Nektar Therapeutics and BMS Secure Chinese IND Approval for NKTR-214 (Bempegaldesleukin) in Combination with Nivolumab for First-Line Treatment of Advanced or Metastatic Renal Cell Carcinoma

On April 16, NKTR-214, co-developed by Nektar Therapeutics and Bristol-Myers Squibb (BMS), received clinical trial approval in China for use in combination with nivolumab injection for the treatment of previously untreated patients with advanced or metastatic renal cell carcinoma. This marks the first clinical trial approval for NKTR-214 in China.

NKTR-214 is an inactive prodrug formed by attaching six polyethylene glycol (PEG) moieties to the native interleukin-2 (IL-2) molecule. Upon administration, these PEG groups are gradually cleaved, generating active species with two or one PEG attachments (2-PEG and 1-PEG forms), thereby extending the half-life to 10 hours. Furthermore, NKTR-214 exhibits reduced binding affinity for both the alpha chain (CD25) and beta chain (CD122) of the IL-2 receptor; however, the reduction in affinity for CD25 is more pronounced. This results in greater selectivity for CD122 activation, preferentially stimulating CD8+ T cells rather than regulatory T cells (Tregs). This mechanism effectively mitigates severe toxic side effects and prolongs the duration of action, forming the basis for its combination therapy with PD-1 inhibitors.

In September 2016, Bristol-Myers Squibb (BMS) and Nektar Therapeutics entered into a clinical collaboration to evaluate the efficacy and safety of the combination therapy of NKTR-214 plus Opdivo for various types of cancer. In February 2018, the two companies further reached a global strategic development and commercialization agreement valued at $3.6 billion, jointly developing NKTR-214 in combination with Opdivo and Opdivo plus Yervoy for more than 20 indications across nine tumor types. In August 2019, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to the NKTR-214 plus Opdivo combination regimen for the treatment of melanoma.

Source: PharmaCube NextPharma

In November 2018, Nektar Therapeutics entered into a clinical collaboration with Pfizer to jointly evaluate the efficacy of NKTR-214 in combination with avelumab, talazoparib, or enzalutamide for the treatment of various cancers, including metastatic castration-resistant prostate cancer (mCRPC) and squamous cell carcinoma of the head and neck (SCCHN).

In addition, Nektar Therapeutics also plans to conduct combination studies of NKTR-214 with cell therapies and vaccines.