ORR Reaches 60%! BMS/Nektar Immuno-Oncology Combination Demonstrates Robust Efficacy Across Multiple Solid Tumors

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Recently, data from the Phase I clinical trial (PIVOT-02; NCT02983045) evaluating the combination of Nektar Therapeutics’ lead immuno-oncology candidate bempegaldesleukin (bempeg, NKTR-214) and Bristol-Myers Squibb’s PD-1 therapy Opdivo (nivolumab) for the treatment of solid tumors were published in the American Association for Cancer Research journal Cancer Discovery.

This dose-escalation study was conducted in 38 patients with advanced solid tumors, including melanoma, renal cell carcinoma, and non-small cell lung cancer, who had not previously received immunotherapy. Reported herein are the results regarding safety, immune activation, and efficacy.

Data show that bempeg combined with Opdivo increased T-cell infiltration into the tumor microenvironment, enhanced PD-L1 expression during treatment, and achieved encouraging response rates. Equally important, data indicate no increase in the inflammatory T-cell subset Th-17, which plays a key role in modulating typical immune-related adverse events associated with checkpoint inhibitors.

The main findings of this study are summarized as follows:

Bempeg 0.006 mg/kg Q3W (every 3 weeks) and Opdivo 360 mg Q3W were established as the recommended Phase 2 dose (RP2D);

Adverse events observed in the study were manageable, generally transient and reversible;

Combination therapy increased the absolute counts and proliferation of peripheral blood CD8+ T cells and NK cells, and upregulated the expression of immune activation–associated genes in the tumor microenvironment;

Combination therapy has demonstrated encouraging overall response rates (ORR) across multiple tumor types, independent of PD-L1 expression. Responses continued to deepen over time.

The specific efficacy data were as follows: the overall response rate (ORR) was 59.5%, the complete response (CR) rate was 18.9%, and the disease control rate (DCR) was 83.8%. In PD-L1-positive and PD-L1-negative patients, the ORRs were 64.7% and 50.0%, respectively. Among the 22 patients with confirmed objective responses, the median time from treatment initiation to response was 1.9 months (range: 1.3–7.8), and the median duration of response had not yet been reached.

Currently, although checkpoint inhibitors are effective in various types of tumors, only a small proportion of patients achieve durable responses. Bempeg combined with Opdivo demonstrates favorable tolerability and induces meaningful tumor and immune responses across multiple types of solid tumors. Furthermore, this combination exhibits significant clinical activity independent of baseline PD-L1 status, with deepening responses observed as treatment cycles progress.

Bempeg is an investigational, first-in-class, CD122-biased IL-2 pathway agonist that rapidly activates and expands anticancer immune cells—namely, CD8+ effector T cells and natural killer (NK) cells—without excessive activation of the immune system. This therapy aims to stimulate these anticancer immune cells in vivo by targeting the CD122-specific receptors found on their surface. CD122, also known as the interleukin-2 receptor beta subunit, is a key signaling receptor known to enhance the proliferation of these effector T cells. In preclinical and clinical studies, bempeg treatment has been shown to induce rapid proliferation of these cells and their mobilization into the tumor microenvironment. Bempeg features a dosing regimen similar to that of approved checkpoint inhibitor antibody drugs.

Opdivo is designed to overcome immunosuppression, while bempeg aims to stimulate the immune system and has been shown to increase tumor-infiltrating cells, T-cell proliferation, and PD-L1 expression. The two agents have complementary mechanisms of action, and their combination enhances the body’s immune response against cancer. This regimen has been demonstrated to convert baseline tumors from PD-L1 negative (<1%) to PD-L1 positive (≥1%).

The collaboration between BMS and Nektar began in 2016, and the two parties reached a global strategic development and commercialization agreement worth $3.6 billion in 2018. In January this year, they revised their cooperation agreement to expand the clinical projects of the bempeg+Opdivo combination.

Currently, the combination is being evaluated in multiple Phase II and registrational Phase III trials, including those for metastatic melanoma, muscle-invasive bladder cancer, metastatic urothelial carcinoma ineligible for cisplatin-based chemotherapy, and metastatic renal cell carcinoma.

Reference Source:

1、Nktar Therapeutics Announces Publication of Results from Phase 1 Dose-Escalation Study for Bempegaldesleukin Plus Nivolumab in 'Cancer Discovery' Journal

2、Nektar Therapeutics and Bristol-Myers Squibb Amend Strategic Collaboration Agreement for bempegaldesleukin Plus Opdivo (nivolumab)