Combination sintilimab, IBI305, and chemotherapy could be a new standard of care for patients with EGFR-mutant non-small cell lung cancer (NSCLC) that progressed on an EGFR tyrosine kinase inhibitor (TKI), according to researchers.

The team found that adding sintilimab and IBI305, a bevacizumab biosimilar, to chemotherapy prolonged progression-free survival (PFS) in this patient population. These results, from the phase 3 ORIENT-31 trial, were published in The Lancet Oncology.

“[O]ur results provide strong evidence for this promising treatment strategy and can potentially change the standard of care for a difficult-to-treat patient population,” the researchers wrote.

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The ORIENT-31 trial ( Identifier: NCT03802240) was conducted at 52 hospitals in China. It included 444 patients with locally advanced or metastatic EGFR-mutant NSCLC that had progressed on an EGFR TKI. 

Patients were randomly assigned to 1 of 3 treatment arms: IBI305 plus sintilimab and chemotherapy, sintilimab plus chemotherapy, and chemotherapy alone. The chemotherapy regimen for all arms was pemetrexed plus cisplatin. 

Baseline characteristics were similar across the treatment arms. Most patients were women, had an ECOG performance status of 1, never smoked, and had received a first- or second-generation EGFR TKI. PD-L1 expression levels were unknown for most patients.

For this interim analysis, the median follow-up was 9.8 months. Efficacy data from the sintilimab-chemotherapy arm were not reported.

The combination of IBI305, sintilimab, and chemotherapy significantly prolonged PFS when compared with chemotherapy alone. The median PFS was 6.9 months and 4.3 months, respectively (hazard ratio [HR], 0.46; 95% CI, 0.34-0.64; P <.0001). 

The 6-month PFS rate was 59% in the IBI305 arm and 30% in the chemotherapy-alone arm. The 12-month PFS rate was 28% and 12%, respectively.

The objective response rate was 44% in the IBI305 arm and 25% in the chemotherapy-alone arm. The median duration of response was 8.3 months and 7.0 months, respectively. The disease control rate was 83% and 72%, respectively.

The most common treatment-related grade 3-4 adverse events (in the IBI305 and chemotherapy arms, respectively) were neutropenia (20% vs 18%), leukopenia (11% vs 9%), and anemia (12% vs 10%). 

Treatment discontinuation due to adverse events occurred in 17% of patients in the IBI305 arm and 7% of those in the chemotherapy-alone arm. There were 7 deaths deemed potentially related to treatment — 6 in the IBI305 group and 1 in the chemotherapy-alone group.

“Results from ORIENT-31 support sintilimab and IBI305 plus pemetrexed and cisplatin for the treatment of patients with EGFR-mutated non-squamous NSCLC who have progressed despite receiving EGFR-targeted therapy,” the researchers wrote. 

“This finding is an important advance because such patients had a minimal benefit with PD-1 or PD-L1 monotherapy in preliminary investigations and currently have scarce treatment options and a poor prognosis. However, longer follow-up is required to evaluate contributions of IBI305 and sintilimab to the observed treatment effect.”

Disclosures: This study was supported, in part, by Innovent Biologics. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Lu S, Wu L, Jian H, et al. 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. Lancet Oncol. Published online July 28, 2022. doi:10.1016/S1470-2045(22)00382-5