Sintilimab With Bevacizumab Biosimilar and Chemotherapy Extends PFS in EGFR-NSCLC

The combination of sintilimab (Tyvyt) plus a bevacizumab biosimilar injection (IBI305, Byvasda) and chemotherapy significantly improves progression-free survival (PFS) in patients with EGFR-mutated non-small cell lung cancer (NSCLC) who progressed after EGFR tyrosine kinase inhibitor (TKI) therapy, according to data presented at the European Society of Medical Oncology Virtual Plenary 2021.¹

The standard first-line treatment for patients with advanced EGFR-mutated NSCLC is an EGFR TKI. For patients who progress on or after this treatment, platinum-based chemotherapy is currently the standard of care. However, it yields limited benefit in most patients. An effective second-line therapy remains a large, unmet clinical need.

"Despite initial clinical response to EGFR-TKI, virtually all advanced EGFR-mutated NSCLC inevitably acquire resistance mechanisms and progress after treatment with an EGFR-TKI. For those patients with EGFR-mutated advanced nsqNSCLC who have progressed following EGFR-TKI treatment, platinum-based chemotherapy is the current standard of care, but with limited benefit. New treatment options are imperative for this unmet medical need. Globally, ORIENT-31 is the first prospective, double-blind Phase 3 study to demonstrate significant PFS benefit of combination therapy of PD-1 and VEGF inhibitors with chemotherapy compared to standard care of therapy in this patient population. The study has shown the clinical value of adding sintilimab plus Byvasda® [bevacizumab biosimilar injection] to platinum-based chemotherapy,” said principle investigator Shun Lu, MD, PhD, of the Oncology Department of Shanghai Chest Hospital, in a press release.

The data comes from an analysis of the phase 3 ORIENT-31 trial (NCT03802240), a Chinese study with an estimated enrollment of 600 participants. The randomized, parallel assignment quadruple masked study has a primary end point of progression-free survival. Secondary end points include overall survival and overall response rate.²

During the study (NCT03802240), patients were randomized 1:1:1 into 3 arms. In arm 1, patients received a combination of sintilimab, IBI305 and pemetrexed/cisplatin chemotherapy. In arm 2, patients received the same regimen with the exception of a placebo in place of IBI305. In arm 3, patients received the chemotherapy combination and placebos in place of sintilimab and IB1305.

The first interim analysis found that patients in arm 1 had significantly improved PFS compared with patients in arm 3 (HR, 0.464; 95% CI, 0.337-0.639; P <.0001). In arm 1, the median PFS was 6.9 months (range, 6-9.3) and 4.3 months (range, 4.1-5.4) in arm 3. PFS data comparing arm 2 to arm 3 is immature, however, a numerical benefit was observed as well.

In terms of safety, no new or unexpected safety signals were observed. Overall, the safety profile was consistent with other studies of sintilimab and IBI305.

"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 nsqNSCLC. 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-TKIs treatments, with limited treatment options, representing a large unmet medical need. The ORIENT-31 data at this year's ESMO indicates the potential of combination therapy to prolong lives of these patients. We are grateful for all the contributions made by the investigators and patients in the ORIENT-31 study – together we accomplished this meaningful milestone,” said Hui Zhou, MD, senior vice president of Innovent,, in a press release.

In order to participate, patients must be between 18 and 75 years of age, have confirmed IIIB/IIIC NSLCLC that is unrespectable and not fit for radical concurrent chemotherapy, or metastatic/recurrent non-squamous NSCLC, have a confirmed EGFR mutation, EGFR- TKI resistance, at least 1 measurable lesion, and an ECOG performance status of 0 or 1. Patients with >10% squamous cells, have received anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs, have received an EGFR-TKI within 2 weeks, a diagnosed immunodeficiency disorder, a history of pneumonitis, active central nervous system metastasis, or hemoptysis within 3 months are not eligible to participate.

_REFERENCES:

_{Innovent releases the ORIENT-31 phase 3 study first interim analysis results of sintilimab plus Byvasda (bevacizumab biosimilar injection) and chemotherapy in patients with EGFR-mutated nonsquamous non-small cell lung cancer who progressed after EGFR-TKI Therapy at ESMO Virtual Plenary 2021. News release. Innovent. November 21, 2021. Accessed November 22, 2021. https://bit.ly/3cAvdFR}

_{Sintilimab ± IBI305 Plus chemotherapy (pemetrexed + cisplatin) for EGFRm + locally advanced or metastasis non-squamous NSCLC patients after EGFR-TKI treatment failure. ClinicalTrials.gov Accessed November 22, 2021. https://bit.ly/32tuswB}