Merck/Eisai "Immunity + Targeting" Combination for lung cancer failed

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Merck/Eisai “Immunity + Targeting” Combination for lung cancer failed

Merck/Eisai “Immunity + Targeting” Combination for lung cancer failed.

First-line treatment of lung cancer failed! Merck/Eisai “Immunity + Targeting” Combination Hits Hard.

Merck Keytruda is the king of tumor immunotherapy, with sales in the first three quarters of this year reaching 12.578 billion US dollars.

Currently, the company is exploring the therapeutic potential of Keytruda monotherapy and various combination therapies in multiple cancers through a huge clinical development project.

In March 2018, Merck and Eisai signed a cooperation agreement totaling US$5.8 billion to develop oral multi-receptor tyrosine kinase inhibitor Lenvima (lenvatinib) monotherapy and combination therapy with Keytruda.

Through the LEAP (LEnvatinib And Pembrolizumab) project, the two parties are evaluating the Keytruda+Lenvima combination in more than 10 different types of tumors.

The data from this project shows that the combination has shown strong efficacy in multiple types of tumors.

In terms of supervision, the combination has also obtained 2 indications.

However, in terms of lung cancer, the combination has recently suffered a major setback. According to the data released at the ESMO Virtual Conference on Immuno-oncology, in the first-line treatment of non-small cell lung cancer (NSCLC) patients whose tumors express PD-L1 (CPS ≥ 1%), compared with Keytruda monotherapy, “immunity + targeting” “The combination Keytruda+Lenvima failed to prolong the life of the patient.

According to the researchers, from the interim observation results of the Phase 3 LEAP-007 trial, Keytruda monotherapy is still the standard care plan for this patient group.

But this failure did raise industry analysts’ concerns about the prospects of other joint trials of Keytruda and Lenvima in the treatment of NSCLC.

The results of the LEAP-007 trial showed that the median overall survival (OS) of the patient group receiving Keytruda+Lenvima first-line treatment was 14.1 months, which was even shorter than the median OS (16.4 months) of the Keytruda monotherapy group.

In terms of safety, the incidence of side effects related to grade 3-5 treatment in the combination therapy group was also significantly higher than that in the Keytruda monotherapy group (57.9% vs 24.4%).

In addition, no survival benefit was observed in all patient subgroups.

Hossein Borghaei, head of thoracic oncology at Fox Chase Cancer Center, said in a speech at ESMO IO that the most notable thing is that this combination did not show any advantages in patients with a high PD-L1 expression of more than 50%.

What the doctors hope to see is that there is at least a low level of improvement in this population.

Compared with Keytruda monotherapy, the combination of Keytruda+Lenvima did reduce the overall risk of tumor progression or death by 22%, but this did not translate into prolonged survival.

Roy Baynes, chief medical officer of Merck Research Laboratories, said in an interview that compared with Keytruda+ chemotherapy, Keytruda monotherapy is usually used for patients with comorbidities.

He pointed out that the additional side effects of Lenvima in these frail people may have affected the positive results of the LEAP-007 test.

Although the first-line treatment of NSCLC has failed, the combination therapy of Keytruda and Lenvima has been approved by the US FDA for several indications, including the approval of the first-line treatment of renal cell carcinoma (RCC) in August.

However, the failure of the LEAP-007 trial seems unknown for other NSCLC trials of this combination.

The LEAP-006 trial, which has been fully enrolled, is testing whether the addition of Lenvima to the Keytruda+ chemotherapy regimen can bring additional benefits to the first-line treatment of non-squamous NSCLC patients.

Through the landmark KEYNOTE-189 trial, Keytruda+ chemotherapy has set a high standard for this indication.

The interim analysis of the trial showed that this regimen reduced the risk of death by half compared with chemotherapy alone.

More importantly, no matter the new combination may eventually show any additional efficacy, it needs to be powerful enough to be worthy of the additional toxicity brought by Lenvima.

Roy Baynes pointed out that the dose of Lenvima used in the LEAP-006 trial was lower than the LEAP-007 trial due to the toxicity of chemotherapy.

At least in the LEAP-007 trial, the combination of Keytruda+Lenvima without chemotherapy did not show any additional survival benefits for the non-squamous subgroup, and compared with Keytruda alone, the hazard ratio (HR) was 0.97.

In addition, the Phase 3 LEAP-008 trial is still enrolling patients. The trial will evaluate the Keytruda+Lenvima combination in second-line NSCLC patients who have previously received an anti-PD-1/L1 treatment and compare it with chemotherapy.

A Merck spokesperson confirmed to FiercePharma that the LEAP-006 and LEAP-008 trials are still in progress, and the end date is August 2023.

Reference:

Merck, Eisai’s 007 goes down as Keytruda-Lenvima combo fails in newly diagnosed lung cancer

Merck/Eisai “Immunity + Targeting” Combination for lung cancer failed

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