Cemiplimab and Talazoparib Head Toward Approval in the EU

Roxanne Nelson, RN, BSN

April 29, 2019

The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended granting a conditional marketing authorization for cemiplimab (Libtayo, Regeneron Pharmaceuticals and Sanofi) for the treatment of advanced cutaneous squamous cell carcinoma (CSCC). The conditional approval is for adult patients with metastatic or locally advanced CSCC who are not candidates for curative surgery or curative radiotherapy.

The CHMP has also given a positive opinion for talazoparib (Talzenna, Pfizer) for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer. To be eligible for treatments, patients should have previously undergone treatment with an anthracycline or a taxane in the neoadjuvant setting for locally advanced or metastatic disease unless they were not suitable candidates for those therapies.

Both drugs are already approved in the United States for similar indications.

First Treatment for Certain Skin Cancers

Cemiplimab is a fully human monoclonal antibody that targets the immune checkpoint receptor PD-1 pathway. It received approval by the US Food and Drug Administration (FDA) last September for the same indications. It is the first FDA-approved drug specifically for advanced CSCC, and it will also be the only treatment approved for certain patients with advanced CSCC in the European Union.

"This type of cancer can be difficult to treat effectively when it is advanced, and it is important that we continue to bring new treatment options to patients," commented Richard Pazdur, MD, director of the FDA's Oncology Center of Excellence, when the drug was approved in the United States.

The CHMP's positive opinion was based on data from the pivotal, multicenter, nonrandomized phase 2 EMPOWER-CSCC-1 trial and was supported by two advanced CSCC expansion cohorts from a multicenter phase 1 trial. Together, these trials provide the largest prospective dataset of advanced CSCC patients.

In the EMPOWER study, a response was observed in 28 of 59 patients (47%) who received cemiplimab, at a median follow-up of 7.9 months. Among those who achieved a response, the duration exceeded 6 months in 57%, and 82% continued to have a response and to receive cemiplimab at the time of data cutoff.

Cemiplimab is being jointly developed by Sanofi and Regeneron under a global collaboration agreement. As part of the conditional approval, the manufacturers are required to provide additional data from EMPOWER-CSCC-1 study, including results from a group that was newly added to the trial, to further confirm the benefit-risk profile. The European Commission is expected to make a final decision on the application in the coming months.

Cemiplimab is also being investigated in potential registrational trials in non–small cell lung cancer, basal cell carcinoma, and cervical cancer, as well as in additional trials in squamous cell carcinoma of the head and neck, melanoma, colorectal cancer, prostate cancer, multiple myeloma, Hodgkin lymphoma, and non-Hodgkin lymphoma.

New Option for BRCA+ Breast Cancer

Talazoparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, received approval by the FDA in October 2018. It is indicated for patients with deleterious or suspected deleterious germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer. Patients must be selected for therapy on the basis of an FDA-approved companion diagnostic for talazoparib.

The CHMP positive opinion was granted after a review of the results from the EMBRACA trial, the largest phase 3 trial to date with a PARP inhibitor involving patients with BRCA-mutated locally advanced or metastatic breast cancer. Talazoparib was compared to physician's choice standard chemotherapy (capecitabine, eribulin, gemcitabine or vinorelbine) for patients with an inherited BRCA1/2 mutation and triple-negative or HR+/HER2 disease who may have received up to three prior cytotoxic chemotherapy regimens for their advanced disease. A total of 431 patients were enrolled at 145 sites in 16 countries.

Progression-free survival, which was the primary endpoint, was 46% longer for patients in the talazoparib arm than for those in the comparator arm, at 8.6 months vs 5.6 months (P < .001).

In addition, 37% of patients treated with the PARP inhibitor experienced disease progression or death at 1 year, compared with 20% of patients in the other arm. The response rate to the PARP inhibitor was also numerically higher, at 62.6% vs 27.2%.

"There is a pressing need for new, effective medicines that are specifically developed for patients with an inherited BRCA mutation, who are often diagnosed at a younger age and have limited options for the treatment of advanced-stage disease," said Chris Boshoff, MD, PhD, chief development officer for oncology, Pfizer Global Product Development, in a statement. "Results from the EMBRACA trial provide evidence supporting the use of talazoparib in these patients, and we look forward to working with the European Commission to potentially offer an alternative treatment option to chemotherapy."

The company notes that talazoparib is being evaluated in several ongoing clinical trials in breast cancer and other cancers, including early triple-negative breast cancer and prostate cancer. It is also being evaluated in novel combinations with targeted therapies and with immunotherapy in various solid tumors.

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