Sintilimab and Bevacizumab Biosimilar Improve PFS in Advanced Lung Cancer

Investigators have reported significant improvement in progression-free survival (PFS) for patients with nonsquamous non–small cell lung cancer (NSCLC) treated with sintilimab and Byvasda, a bevacizumab biosimilar, in combination with chemotherapy.

Results were presented at the European Society for Medical Oncology Virtual Plenary meeting this month. In the phase 3 ORIENT-31 trial, patients who progressed on epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy were treated with sintilimab (a programmed death inhibitor), a bevacizumab (which inhibits tumor vascularization) biosimilar, pemetrexed, and cisplatin.

Sintilimab, marketed as Tyvyt, and Byvasda are approved in China, and the EGFR-mutated nonquamous NSCLC study was conducted at multiple sites in China. Tyvyt was developed by Innovent Biologics and Eli Lilly, and Byvasda was developed by Innovent Biologics.

Investigators said that in the intent-to-treat patient population, those who received sintilimab plus the bevacizumab biosimilar in combination with chemotherapy demonstrated a statistically significant improvement in PFS compared with patients who received just chemotherapy (HR, 0.46; 95% CI, 0.337-0.639; P < .0001). The median PFS was 6.9 vs 4.3 months, respectively.

They said a third cohort of patients was administered sintilimab and chemotherapy, but findings did not achieve statistical significance in comparison with the sintilimab-plus-bevacizumab- biosimilar-and-chemotherapy cohort.

The investigators said key secondary end points for objective response rate and duration of response showed improvement in the sintilimab-plus-bevacizumab-biosimilar arm vs chemotherapy alone. Safety results were consistent with those previously reported for sintilimab and Byvasda.

Innovent said that it will file an investigational new drug application with China’s National Medical Products Administration based on the findings from ORIENT-31.

Importance of Findings

The results are important because the prognosis for advanced EGFR-mutated NSCLC is very poor, investigators said.

“Despite initial clinical response to EGFR-TKI therapy, virtually all advanced EGFR-mutated NSCLC [cancers] inevitably acquire resistance mechanisms and progress after treatment with an EGFR-TKI,” said Shun Lu, MD, PhD, principal investigator from the Oncology Department of Shanghai Chest Hospital.

The current standard of care for EGFR-mutated advanced nonsquamous NSCLC is platinum-based chemotherapy, although this offers little benefit. “New treatment options are imperative for this unmet medical need,” Lu said.

Investigators said ORIENT-31 was the first prospective, double blind, phase 3 study to demonstrate an improvement in this patient population with sintilimab and bevacizumab in combination with chemotherapy.

"Lung cancer is one of the most prevalent cancers and remains the leading cause of cancer-related mortality both in China and worldwide. EGFR-mutated NSCLC is the most prevalent molecular subtype in Chinese lung cancer patients, accounting for 40% to 50% of nonsquamous NSCLC,” said Hui Zhou, PhD, senior vice president of Innovent.

“While immunotherapy has greatly changed the treatment paradigm for many malignancies, it has not yet conquered driver genes–mutated cancers. Drug resistance is unavoidable for patients with EGFR-mutated advanced NSCLC after first-, second-, and third-generation EGFR-TKI treatments, with limited treatment options, representing a large unmet medical need. The ORIENT-31 data at this year's ESMO indicate the potential of combination therapy to prolong the lives of these patients,” he said.

Innovent was founded in 2011 and has offices in Suzhou, China, and San Francisco, California.