Nektar Therapeutics and BMS Report 53% Overall Response Rate with NKTR-214 Plus Opdivo in First-Line Metastatic Melanoma

Nov 13, 2019 17:10 CST Updated 17:10

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Society for Immunotherapy of Cancer

The Society for Immunotherapy of Cancer (SITC) is an organization dedicated to advancing science and cancer immunotherapy. As a 501(c)(3) non-profit medical professional association, it comprises influential research scientists, physician-scientists, clinicians, patients, patient advocates, government representatives, and industry leaders. SITC is committed to improving the efficacy of cancer immunotherapy for patients by advancing scientific knowledge and its application. Through educational programs that foster scientific exchange and collaboration, SITC aims to one day make “cure” a reality for cancer patients worldwide.

Bristol-Myers Squibb (BMS) partner Nektar Therapeutics recently presented the latest data from the Phase I/II PIVOT-02 study on the first-line treatment of patients with metastatic (Stage IV) melanoma using the immunotherapy combination of bempegaldesleukin (BEMPEG, NKTR-214) and Opdivo (generic name: nivolumab) at the 2019 Society for Immunotherapy of Cancer (SITC) Annual Meeting.

Data as of September 25, 2019 showed: (1) With a median follow-up of 18.6 months, among efficacy-evaluable patients (n=38), the confirmed objective response rate (ORR) was 53% (20/38), and the complete response rate (CR) was 34% (13/38). Forty-two percent (16/38) of patients achieved a 100% reduction in target lesions. The disease control rate (DCR: complete response + partial response + stable disease) was 74% (28/38). (2) The median time to response was 2.0 months, and the median time to complete response was 7.9 months. (3) The median reduction in target lesions from baseline was 61.5%. (4) At a median follow-up of 18.6 months, the median duration of response (DOR) had not been reached, with 85% (17/20) of responders maintaining their response. (5) Among 35 patients with known baseline PD-L1 status, the ORRs were 39% (5/13) in PD-L1-negative patients and 64% (14/22) in PD-L1-positive patients. (6) At a median follow-up of 18.6 months, the median progression-free survival (PFS) had not been reached (95% CI: 5.3–NE). (7) The combination of BEMPEG + Opdivo was well tolerated, with treatment-related adverse events being predictable and transient.

In August 2019, Bristol-Myers Squibb (BMS) and Nektar Therapeutics announced that the U.S. FDA had granted Breakthrough Therapy Designation (BTD) to the combination therapy of BEMPEG plus Opdivo for the treatment of patients with previously untreated unresectable or metastatic melanoma. Currently, the Phase III study (NCT03635983) evaluating the BEMPEG plus Opdivo combination versus Opdivo as first-line treatment in patients with advanced melanoma is enrolling participants.

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 agreement valued at up to $3.6 billion, jointly developing the combination of NKTR-214 with Opdivo and Opdivo plus Yervoy across more than 20 indications in nine tumor types, as well as combinations with other anticancer agents from two companies or third parties. Currently, the NKTR-214/Opdivo immunotherapy combination for the treatment of melanoma and renal cell carcinoma (RCC) has entered Phase III clinical trials.

Bempegaldesleukin (NKTR-214) Can Stimulate the Proliferation of Anti-Cancer Immune Cells

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 demonstrated to increase tumor-infiltrating cells, T-cell clonality, and PD-1 expression. Opdivo and NKTR-214 have two distinct and complementary mechanisms of action; their combination enhances the body’s immune system capacity to combat cancer. This regimen has been proven to convert baseline tumors from PD-L1 negative (<1%) to PD-L1 positive (≥1%).

Increasing the number of tumor-infiltrating lymphocytes (TILs) in the body to bolster the immune system is crucial, as many patients lack sufficient TIL populations and therefore struggle to benefit from currently approved immune checkpoint inhibitors. Combining immune checkpoint inhibitors with T-cell proliferation can produce synergistic effects, thereby offering patients a new therapeutic option.

Original Source:

1、Nektar Therapeutics Presents New Clinical and Preclinical Data from its Immuno-Oncology Pipeline at the 2019 Society for Immunotherapy of Cancer (SITC) Annual Meeting

2、Clinical activity of BEMPEG plus NIVO in previously untreated patients with metastatic melanoma: updated results from the Phase 1/2 PIVOT-02 Study

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