Bristol Myers Squibb Announces Phase 3 CheckMate-651 Trial of Opdivo Plus Yervoy Fails to Meet Primary Endpoint in First-Line SCCHN
Jul 17, 2021 00:31
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Head and neck cancer (Image source: lakeshorecancercenter.org)
July 17, 2021 /BioonBIOON/ -- Bristol-Myers Squibb (BMS) recently announced an update to the Phase 3 CheckMate-651 trial. The trial, conducted in patients with platinum-eligible recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), is evaluating the efficacy and safety of the combination of the anti-PD-1 therapy Opdivo (nivolumab) and the anti-CTLA-4 therapy Yervoy (ipilimumab) versus the standard-of-care EXTREME regimen (cetuximab + cisplatin/carboplatin + fluorouracil) for first-line treatment.
The results show,Although Opdivo+Yervoy inTumorA notable positive trend in overall survival (OS) was observed among PD-L1-expressing patients with a Combined Positive Score (CPS) ≥ 20, but the study did not meet its primary endpoint.。In this study, the safety profile of Opdivo and Yervoy was consistent with that previously reported in solid tumor studies.
In the global phase 3 CheckMate-141 trial,Opdivo monotherapy demonstrated a survival benefit in adult patients with recurrent or metastatic SCCHN following platinum-based therapy.. Based on these results, the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA)Opdivo was approved for this indication in 2016.
Furthermore,To date, the Opdivo + Yervoy combination therapy in 5 differentTumorof the 6 Phase IIIClinical Trial`significantly improved overall survival (OS) in: non-small cell lung cancer, metastatic`# Melanoma, advanced renal cell carcinoma, malignant pleural mesothelioma, esophageal squamous cell carcinoma.
Bristol-Myers Squibb stated that it will complete a comprehensive evaluation of the CheckMate-651 trial data and collaborate with investigators to share the results with the scientific community. Dr. Abderrahim Oukessou, Vice President and Head of Thoracic Oncology Development at the company, said: “Extensive data have demonstrated that the Opdivo plus Yervoy combination therapy improves long-term survival in patients with various tumor types, delivering therapeutic benefits to patients worldwide. In the CheckMate-651 trial, Opdivo plus Yervoy inTumor"In patients with PD-L1-expressing squamous cell carcinoma of the head and neck (SCCHN), a positive overall survival trend was observed compared to the EXTREME regimen, although the control arm performed better than expected based on historical data. We are disappointed that these results did not reach statistical significance, but we remain committed to advancing research to support patients with this difficult-to-treat cancer.”
Opdivo + Yervoy (OY combination) is the first and only dual immunotherapy to receive regulatory approval.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) that work in a complementary manner to help the body destroy tumor cells. Yervoy helps activate and promote the proliferation of T cells, while Opdivo helps existing T cells detectTumor. Additionally, certain T cells stimulated by Yervoy also become memory T cells, which may lead to a long-term immune response.
To date,Opdivo + Yervoy combination therapy has been approved for 7 therapeutic indications across 6 cancer types (Melanoma, renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, non-small cell lung cancer, malignant pleural mesothelioma).
Furthermore, the Opdivo + Yervoy combination therapy has already been in 6 Phase 3Clinical Trialshowed a significant improvement in overall survival (OS): non-small cell lung cancer (CheckMate-227, CheckMate-9LA), metastaticMelanoma(CheckMate-067), advanced renal cell carcinoma (CheckMate-214), malignant pleural mesothelioma (CheckMate-743), esophageal squamous cell carcinoma (CheckMate-648).
Head and neck cancer refers to a group of cancers that originate in the head and neck region, typically arising from the squamous cells lining the moist mucosal surfaces in this area, such as those inside the mouth, nose, and throat. Head and neck cancer is the sixth most common cancer globally, with an estimated 930,000 newDiagnosiscases and over 467,000 related deaths. Squamous cell carcinoma of the head and neck (SCCHN) accounts for more than 90% of all head and neck cancers. Risk factors for SCCHN may include behavioral factors (including smoking or alcohol consumption) or viral factors associated with human papillomavirus (HPV).
Notably, in February of this year,AstraZenecaThe Phase 3 KESTREL trial of the anti-PD-L1 therapy Imfinzi (Yingfeifan; generic name: durvalumab) as first-line treatment for recurrent or metastatic head and neck cancer also failed to meet the primary endpoint of improved overall survival (OS).. The trial was conducted in previously untreated patients with recurrent or metastatic SCCHN, and data showed: compared withTumorIn patients with high PD-L1 expression, compared with the standard-of-care EXTREME regimen, Imfinzi monotherapy did not meet the primary endpoint of significantly improving overall survival (OS). Furthermore, in the overall patient population, compared with the standard-of-care EXTREME regimen, Imfinzi plus tremelimumab dual immunotherapy also did not demonstrate an OS benefit.
Regarding first-line immunotherapy for head and neck cancer, in June 2019, Merck's anti-PD-1 therapy Keytruda (Keruida, generic name: pembrolizumab) received U.S.FDAApproved two new indications for the first-line treatment of patients with metastatic or unresectable recurrent SCCHN, specifically: (1) as a monotherapy for patients whose tumors express PD-L1 (Combined Positive Score [CPS] ≥ 1); (2) in combination with a standard chemotherapy regimen (platinum + 5-fluorouracil [5-FU]), regardless of patientsTumorWhat is the PD-L1 expression status?
It is worth noting that,Keytruda is the first anti-PD-1 therapy approved for the first-line treatment of patients with metastatic or unresectable recurrent HNSCC, and the first anti-PD-1 therapy to demonstrate a statistically significant improvement in overall survival (OS) in this patient population.Data from the pivotal Phase 3 KEYNOTE-048 trial (NCT02358031) show that: compared with the standard-of-care EXTREME regimen, Keytruda as monotherapy significantly prolonged OS in the PD-L1-positive (CPS ≥ 1) patient population, and Keytruda combined with chemotherapy (cisplatin or carboplatin plus fluorouracil) significantly prolonged OS in the overall study population. (Bioon.com)