENT-11 and head of the Department of Internal Medicine, Sun Yat-sen University Cancer Center, stated in the press release.
In the double-blind, randomized phase III ORIENT-11 trial, researchers evaluated the efficacy and safety of sintilimab injection or placebo in combination with pemetrexed and platinum-based therapy as a first-line treatment for patients with advanced or recurrent nonsquamous NSCLC without sensitive EGFR mutations or ALK rearrangements. The injection is given at 200 mg along with 4 cycles of pemetrexed/platinum-based therapy, followed by 200 mg of sintilimab injection and pemetrexed maintenance.
To be eligible for enrollment, patients with advanced nonsquamous NSCLC had a life expectancy ≥3 months, ≥1 measurable lesion, an ECOG performance status of 0 or 1, received no prior treatment for advanced disease, and had adequate hematologic, live, or renal function. Those who received prior checkpoint inhibitors, traditional Chinese medicine with an antitumor effect, palliative radiation with 7 days of the first study drug dose, or a physical organ or blood system transplant, among other criteria, were excluded from enrollment.
The primary endpoint was PFS as assessed by the Independent Radiographic Review Committee (IRRC) based on RECIST v1.1 criteria. Secondary endpoints include overall survival (OS), overall response rate, disease control rate, time to response, duration of response, and safety.
Prior phase 1b results of first-line sintilimab in combination with chemotherapy in patients with NSCLC demonstrated efficacy with a tolerable safety profile.2 Patients enrolled had treatment-naïve, unresectable, locally advanced, or metastatic nonsquamous or squamous histology, and were separated into cohorts of differing chemotherapy backbones. Patients were treated with sintilimab at 200 mg intravenously (IV) every 3 weeks in combination with pemetrexed at 500 mg/m2 and cisplatin at 75 mg/m2 IV every 3 weeks for 4 cycles in cohort D (n = 21). In cohort E, sintilimab was given in combination with gemcitabine at 1250 mg/m2 on days 1 and 8 and IV cisplatin at 75 at mg/m2 every 3 weeks for 6 cycles (n = 20).
The median follow-up was 11.4 months in cohort D and 10.3 months in cohort E. Results showed that the median PFS was 11.4 months (95% CI, 3.1—not available [NA]) in cohort D and was 6.5 months (95% CI, 5.3-8.0) in cohort E. The median OS was 18.9 months (95% CI, 5.3-18.9) and was not reached (95% CI, 10.3–NA) in cohorts D and E, respectively. Additionally, the 12-month OS rates were 68% and 64% in cohorts D and E, respectively.
Sintilimab injection was previously granted marketing approval by the NMPA for patients with relapsed/refractory classical Hodgkin lymphoma following second-line chemotherapy.