Sintilimab Injection Second-Line Squamous NSCLC Application Accepted in China

January 14, 2020 — The National Medical Products Administration of China has accepted a supplemental new drug application for sintilimab injection for use in the second-line treatment of patients with squamous non–small cell lung cancer.

The National Medical Products Administration (NMPA) of China has accepted a supplemental new drug application for sintilimab injection (TYVYT) for use in the second-line treatment of patients with squamous non–small cell lung cancer (NSCLC).1

The application is based on findings from the phase 3 ORIENT-3 trial (NCT03150875), in which the PD-1 inhibitor demonstrated superior overall survival (OS) and progression-free survival (PFS) compared with docetaxel in the second-line treatment of patients with advanced and metastatic squamous NSCLC.2 

At a median follow-up of 23.56 months, sintilimab resulted in a median OS of 11.79 months versus 8.25 months with docetaxel (HR, 0.74; 95% CI, 0.56-0.96; P = .02489). Additionally, the median PFS in the investigational arm was 4.30 months versus 2.79 months in the control arm (HR, 0.52; 95% CI, 0.39-0.68; P <.00001).

“In the past few decades, drug development of NSCLC has mainly focused on nonsquamous NSCLC, while drug development of squamous NSCLC has been slower due to its unique epidemiological, histopathological, and molecular characteristics,” professor Yuankai Shi, associate dean of Cancer Hospital, Chinese Academy of Medical Sciences, stated in a press release. “In China, the options for second-line immunotherapy are even more limited. The ORIENT-3 study confirmed that the anti–PD-1 monoclonal antibody sintilimab significantly improved OS for the second-line treatment of [patients with] squamous NSCLC, which is of great clinical value.”

In the open-label, multicenter, phase 3 trial, investigators set out to examine the safety and efficacy of sintilimab injection in the second-line treatment of patients with advanced or metastatic squamous NSCLC.

To be eligible for enrollment, patients had to have histologically or cytologically confirmed squamous cell NSCLC, measurable disease per RECIST v1.1 criteria, be at least 18 year of age but no older than 75 years, have an ECOG performance status of 0-1, a life expectancy of at least 12 weeks, as well as acceptable organ and bone marrow function.3

If they had tumors that harbored EGFR mutations or ALK aberrations; had mixed adenosquamous carcinoma or other pathological tumor type; or had received previous treatment with a PD-1, PD-L1, or CTLA-4 inhibitor, they were excluded.

A total of 290 patients were randomized 1:1 to receive either sintilimab injection at a dose of 200 mg or docetaxel at a dose of 75 mg/m2 every 3 weeks. Treatment was continued until evidence of radiographic disease progression, intolerable toxicity, or treatment discontinuation was required.

The primary end point of the trial is OS, while key secondary end points comprise PFS per investigator assessment in accordance with RECIST v1.1 criteria, objective response rate (ORR), and safety.

Additional results indicated that the ORR with sintilimab was 27.6% (95% CI, 20.5%-35.6%) versus just 5.2% (95% CI, 2.1%-10.4%) with docetaxel.

Regarding safety, 84.7% versus 83.1% of those in the sintilimab and docetaxel arms, respectively, experienced treatment-associated toxicities. The most frequently reported toxicities in the investigative and control arms were hypothyroidism (18.1%) and alopecia (34.6%), respectively. Notably, treatment-related adverse effects that were grade 3 or higher in severity were less common in those who received sintilimab versus those given docetaxel, at 18.1% and 36.2%, respectively. Five patients in the sintilimab arm died versus 1 patient in the docetaxel arm.

Detailed findings will be reported at an upcoming medical meeting or published in an academic journal, according to Innovent Biologics, Inc.

“We are excited about these results, showing [sintilimab injection] significantly improved OS in this patient population. This study underscores the joint commitment from Lilly and Innovent to provide innovative treatment options to patients with lung cancer,” Wang Li, senior vice president of Lilly China and Head of Lilly China Drug Development and Medical Affairs, added in the release. 


  1. Innovent announces NMPA acceptance of a supplemental new drug application for sintilimab as second-line therapy for squamous non-small cell lung cancer. News release. January 12, 2021. Accessed January 14, 2021.
  2. Shi Y, Wu L, Wang M, et al. 30MO ORIENT-3: a randomized, open-label, phase III study of sintilimab versus docetaxel in previously treated advanced/metastatic squamous non-small cell lung cancer (sqNSCLC). Ann Oncol. 2020;31(suppl 7):S1428. doi:10.1016/j.annonc.2020.10.517
  3. A study comparing the efficacy and safety between IBI308 and docetaxel in patients with advanced or metastatic NSCLC. Updated April 15, 2020. Accessed January 14, 2021.