Nektar and Bristol Myers Squibb’s NKTR-214/Opdivo Combination Granted FDA Breakthrough Therapy Designation for First-Line Treatment of Unresectable or Metastatic Melanoma

August 02, 2019 News /BioValleyBIOON/ -- Nektar Therapeutics and Bristol-Myers Squibb (BMS) recently jointly announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to the immunotherapy combination of bempegaldesleukin (BEMPEG, NKTR-214) and Opdivo (generic name: nivolumab) for the treatment of patients with previously untreated unresectable or metastatic melanoma. Currently, evaluating NKTR-214 in combination with Opdivo as first-line immunotherapy for advancedMelanomaThe Phase III clinical trial (NCT03635983) is currently recruiting patients.

Breakthrough Therapy Designation (BTD) is a new drug review pathway established by the FDA in 2012, aimed at accelerating the development and review of new drugs intended to treat serious or life-threatening diseases, where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies. Drugs granted BTD status can receive, during their development, includingFDACloser guidance, including from senior officials, to ensure that new treatment options are made available to patients in the shortest possible time.

FDAGranting of Breakthrough Therapy Designation (BTD) to the NKTR-214 + Opdivo immunotherapy combination is based on the ongoing Phase I/II clinical study PIVOT-02 in metastatic (Stage IV)MelanomaPatient cohort data, which were presented at the 2019 American ClinicalTumorpresented at the American Society of Clinical Oncology (ASCO) Annual Meeting.

The results showed that, as of March 29, 2019, with a median follow-up of 12.7 months, among 38 efficacy-evaluable patients receiving first-line treatment with the NKTR-214 plus Opdivo immunotherapy combination, the overall response rate (ORR) was 53% (20/38), the complete response rate (CR) was 34% (13/38), and the disease control rate (DCR: CR + PR + SD [complete response + partial response + stable disease]) was 74%. In the subgroups of patients with baseline PD-L1 negative status (n=14), PD-L1 positive status (n=21), unknown PD-L1 status (n=3), lactate dehydrogenase levels above the upper limit of normal (LDH > ULN, n=11), and liver metastases (n=10), the ORRs were 43%, 62%, 33%, 45%, and 50%, respectively.

Dr. Stephen Doberstein, Chief Research and Development Officer and Vice President of Research and Development at Nektar Therapeutics, stated, “In collaboration with our partner Bristol-Myers Squibb, we plan toFDACollaborate closely to continue advancing the development program of the NKTR-214 and Opdivo immunotherapy combination for the treatment of patients with advanced melanoma. We observed in the PIVOT-02 study that first-line treatment for advancedMelanomaEncouraged by the overall response rate data in patients. As the data from this cohort continue to mature, we look forward to future medicalConferencepublish the latest results.”

In September 2016, Bristol-Myers Squibb and Nektar Therapeutics entered into a clinical collaboration to evaluate the combination therapy of Opdivo and NKTR-214 for the treatment of various types of cancer. In February 2018, the two parties further reached a global strategic development and commercialization collaboration agreement worth up to $3.6 billion, jointly developing NKTR-214 in combination with Opdivo and Opdivo plus Yervoy for nine indications.TumorCombination applications in more than 20 types of indications, as well as combinations with other anticancer drugs from two companies or third parties. Currently, the NKTR-214/Opdivo immunotherapy combinationMelanomaand renal cell carcinoma (RCC) has entered Phase III clinical trials.

NKTR-214 is a CD122-biased IL-2 pathway agonist that stimulates the proliferation of anticancer immune cells in vivo by targeting the CD122-specific receptors present on the surface of natural killer (NK) cells, CD4+ T cells, and CD8+ T cells. CD122, also known as the interleukin-2 receptor beta subunit, is an important signaling receptor known to enhance the proliferation of these effector T cells. In preclinical and clinical studies, treatment with NKTR-214 has led to the rapid expansion of these cells and their mobilization into the tumor microenvironment.

Opdivo is a PD-1 immune checkpoint inhibitor designed to overcome immunosuppression, while NKTR-214 is an immunostimulatory therapy that has been shown to increase tumor-infiltrating cells, T-cell clonality, and PD-1 expression. Opdivo and NKTR-214 have two distinct, complementary mechanisms of action; their combination enhances the body’s immune system ability to combat cancer and has been demonstrated to convert baseline tumors from PD-L1 negative (<1%) to PD-L1 positive (≥1%).

It is crucial to augment the immune system by increasing the number of tumor-infiltrating lymphocytes (TILs) in the body, as many patients derive limited benefit from currently approved immune checkpoint inhibitors due to an insufficient TIL population. Combining immune checkpoint inhibitors with T-cell proliferation can produce a synergistic effect, thereby providing a new therapeutic option for patients.(Bio Valley Bioon.com)

Original Source:Nektar Therapeutics