Four-Year Data from Phase 3 CheckMate-227 Trial Demonstrate Durable Survival Benefit of Opdivo (nivolumab) Plus Yervoy (ipilimumab) as First-Line Therapy in PD-L1-Positive Non-Small Cell Lung Cancer

May 21, 2021 /BioonBIOON/ -- Bristol-Myers Squibb (BMS) recently announced 4-year data from the Phase 3 CheckMate-227 trial (NCT02477826) evaluating the anti-PD-1 therapy Opdivo (nivolumab) in combination with the anti-CTLA-4 therapy Yervoy (ipilimumab) as first-line treatment for advanced non-small cell lung cancer (NSCLC). Results from Part 1 of the trial showed that,with a minimum follow-up of 4 years (49.4 months), regardless ofTumorRegardless of PD-L1 expression level or histology, dual immunotherapy with Opdivo plus Yervoy demonstrated durable long-term survival benefits compared with chemotherapy.

It is worth noting that,This is the Phase 3 trial with the longest follow-up evaluating a combination immunotherapy for the treatment of NSCLC.。Data show that, compared with chemotherapy, Opdivo + Yervoy continues to demonstrate a clinically meaningful survival benefit. Over the 4-year follow-up period, inTumorIn the primary patient population with PD-L1 expression ≥1%, the Opdivo + Yervoy treatment group demonstrated improved overall survival and improvements in key secondary endpoints compared with the chemotherapy group. In exploratory analyses of patients with PD-L1 expression <1%, the 4-year survival rate with Opdivo + Yervoy more than doubled compared with the chemotherapy group.

CheckMate-227 Trial Data (Click image to enlarge)

To date,Opdivo + Yervoy Combination Therapy in 6 Phase IIIClinical Trialshowed a significant improvement in overall survival (OS): Metastatic non-small cell lung cancer (CheckMate-227, CheckMate-9LA)Melanoma(CheckMate-067), advanced renal cell carcinoma (CheckMate-214), malignant pleural mesothelioma (CheckMate-743), esophageal squamous cell carcinoma (CheckMate-648).

In May 2020, based on data from Part 1 of the CheckMate-227 trial, the United StatesFDAApproval of Opdivo + Yervoy as first-line treatment for tumors without EGFR or ALK genomic alterations,TumorPatients with metastatic NSCLC expressing PD-L1 (≥1%).

Opdivo + Yervoy (OY combination) is a regulator-approvedThe First and Only Dual Immunotherapy. Opdivo+Yervoy is a unique combination of two immune checkpoint inhibitors, with a potential synergistic mechanism of action,Targeting two distinct checkpoints (PD-1 and CTLA-4), acting in a complementary manner, to help the body destroyTumorcells. To date, the Opdivo + Yervoy combination therapy hasApproved for 7 therapeutic indications across 6 types of cancer（Melanoma, renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, non-small cell lung cancer, malignant pleural mesothelioma).

CheckMate-227 is a global, multi-part, open-label, randomized phase 3 trial conducted in chemotherapy-naïve patients with stage IV or recurrent NSCLC. The study comprises two parts: (1) Part 1: Part 1a compared Opdivo (3 mg/kg) plus Yervoy (1 mg/kg), Opdivo monotherapy, and chemotherapy in patients with PD-L1–expressing tumors; Part 1b compared Opdivo plus Yervoy, Opdivo plus chemotherapy, and chemotherapy treatmentTumorPD-L1-negative patients; (2) Part 2: compares Opdivo in combination with chemotherapy versus chemotherapy, regardless of PD-L1 expression status.

The latest published data indicate that, with a minimum follow-up of over 4 years (49.4 months): (1) inTumorIn patients with NSCLC and PD-L1 expression ≥1%, the 4-year survival rate was 29% in the Opdivo + Yervoy group and 18% in the chemotherapy group (HR = 0.76; 95% CI: 0.65–0.90). (2) In an exploratory analysis of patients with PD-L1 expression <1%, the 4-year survival rate in the Opdivo + Yervoy group was twice that of the chemotherapy group (24% vs 10%; HR = 0.64; 95% CI: 0.51–0.81). (3) The safety profile of the dual immunotherapy was consistent with previously reported data and was manageable, with no new safety signals identified.

University Hospital 12 de Octubre, SpainTumorDr. Luis G. Paz-Ares, Chief of Medical Oncology, stated: "As clinicians, our goal in treating lung cancer is to prolong the lives of patients with lung cancer, which remains the leading cause of cancer death. In the CheckMate-227 trial, the Opdivo plus Yervoy regimen continued to demonstrate durable overall survival and an impressive duration of response after 4 years of follow-up. These data illustrate the significant progress we have made in treating advanced non-small cell lung cancer and underscore the importance of this dual immunotherapy regimen as a first-line option."

CorrectTumorIn an exploratory descriptive analysis of patients with PD-L1 expression (including PD-L1 ≥50%), Opdivo + Yervoy demonstrated an efficacy advantage over Opdivo monotherapy at 4 years, underscoring the importance of Yervoy in improving long-term efficacy. Specific data were as follows: (1) Among patients with PD-L1 expression ≥1%, 29% of patients in the Opdivo + Yervoy group survived, compared with 21% in the Opdivo monotherapy group. (2) Among patients with high PD-L1 expression (≥50%), 37% of patients in the Opdivo + Yervoy group survived, compared with 26% in the Opdivo monotherapy group.

Similarly, inTumorIn an exploratory descriptive analysis of patients with PD-L1 expression <1%, the Opdivo + Yervoy regimen demonstrated an overall survival (OS) benefit compared with the Opdivo + chemotherapy regimen at 4 years, with 4-year overall survival rates of 24% and 13%, respectively.

Patients treated with Opdivo + Yervoy also achieved more durable responses compared with those receiving chemotherapy. These responses persisted after treatment discontinuation; per the trial protocol, treatment was administered for up to 2 years: (1) Among patients with PD-L1 expression ≥1% who responded to Opdivo + Yervoy, 34% remained in response at 4 years, compared with 7% in the chemotherapy group. (2) Among patients with PD-L1 expression <1% who responded to Opdivo + Yervoy, 31% remained in response at 4 years, compared with 0% in the chemotherapy group.

Abderrahim Oukesou, M.D., Vice President and Head of Thoracic Cancer Development at Bristol-Myers Squibb, stated: “With each additional year of follow-up, we continue to see the sustained benefit of the Opdivo + Yervoy combination therapy, not only in lung cancer, but also across several differentTumorType. The 4-year results from the CheckMate-227 trial demonstrate that Opdivo + Yervoy provide improved long-term efficacy, representing the most mature Phase 3 data for this immuno-oncology combination in the first-line treatment of advanced non-small cell lung cancer. We thank the patients and investigators who participated in the trial for enabling this dual immunotherapy to deliver proven benefits to non-small cell lung cancer patients worldwide.” (Bioon.com)

Source: Four-Year Data from Phase 3 CheckMate -227 Trial Show Durable, Long-Term Survival with Opdivo (nivolumab) Plus Yervoy (ipilimumab) in Patients with Non-Small Cell Lung Cancer with PD-L1 Expression ≥1%