Opdivo-Yervoy Combo Prolongs Survival in Patients with Advanced NSCLC, Phase 3 Study Shows

A combination of Opdivo (nivolumab) and low-dose Yervoy (ipilimumab) induces significant survival benefits in people with advanced non-small cell lung cancer (NSCLC), compared to chemotherapy alone, data from a Phase 3 trial show.

These findings suggest first-line Opdivo-Yervoy combo as the first immunotherapy to induce better overall survival than chemotherapy in these patients.

The final results of the first part of the ongoing Phase 3 study, called CheckMate-227 (NCT02477826), were recently presented at the European Society for Medical Oncology (ESMO) Congress 2019 in Barcelona, Spain.

Bristol-Myers Squibb‘s Opdivo and Yervoy are two immune checkpoint inhibitors designed to boost the body’s anti-tumor response. They target proteins involved in mechanisms used by cancer cells to evade immune system attack. Opdivo targets the PD-L1 protein on cancer cells, and Yervoy targets the CTLA-4 protein on T-cells — immune cells involved in the fight against cancer.

The open-label, two-part, randomized CheckMate-227 study is evaluating the clinical benefits of Opdivo-based therapy as first-line treatment, compared to standard chemotherapy, in advanced NSCLC patients.

Part 1 of the CheckMate-227 study included two groups of patients with PD-L1-positive tumors (Part 1a; 1189 patients) and PD-L1-negative tumors (Part 1b; 550 patients). They were randomly assigned to receive either Opdivo alone, Opdivo-Yervoy combo, or chemotherapy.

Part 2 was designed to compare a combination of Opdivo plus chemotherapy versus chemotherapy alone, regardless of PD-L1 status.

Opdivo was administered at 3 mg/kg every two weeks, and a low dose of Yervoy (1 mg/kg) was given every six weeks.

The two main goals of Part 1 focused on whether the Opdivo-Yervoy combo showed greater clinical benefit than chemotherapy in terms of progression-free survival (PFS) — the time a patient lives without signs of disease progression — in patients with a high tumor mutational burden (TMB), regardless of PD-L1 expression, and overall survival in patients with PD-L1-positive tumors.

Secondary goals involved the assessment of PFS, objective response rate (the proportion of patients showing a reduction in tumor burden), and duration of response between combination therapy and chemotherapy in patients with PD-L1-positive tumors.

As previously reported, the study’s primary goal was met in patients with high TMB, with the Opdivo-Yervoy combo significantly extending the time to disease worsening or death from any cause in these patients.

The results presented at the ESMO conference show that the second primary goal was also met, with the combination extending the lives of patients with PD-L1-positive tumors from 14.9 to 17.1 months. At two years of treatment, 40% of patients in the combination were alive, compared with 32.8% of those on chemotherapy alone.

“These positive results validate the immunologic rationale for the dual [block] of PD-1 and CTLA-4 in the treatment of lung cancer,” Martin Reck, MD, PhD, the study’s investigator, said in a news release.

First-line Opdivo-Yervoy combination therapy in these patients has “the potential to deliver deep and durable responses, with a clear survival benefit … without the need for chemotherapy,” he said.

Opdivo-Yervoy combo also led to greater response rates (35.9%) than chemotherapy (30.0%) in these patients and longer responses to treatment (23.2 months in the combo group versus 6.2 months in the chemo group). The proportion of patients achieving a complete response (or complete tumor elimination) was also better with the combination (5.8% versus 1.8% for the chemo group).

In an exploratory analysis, the researchers also found that, compared to chemotherapy, the combination therapy induced an overall survival benefit and better treatment responses in PD-L1-negative tumors.

Independent of tumor positivity for PD-L1, the patients treated with Opdivo-Yervoy combo had a nearly four-times longer duration of response, compared with those given chemotherapy.

Opdivo-Yervoy combo’s safety profile was consistent with that reported in previous trials involving NSCLC patients, and no new adverse events were observed.

“Opdivo and Yervoy [is] the first and only dual [immunotherapy] to demonstrate superior overall survival over chemotherapy in first-line non-small cell lung cancer,” said Fouad Namouni, MD, Bristol-Myers Squibb’s head of oncology.

“We look forward to sharing these data with regulatory authorities and through continued research, expanding our understanding of the value of this unique combination for patients with cancer,” Namouni added.

Bristol-Myers Squibb has announced that the main goal of Part 2 — to assess whether combining Opdivo and chemotherapy led to a significantly greater overall survival compared to chemotherapy alone — was not achieved.