The first-line combination of sintilimab injection plus pemetrexed and platinum-based therapy showed a statistically significant improvement in progression-free survival compared with chemotherapy and placebo in patients with advanced or recurrent nonsquamous non–small cell lung cancer who did not harbor EGFR or ALK abnormalities, according to an interim analysis of the phase III ORIENT-11 trial.
Li Zhang, MD
Li Zhang, MD
The first-line combination of sintilimab injection (Tyvyt) plus pemetrexed (Alimta) and platinum-based therapy showed a statistically significant improvement in progression-free survival (PFS) compared with chemotherapy and placebo in patients with advanced or recurrent nonsquamous non—small cell lung cancer (NSCLC) who did not harbor EGFR or ALK abnormalities, according to an interim analysis of the phase III ORIENT-11 trial (NCT03607539).1
In the Chinese study, results showed that the combination met the predefined efficacy criteria of the interim analysis, which was conducted by the Independent Data Monitoring Committee (IDMC). The safety profile of sintilimab injection was found to be consistent with prior studies, and no new safety signals were identified.
Further findings will be presented at an upcoming medical meeting. Based on a recommendation from the IDMC, Eli Lilly and Company and Innovent, the companies that are jointly developing sintilimab and pemetrexed, stated that they will initiate regulatory discussions with the National Medical Products Administration (NMPA) in China in the near future.
"In 2019, the National Cancer Center published Chinese data on lung cancer from 2015, showing an incidence of 20% and a mortality rate of about 27%, ranking it first among all cancer types,” Li Zhang, MD, head, Department of Internal Medicine, Sun Yat-sen University Cancer Center, stated in a press release. “Patients who have nonsquamous NSCLC without sensitive EGFR mutations or ALK rearrangements need more treatment options. Treatment with an anti—PD-1 monoclonal antibody in combination with chemotherapy may bring a greater survival benefit to this patient population. We are glad to see that these findings from this trial of sintilimab met the predefined primary endpoint in the interim analysis."
Sintilimab injection is a PD-1 inhibitor that has previously been granted marketing approval by the NMPA for patients with relapsed/refractory classical Hodgkin lymphoma following second-line chemotherapy. The agent is also listed in the 2019 Guidelines of Chinese Society of Clinical Oncology for Lymphoid Malignancies, and was included in China’s National Reimbursement Drug List in November 2019.
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 is 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.
"We are excited about these results, which show Tyvyt plus Alimta and platinum significantly delayed disease progression in this patient population. This study is another example of the joint commitment from Lilly and Innovent to provide new treatment options to patients with lung cancer," Wang Li, MD, PhD, senior vice-president of Lilly China and head of Lilly China Drug Development and Medical Affairs, stated in the press release. "We would like to thank the patients, investigators and clinical trial sites that are participating in the study, and our colleagues from Innovent. We look forward to bringing this new treatment option to lung cancer patients in China."
Prior phase Ib 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.