First-line immunotherapy for head and neck cancer! AstraZenecom anti-PD-L1 therapy Imfinzi (Infinfan) Phase 3 clinical failure!

2021 // -- AstraZeneca recently announced the evaluation of anti-PD-L1 therapies The Phase 3 KESTREL trial for first-line treatment of recurrence or metastatic head and neck cancer did not reach the primary endpoint of improved total lifetime (OS).
KESTREL is a randomized, open-label, multi-center, global Phase 3 trial conducted in patients with relapsed or metastatic head and neck squamous cell carcinoma (HNSCC) who had not previously been treated, evaluating the efficacy and safety of the anti-CTLA-4 immunotherapy tremelimumab for first-line treatment and comparing it with standard care program EXTREME (chemotherapy and syxidiosis).
study, high PD-L1 expression levels were defined as ≥50% of tumor cells or ≥25% of tumor-infested immune cells express PD-L1.
trial was conducted at more than 200 clinical centers in 23 countries around the world, including in the United States, Europe, South America and Asia.
end of the drug was the total survival (OS) of the Imfinzi single-drug treatment group in patients with high PD-L1 expression levels.
key secondary endpoint is OS in all patients treated with Imfinzi-tremelimumab.
results showed that imfinzi single-drug therapy did not achieve a significant improvement in total survival (OS) compared to standard care option EXTREME in patients with relapsed or metastasis HNSCC with high levels of tumor expression PD-L1.
, imfinzi-tremelimumab dual immunotherapy did not show OS benefits in all patients compared to the standard care plan EXTREME.
the trial, the safety and toerability of imfinzi monotherapy, Imfinzi and tremelimumab combined therapy were consistent with previous trials.
the experiment will be shared in due course.
, executive vice president of AstraZeneta's oncology division, said: "Metastatic head and neck cancer is a complex and challenging disease with poor prognosmation.
, while we are disappointed with these results, insights from the KESTREL Phase 3 trial will facilitate our understanding and application of immunotherapy throughout the clinical development program.
continue to take advantage of Imfinzi's established strengths in early lung and small cell lung cancer to provide immunotherapy options for all potential beneficiaries.
" head and neck cancer (Photo: Medgadget) By 2020, nearly 750,000 people worldwide will be diagnosed with head and neck cancer.
two-thirds of those patients were diagnosed at an advanced stage, while more than half of those treated eventually relapsed.
patients with incurable or metastasis recurrence had poor prognostics, with a medium survival of less than 1 year.
more than 90% of all head and neck cancers originate from squamous cells in the mouth, nasal cavity and throat, known as head and neck squamous cell carcinoma (HNSCC).
Imfinzi (Infinfan, Dovaliyu monoanti) is an humanized PD-L1 monoclonal antibody that blocks the binding of PD-L1 to PD-1 and CD80, thereby blocking tumor immune escape and releasing suppressed immune responses.
To date, Imfinzi has been approved in several countries (including the United States, Japan, China, and the European Union as a whole) for the healing treatment of non-extinable, stage III non-small cell lung cancer (NSCLC) patients who have not developed the disease after receiving platinum-based chemotherapy synchronous radiotherapy.
In addition, Imfinzi has been approved in the European Union, the United States, Japan and many other countries for the treatment of patients with extensive stage small cell lung cancer (ES-SCLC), as well as in the United States and other countries for the treatment of patients with advanced bladder cancer who have previously received platinum-containing chemotherapy.
Currently, AstraZenecom is conducting a major clinical project to evaluate Imfinzi as a monotherapy and a combination therapy for NSCLC, SCLC, bladder cancer, head and neck cancer, liver cancer, cervical cancer, bile duct cancer and other solid tumors.
tremelimumab is a human monoclonal antibody that targets cytotoxic T lymphocyte antigen 4 (CTLA-4), blocks CTLA-4 activity, promotes T-cell activation, initiates tumor immune response, and promotes cancer cell death.
tremelimumab and Shishi Shiguibo have listed antibody drug Yeervoy (Ipimu monoanti) targeting the same target CTLA-4.
head and neck cancer immunotherapy, in June 2019, The Mercedon anti-PD-1 therapy Keytruda (Corada, generic name: pembrolizumab, Pabliju monoanti) was approved by the FDA for 2 new adaptations, first-line treatment metastatic or non-exsetertic relapse HNSCC patients (1) as a single-drug therapy for patients with tumor expression PD-L1 (combined positive score (CPS) ≥1) and (2) in combination with a commonly used chemotherapy program (platinum-5-fluorouracil) regardless of the patient's tumor PD-L1 expression status.
It is worth noting that Keytruda is the first anti-PD-1 therapy approved for first-line therapy in patients with metastasis or non-excisive relapse HNSCC, and the first anti-PD-1 therapy to significantly improve total lifetime (OS) in such patients.
this approval is based on key Phase 3 clinical studies KEYNOTE-048 (NCT02358031).
This is a randomized, open-label study designed to assess the efficacy and safety of Keytruda as a monotherapy or combination therapy with platinum (cisplatin or carptonine) and 5-fluorouriacine chemotherapy in relation to the current HNSCC first-line treatment standard treatment, EXTREME (Erbitux (cetuximab, situx monoantigen) and platinum (cisplatin or carptonine).
results showed that Keytruda was treated as a single drug therapy (HR-0.74) in the group of patients with head and neck cancer with tumor expression PD-L1 (CPS≥1) compared to exTREME, the first-line standard treatment (HR=0.74. The total lifetime (OS) was significantly extended by p=0.00133) and combined chemotherapy (HR=0.65?95%CI:0.53-0.80), p=0.00002).
Keytruda is a PD-(L)1 tumor immunotherapy that helps detect and fight tumor cells by improving the body's immune system.
Keytruda is an anthogeneic monoclonal antibody that blocks the interaction between PD-1 and its mediators PD-L1 and PD-L2, activating T lymphocytes that may affect tumor cells and healthy cells.
so far, a number of PD-(L)1 oncology immunotherapy therapies have been approved worldwide, with Keytruda leading the field, with more than 20 therapeutic adaptations approved and global sales of $14.38 billion in 2020.
() Original source: Update on KESTREL Phase III trial of Imfinzi with or without tremelimumab in the 1st-line treatment of recurrent or metastatic head and neck cancer<!--/ewebeditor:page->