Opdivo (nivolumab) Plus Yervoy (ipilimumab) Demonstrates Durable Overall Survival at Three Years in First-Line Unresectable Malignant Pleural Mesothelioma: Phase 3 CheckMate-743 Trial Results

Malignant Pleural Mesothelioma (MPM, Image source: ePainAssist.com)

September 13, 2021 /BioonBIOON/ -- Bristol-Myers Squibb (BMS) recently at the 2021 European MedicalTumorpresented at the virtual European Society for Medical Oncology (ESMO) Congress from the pivotal Phase III CheckMate-743 trial3-Year Data, the results showed:In patients with unresectable malignant pleural mesothelioma (MPM), regardless of histology, first-line treatment with the immunotherapy combination of the anti-PD-1 therapy Opdivo (nivolumab) and the anti-CTLA-4 therapy Yervoy (ipilimumab) demonstrates durable survival benefits compared with platinum-based standard-of-care chemotherapy.。

Minimum follow-up of 3 years (35.5 months): (1)23% of patients in the Opdivo+Yervoy treatment group were still alive at 3 years., whereas the proportion in the chemotherapy group was 15%. (2)Opdivo + Yervoy Dual Immunotherapy Combination Continues to Show Reduced Risk of Death(HR=0.73; 95% CI: 0.61–0.87), demonstrating an improvement over chemotherapy for the trial's primary endpoint, overall survival (OS) (median OS: 18.1 months vs. 14.1 months). (3) The safety profile of Opdivo + Yervoy was consistent with previously reported data in first-line MPM, with no new safety signals identified.

With 3 years of follow-up and approximately 1 year off treatment, compared with chemotherapy, a greater proportion of patients who responded to Opdivo plus Yervoy combination therapy maintained response and had a longer duration of response (DOR), regardless of histology: (1)At the 3-year follow-up, 28% of patients who responded to Opdivo plus Yervoy combination therapy maintained their response, compared with 0% in the chemotherapy group.。（2）The median DOR was 11.6 months for patients treated with Opdivo + Yervoy combination therapy, compared with 6.7 months in the chemotherapy group.。（3）The objective response rate (ORR) in the Opdivo plus Yervoy combination therapy group was comparable to that in the chemotherapy group (39.6% vs 44.0%).。

Thoracic Medical Oncology Service Center, Lausanne University Hospital, SwitzerlandTumorAcademic Chair Dr. Solange Peters, M.D., stated: “For patients with malignant pleural mesothelioma, the prognosis is generally poor, with a 5-year survival rate of approximately 10%. In this aggressive cancer, which has historically had limited treatment options, we now see not only the potential for Opdivo and Yervoy combination therapy to extend patient survival, but also that, compared with chemotherapy, this benefit has persisted for 3 years. These results provide us with further evidence of the durability of outcomes with the Opdivo + Yervoy combination.”

Abderrahim Oukessou, MD, Head of Thoracic Cancer Development and Vice President at Bristol-Myers Squibb, stated: “The results of the CheckMate-743 trial have changed the way physicians treat malignant pleural mesothelioma, a disease that had no new systemic treatment options for nearly 15 years prior to the approval of the Opdivo plus Yervoy regimen. We continue to see more evidence demonstrating that this dual immunotherapy for multiple# Tumorsustained survival benefit, including a durable 4-year overall survival benefit in non-small cell lung cancer (NSCLC). Now, this combination therapy has demonstrated long-term improvement in overall survival in mesothelioma (another thoracic cancer), extending patients' lives.”

The Opdivo + Yervoy combination therapy has been approved by 14 regulatory agencies worldwide for the first-line treatment of unresectable MPM, including the United States, the European Union, Japan, and China. Review of other regulatory submissions is ongoing. To date, in 5Tumorof 6 Phase III trialsClinical TrialIn, Opdivo + Yervoy combination therapy has demonstrated a significant improvement in overall survival (OS): malignant pleural mesothelioma, non-small cell lung cancer, metastaticMelanoma, advanced renal cell carcinoma, esophageal squamous cell carcinoma.

Opdivo+Yervoy is the first new therapy in the past 15 years proven to improve survival in MPM patients.This approval is based on the results of the pivotal Phase 3 CheckMate-743 trial, the first and only positive Phase 3 immunotherapy trial for the first-line treatment of MPM. The results demonstrated that, across all randomized patients, Opdivo plus Yervoy dual immunotherapy (the OY combination) showed a durable survival benefit compared with chemotherapy (pemetrexed plus cisplatin or carboplatin), meeting the primary endpoint of prolonged overall survival (OS).

Opdivo+Yervoy is a unique combination of two immune checkpoint inhibitors with a potentially synergistic mechanism of action, targeting two distinct checkpoints (PD-1 and CTLA-4) to help destroyTumorCell.To date, from a U.S. regulatory perspective, the Opdivo+Yervoy combination therapy has been approved for seven therapeutic indications across six cancer types (melanoma, renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, non-small cell lung cancer, and malignant pleural mesothelioma). In the European Union, Opdivo+Yervoy-based combination regimens have been approved for the treatment of four different types of advanced cancers: mesothelioma, non-small cell lung cancer,Melanoma, renal cell carcinoma.

Malignant pleural mesothelioma (MPM) is a rare, highly aggressiveTumor, which develops in the pleural lining. The most common cause of this disease is associated with the inhalation of asbestos in occupational or residential environments. MPM typically develops approximately 30 to 50 years after asbestos exposure, itsDiagnosisDiagnosis is often delayed, and most patients already present with advanced or metastatic disease at presentation, resulting in a generally poor prognosis: in previously untreated patients with advanced or metastatic MPM, median survival is <1 year, and the 5-year survival rate is approximately 10%.

MPM is a devastating disease with very limited treatment advances over the past 15 years. The standard of care is combination therapy with pemetrexed and cisplatin or carboplatin. The Opdivo plus Yervoy combination regimen will offer a new treatment option for this patient population. Positive results from the CheckMate-743 trial demonstrate the potential of this regimen as a first-line treatment for MPM, while also in multipleTumorAnother example of the efficacy and safety of this dual immunotherapy combination observed in this type.

Both Opdivo and Yervoy are immuno-oncology (I-O) therapies that harness the body's own immune system to combat tumors by targeting distinct regulatory components within the immune system. Specifically, Opdivo targets and blocks the PD-1/PD-L1 pathway, while Yervoy targets and blocks CTLA-4. Currently, Bristol-Myers Squibb is developing the Opdivo + Yervoy immunotherapy combination for multiple types ofTumortreatment of.

Opdivo + Yervoy is the only regulatory-approved dual immunotherapy with a potential synergistic mechanism of action, targeting two distinct immune checkpoints (PD-1 and CTLA-4) and acting in a complementary manner.To date, the Opdivo + Yervoy combination therapy has been approved for 7 indications across 6 types of cancer (Melanoma、renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, non-small cell lung cancer), varying across different countries and regions.(Bioon.com)

Original source:Opdivo (nivolumab) Plus Yervoy (ipilimumab) Demonstrates Durable Overall Survival at Three Years Compared to Chemotherapy in First-Line Unresectable Malignant Pleural Mesothelioma in Phase 3 CheckMate -743 Trial