On September 11, 2023 Bristol Myers Squibb (NYSE: BMY) reported six-year results from Part 1 of the Phase 3 CheckMate -227 trial, which continues to demonstrate long-term, durable survival benefits of Opdivo (nivolumab)plus Yervoy (ipilimumab)compared to chemotherapy in the first-line treatment of patients with metastatic non-small cell lung cancer (mNSCLC), regardless of PD-L1 expression levels (Press release, Bristol-Myers Squibb, SEP 11, 2023, View Source;227-Trial-Show-Durable-Long-Term-Survival-with-Opdivo-nivolumab-Plus-Yervoy-ipilimumab-in-the-First-Line-Treatment-of-Patients-with-Metastatic-Non-Small-Cell-Lung-Cancer/default.aspx [SID1234635059]). Follow-up results will be featured in an oral presentation (Abstract #OA14.03) and have been selected for the official press program at the IASLC 2023 World Conference on Lung Cancer (#WCLC23) hosted by the International Association for the Study of Lung Cancer on September 11, 2023, from 2:32 a.m. to 2:42 a.m. EDT / 2:32 p.m. to 2:42 p.m. SGT.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

With a minimum follow-up of over six years (73.5 months), the longest reported for a Phase 3 trial with immunotherapy in mNSCLC:

Follow-up results of the primary endpoint population of patients with tumor PD-L1 expression ≥1% show that the six-year survival rate for Opdivo plus Yervoy was 22%, compared to 13% for chemotherapy (Hazard Ratio [HR] 0.78; 95% Confidence Interval [CI]: 0.67 to 0.91).
In an exploratory analysis of patients with PD-L1 expression <1%, more than three times as many patients treated with Opdivo plus Yervoy were alive at six years compared to those treated with chemotherapy (16% vs. 5%, respectively; HR 0.65; 95% CI: 0.52 to 0.81).
Among those who responded to treatment, greater proportions of patients had tumor burden reduction ≥80% with Opdivo plus Yervoy vs. chemotherapy in both the PD-L1 ≥1% (15% vs. 3%, respectively) and <1% (8% vs. 1%, respectively) subgroups, and six-year overall survival (OS) rates for patients with tumor burden reduction ≥80% with Opdivo plus Yervoy were higher compared to chemotherapy (59% vs. 42% for PD-L1 ≥1% and 77% vs. 0% for PD-L1 <1%, respectively).
The safety profile for the dual immunotherapy combination Opdivo plus Yervoy remained consistent with previously reported data from this trial and was manageable with established protocols, with no new safety signals identified.
"Immunotherapy has transformed the treatment of advanced lung cancer, and thankfully, a diagnosis no longer means the same thing as it used to for many patients. With these six-year results, we are seeing remarkably sustained and durable clinical survival benefits with nivolumab plus ipilimumab year-over-year," said Solange Peters, M.D., Ph.D., professor and chair of medical oncology and the thoracic malignancies program in the Department of Oncology at the University Hospital of Lausanne in Lausanne, Switzerland. "The long-term efficacy seen with the dual immunotherapy regimen in CheckMate -227 reinforce the importance of nivolumab plus ipilimumab to transform outcomes for appropriate patients with metastatic non-small cell lung cancer."

"We are ecstatic to see Opdivo plus Yervoy continue to demonstrate almost double the overall survival rates as chemotherapy after six years of follow-up – the longest-ever for a Phase 3 trial with immunotherapy in metastatic non-small cell lung cancer. Further, the Opdivo plus Yervoy regimen more than tripled survival for patients with PD-L1 expression <1%, a population that is difficult to treat and faces high unmet needs," said Abderrahim Oukessou, M.D., vice president, thoracic cancers global program lead, Bristol Myers Squibb. "Our results presented at WCLC 2023 build on our legacy of transforming survival expectations with immunotherapy combinations. Looking ahead, we are excited to expand our research into targeted and small molecule therapies, as well as additional immunotherapy combinations, in the hope of potentially finding solutions for as many people living with thoracic cancers as possible."

Opdivo plus Yervoy-based combinations have shown significant improvements in OS in six Phase 3 clinical trials in five tumors to date: metastatic NSCLC, metastatic melanoma, advanced renal cell carcinoma, malignant pleural mesothelioma and esophageal squamous cell carcinoma.

About CheckMate -227

CheckMate -227 is a multi-part open-label global randomized Phase 3 trial evaluating Opdivo-based regimens versus platinum-doublet chemotherapy in patients with first-line metastatic non-small cell lung cancer (NSCLC) across non-squamous and squamous tumor histologies.

There are two independent primary endpoints in Part 1 for Opdivo plus Yervoy (versus chemotherapy): overall survival (OS) in patients whose tumors express PD-L1 (assessed in patients enrolled in Part 1a) and progression-free survival (PFS) in patients with tumor mutational burden (TMB) ≥10 mutations/megabase (mut/Mb) across the PD-L1 spectrum (assessed in patients enrolled across Parts 1a and 1b). Patients were treated as follows:

Part 1a: Opdivo (3 mg/kg every 2 weeks) plus Yervoy (1 mg/kg every 6 weeks), Opdivo monotherapy (240 mg every 2 weeks), or chemotherapy (every 3 weeks for up to four cycles) in patients whose tumors express PD-L1 (≥1%)
Part 1b: Opdivo plus Yervoy,Opdivo (360 mg every 3 weeks) plus chemotherapy (every 3 weeks for up to four cycles), or chemotherapy (every 3 weeks for up to four cycles) in patients whose tumors do not express PD-L1 (<1%)
Part 1 met both its independent primary endpoints of PFS with the Opdivo plus Yervoy combination versus chemotherapy in patients whose tumors have high (≥10 mut/Mb) TMB, regardless of PD-L1 expression, and OS demonstrating a superior benefit for Opdivo plus Yervoy versus chemotherapy in first-line metastatic NSCLC patients whose tumors expressed PD-L1 ≥1%.

About Lung Cancer

Lung cancer is the leading cause of cancer deaths globally. The two main types of lung cancer are non-small cell and small cell. Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer, representing up to 84% of diagnoses. Survival rates vary depending on the stage and type of the cancer when diagnosed.