EU Approves Opdivo + Yervoy as First-Line Treatment for Unresectable Malignant Pleural Mesothelioma, Marking First Therapeutic Advance in 15 Years

June 04, 2021 /BioonBIOON/ --Bristol-Myers Squibb (BMS) recently announced that the European Commission (EC) has approved the immunotherapy combination of the anti-PD-1 therapy Opdivo (nivolumab) and the anti-CTLA-4 therapy Yervoy (ipilimumab) for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM). In the United States, the Opdivo plus Yervoy regimen received in October 2020FDAApproved for the first-line treatment of adult patients with unresectable MPM.

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

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) to help destroy# Tumorcells. To date, in the United States, the Opdivo + Yervoy combination therapy has been approved for 7 treatment indications across 6 types of cancer (melanoma, renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, non-small cell lung cancer, and malignant pleural mesothelioma). In the European Union, the Opdivo + Yervoy-based combination regimen has been approved for the treatment of 4 different types of advanced cancers: mesothelioma, non-small cell lung cancer,Melanoma, renal cell carcinoma.

Bristol-Myers Squibb Vice President, ThoracicTumorDr. Abderrahim Oukessou, Head of Development, stated: “The European Commission’s approval of the Opdivo plus Yervoy regimen represents a critical step in addressing the significant unmet medical need in patients with malignant pleural mesothelioma. In the CheckMate-743 trial, this dual immunotherapy regimen demonstrated a clinically meaningful improvement in overall survival, surpassing standard-of-care chemotherapy. Among patients treated with Opdivo plus Yervoy, 41% were still alive at two years, compared to only 27% of those who received chemotherapy. We thank the patients and investigators who participated in the CheckMate-743 trial, whose contributions were essential to bringing the first immunotherapy option for mesothelioma to patients across the European Union.”

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

CheckMate-743 is an open-label, multicenter, randomized Phase IIIClinical Trial, a total of 605 previously untreated patients with unresectable MPM were enrolled to evaluate the efficacy and safety of Opdivo + Yervoy dual immunotherapy as first-line treatment, compared with chemotherapy (pemetrexed + cisplatin or carboplatin). In the study, patients were randomized to receive Opdivo + Yervoy (n=303) or chemotherapy (n=302). In the Opdivo + Yervoy arm, Opdivo was administered at 3 mg/kg every 2 weeks and Yervoy at 1 mg/kg every 6 weeks for up to 24 months or until disease progression or unacceptable toxicity. In the chemotherapy arm, patients received cisplatin 75 mg/m² or carboplatin AUC 5 in combination with pemetrexed 500 mg/m² every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicity. The primary endpoint of the study was overall survival (OS) in all randomized patients.

The results showed that the study met its primary endpoint:Compared with the chemotherapy group, the Opdivo + Yervoy group demonstrated a significant improvement in OS (median OS: 18.1 months vs. 14.1 months) and a 26% reduction in the risk of death (HR = 0.74; 95% CI: 0.61–0.89; p = 0.002). At 2 years, the survival rate was 41% in the Opdivo + Yervoy group versus 27% in the chemotherapy group.

Histology is a recognized prognostic factor in mesothelioma, with non-epithelioid patients typically experiencing a poorer prognosis. In the CheckMate-743 study, Opdivo + Yervoy demonstrated improved overall survival in both non-epithelioid and epithelioid MPM, with a greater survival benefit observed in the non-epithelioid subgroup. Specifically, the median OS for epithelioid patients treated with Opdivo + Yervoy was 18.7 months and 18.1 months for non-epithelioid patients, compared with 16.5 months for chemotherapy-treated epithelioid patients and 8.8 months for non-epithelioid patients (epithelioid subgroup: HR=0.86 [95% CI: 0.69, 1.08]; non-epithelioid subgroup: HR=0.46 [95% CI: 0.31, 0.68]).

In this study, the safety profile of Opdivo plus Yervoy dual immunotherapy was consistent with previously reported studies, with no new safety signals observed.

Malignant pleural mesothelioma (MPM) is a rare, highly aggressiveTumor, develops in the lining of the lungs. The most common cause of this disease is associated with the inhalation of asbestos in occupational or environmental settings.MPM occurs approximately 30–50 years after asbestos exposure, and itsDiagnosisOften delayed, most patients already present with advanced or metastatic disease at diagnosis, and the prognosis is generally poor: in previously untreated patients with advanced or metastatic MPM, median survival is <1 year, with a 5-year survival rate of approximately 10%.

MPM is a devastating disease with very limited therapeutic advancements over the past 15 years. The standard of care is pemetrexed in combination with cisplatin or carboplatin. The Opdivo plus Yervoy combination regimen will become a new treatment option for this patient population. The positive results from the CheckMate-743 trial demonstrate the potential of this regimen as a first-line treatment for MPM, and is in multipleTumorAnother example demonstrating the efficacy and safety of this dual immunotherapy combination has been identified 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 of 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 combination immunotherapy for multiple types ofTumortreatment of.

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

Original Source: Bristol-Myers Squibb Receives European Commissionapproval for Opdivo (nivolumab) Plus Yervoy (ipilimumab) as First-Line Treatment for Unresectable Malignant Pleural Mesothelioma