ORIENT-11 Trial Shows Sintilimab Plus Chemotherapy Improves Progression-Free Survival in Advanced NSCLC

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The first-line setting for patients with locally advanced or metastatic non-squamous non–small cell lung cancer (NSCLC) now has become more complicated, according to data presented during the 2020 International Association for the Study of Lung Cancer’s World Conference on Lung Cancer Virtual Presidential Symposium.1

The addition of sintilimab, an anti–PD-1 antibody, to pemetrexed and platinum-based therapy significantly improved progression-free survival versus chemotherapy alone in patients with locally advanced or metastatic nonsquamous NSCLC. At a median follow-up of 8.9 months, results of the phase III ORIENT-11 trial showed a median progression-free survival of 8.9 months (95% confidence interval [CI] = 7.1–11.3 months) in the sintilimab arm compared with 5.0 months (95% CI = 4.8–6.2 months) in the chemotherapy-alone arm.

“The benefit [of sintilimab] was seen across key clinical subgroups,” said lead study author Li Zhang, MD, Professor of Medical Oncology; Director of Medical Oncology Department and Phase I Unit of Sun Yat-Sen University Cancer Centre; and Deputy Director of Lung Cancer Research Centre of Sun Yat-Sen University, China. “The overall response rate was also significantly improved, with a durable response.”

Li Zhang, MD

Li Zhang, MD

As Dr. Zhang explained, sintilimab is a fully human IgG4 monoclonal antibody that blocks the binding of PD-1 to PD-L1 or PD-L2, along with high affinity to human PD-1 and high PD-1 receptor occupancy. Phase Ib data of sintilimab plus pemetrexed/platinum previously demonstrated tolerable safety profile and activity in patients with treatment-naive, nonsquamous NSCLC.2

Study Design

For this double-blind, randomized, phase III study, Dr. Zhang and colleagues evaluated the efficacy and safety of sintilimab in combination with pemetrexed and platinum as first-line therapy in patients with nonsquamous NSCLC in China (n = 397). To be eligible for enrollment, patients were required to have stage IIIB/C or IV disease that was ineligible for surgery or local therapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, and a provision of tumor sample for PD-L1 assessment. Investigators stratified patients by gender, type of platinum therapy (cisplatin vs carboplatin), and PD-L1 expression level.

Patients were randomly assigned to receive either sintilimab combined with pemetrexed plus cisplatin or carboplatin (n = 266) or placebo combined with the same chemotherapy regimen (n = 131) every 3 weeks for four cycles. Patients then received either maintenance therapy with sintilimab plus pemetrexed or placebo plus pemetrexed. Treatment was continued until disease progression, with crossover to sintilimab monotherapy allowed in the placebo arm.

The primary endpoint of the study was progression-free survival evaluated by independent radiologic review committee. Secondary endpoints included overall survival, objective response rate, duration of response, time to response, and safety. The protocol specified one interim analysis to be performed when 70% of progression-free survival events were achieved. The data cutoff date was November 15, 2019.

Survival Benefit Across All Key Subgroups

As Dr. Zhang reported, 56.8% of patients (n = 151) randomly assigned to the sintilimab combination remain on treatment, whereas 43.2% (n = 115) discontinued therapy. The majority of these patients stopped treatment due to disease progression, he added.

Of those patients randomly assigned to the placebo combination, 35.1% (n = 46) remain on that treatment, whereas 64.9% (n = 85) have stopped that treatment. In addition, 31.3% of patients (n = 35) on the placebo arm crossed over to receive sintilimab.

At a median follow-up of 8.9 months, the median progression-free survival was 8.9 months with sintilimab vs 5.0 months with chemotherapy alone, translating to an estimated 52% reduction in the risk of disease progression or death (hazard ratio = 0.48). The 6-month overall survival rates were 89.6% and 80.4%, respectively.

Moreover, progression-free survival benefit with sintilimab was reported across key subgroups, including age, performance status, platinum-based therapy, smoking status, and presence of brain metastases, said Dr. Zhang.

Of note, progression-free survival benefit correlated with the level of PD-L1 expression. In patients with less than 1% expression, the median progression-free survival with sintilimab was 7.3 months vs 5.1 months with chemotherapy alone. For patients with PD-L1 expression between 1% and 49%, the median progression-free survival was 7.1 months vs 4.8 months, respectively. For patients with PD-L1 expression 50% or higher, however, the median progression-free survival has not been reached with sintilimab vs 5.0 months with chemotherapy alone.


  • Sintilimab injection plus chemotherapy led to a statistically significant improvement in progression-free survival vs chemotherapy alone in patients with locally advanced or metastatic nonsquamous NSCLC (8.9 vs 5.0 months; hazard ratio = 0.48).
  • The overall response rate was also improved with sintilimab (51.9% vs 29.8%), with durable responses.

The overall response rate with the sintilimab regimen was 51.9%, including a 1.1% complete response rate and a 50.8% partial response rate. The overall response rate in the placebo arm was 29.8%, comprised entirely of partial responses.

Moreover, the median duration of response has not been reached in the sintilimab arm vs 5.5 months in the placebo arm. The time to response was also shorter with the sintilimab combination compared with the placebo combination (1.5 vs 2.6 months, respectively).

The rates of adverse events were similar between arms, said Dr. Zhang, who noted the safety profile was manageable and no new safety signals were observed.

Based on these study results, the National Medical Products Administration of China accepted a supplemental new drug application in April 2020 for sintilimab injection for use in combination with pemetrexed and platinum-based chemotherapy for the front-line treatment of patients with nonsquamous NSCLC.

DISCLOSURE: This study is sponsored by Innovent Biologics and Eli Lilly & Co. Dr. Zhang has received research grants from Eli Lilly & Co and Pfizer.


1. Zhang L, Yang Y, Wang Z, et al: ORIENT-11: Sintilimab + pemetrexed + platinum as first-line therapy for locally advanced or metastatic non-squamous NSCLC. 2020 World Conference on Lung Cancer. Presidential Symposium. Abstract 1.

2. Xu N, Ying K, Wang Z, et al: Phase Ib study of sintilimab in combination with chemotherapy for 1L advanced or metastatic non-small cell lung cancer (NSCLC). 2019 ASCO Annual Meeting. Abstract e20546.

3. Innovent and Eli Lilly announce NMPA acceptance of a supplemental new drug application for sintilimab in combination with Alimta (pemetrexed) and platinum as first-line therapy in non-squamous NSCLC. April 23, 2020. Available at Accessed August 21, 2020.


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