ORIENT-31 Trial: Sintilimab Combo vs. Chemo Alone in EGFR-Mutant NSCLC

Immunotherapy can be made more effective by using VEGF inhibitors. Although EGFR tyrosine kinase inhibitors have a good response rate at first, nearly all patients acquire resistance to them over time. The purpose of this study was to compare the efficacy and safety of sintilimab plus pemetrexed and cisplatin vs. pemetrexed and cisplatin alone in the treatment of patients with metastatic or locally advanced EGFR-mutated non-small-cell lung cancer (NSCLC) who had disease progression after receiving EGFR tyrosine-kinase inhibitor therapy.

A total of 52 Chinese hospitals participated in this randomized, double-blind, multicenter, phase 3 experiment. Adults with EGFRmut and locally advanced or metastatic NSCLC who progressed on an EGFR tyrosine-kinase inhibitor were eligible for the study. They also needed to have an Eastern Cooperative Oncology Group performance status of 0 or 1 with at least one measurable lesion and a 3-month survival estimate. Block randomization with stratification by sex and presence or absence of brain metastases randomly assigned participants (1:1:1) to receive sintilimab (200 mg) with IBI305 (15 mg/kg) plus pemetrexed (500 mg/m2) and cisplatin (75 mg/m2), sintilimab plus pemetrexed and cisplatin, or pemetrexed and cisplatin (chemotherapy alone).

Each medicine in the research was given IV on cycle day 1, once every 3 weeks. Treatment was continued for 24 months or until disease progression, unacceptable toxic effects, withdrawal of consent, death, or other protocol-specified criteria, whichever came first. Cisplatin was only given in the first four cycles. In the study’s intended-to-treat population, progression-free survival was the major measure of success. Researchers in this study presented the planned interim analysis, comparing sintilimab plus IBI305 plus chemotherapy to chemotherapy alone in terms of progression-free survival. The data on progression-free survival for the sintilimab plus pemetrexed and cisplatin group are not yet ready for reporting.
Among the 936 patients screened between July 11, 2019, and July 31, 2021, 444 were randomly allocated (148 to the sintilimab plus IBI305 plus chemotherapy group, 145 to the sintilimab plus chemotherapy group, and 151 to the chemotherapy alone group).

The interim analysis ended collecting data on July 31, 2021. Progression-free survival was greater in the sintilimab plus IBI305 plus chemotherapy group than in the chemotherapy alone group after a median follow-up of 9 months (IQR 4 months to 13 months]). CI 6-9.3] vs. 4-3.5 months [4-1-5.4]; HR 0.46 [0.34-0.64]; p< 0.0001). Fewer neutrophils (30 [20%] in the sintilimab plus IBI305 plus chemotherapy group, 26 [18%] in the sintilimab plus chemotherapy group, and 27 [18%] in the chemotherapy alone group), fewer white blood cells (17 [11%] vs. 12 [8%] vs. 13 [9%], and anemia (18 [12%] vs. 10 [7%] vs. 15 [10%]) were the most common grade 3 or 4 adverse events associated with treatment.

Six patients in the sintilimab + IBI305 + chemotherapy group and one patient in the chemotherapy alone group experienced potentially treatment-related deaths (one patient each experienced intestinal obstruction, gastrointestinal hemorrhage, and myelosuppression, and three patients died of unknown causes.

Patients with EGFR-mutated NSCLC who had progressed after treatment with an EGFR tyrosine-kinase inhibitor responded favorably to treatment with sintilimab plus IBI305 plus cisplatin and pemetrexed.

Source: https://pubmed.ncbi.nlm.nih.gov/35908558/

Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03802240

Lu, S., Wu, L., Jian, H., Chen, Y., Wang, Q., Fang, J., Wang, Z., Hu, Y., Sun, M., Han, L., Miao, L., Ding, C., Cui, J., Li, B., Pan, Y., Li, X., Ye, F., Liu, A., Wang, K., Cang, S., … Zhang, C. (2022). Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, multicentre, phase 3 trial. The Lancet. Oncology, 23(9), 1167–1179. https://doi.org/10.1016/S1470-2045(22)00382-5

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