Bempegaldesleukin-Opdivo Combo Leads to Prolonged Responses in TNBC Patients, Phase 1/2 Trial Shows

Bempegaldesleukin (bempeg, NKTR-214) in combination with Opdivo (nivolumab) leads to prolonged treatment responses in women with advanced or metastatic triple-negative breast cancer (TNBC), a Phase 1/2 trial shows.

The findings were presented in a poster titled, “Clinical activity of BEMPEG plus NIVO observed in metastatic TNBC: preliminary results from the TNBC cohort of the Ph1/2 PIVOT-02 study,” at the 2019 CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference, held Sept. 25-28 in Paris.

Bempegaldesleukin, developed by Nektar Therapeutics, is an investigational first-in-class agent that targets CD122, a protein found on the surface of immune T cells and natural killer (NK) cells. It works by activating and stimulating the growth of these cancer-killing immune cells, without over-activating the entire immune system.

PIVOT-02 (NCT02983045) is a multi-center, open-label, Phase 1/2 trial that is assessing the safety and efficacy of bempegaldesleukin in combination with Opdivo, an immune checkpoint inhibitor developed by Bristol-Myers Squibb, in patients with different types of solid cancers, including breast cancer.

The study is divided into two phases: a dose escalation phase, in which patients with different types of solid cancers will be assigned to one of five different bempegaldesleukin-Opdivo combo regimens to determine the best dose and scheduling interval for each of the medications; and a dose expansion phase, in which patients with different types of solid cancers will receive bempegaldesleukin in combination with Opdivo at the best dose and scheduling interval determined during the dose escalation phase.

During the conference, Nektar presented the first findings of the group of women with TNBC participating in the dose expansion phase of PIVOT-02.

At the time of data cut-off (July 1), 38 women with advanced or metastatic TNBC who received bempegaldesleukin at a dose of 0.006 mg/kg every three weeks in combination with Opdivo at a dose of 360 mg every three weeks — the recommended dose — were eligible for treatment efficacy assessments.

These patients had at least one poor prognostic feature (e.g., high number of metastases, early relapse, or PD-L1 negative tumor), but five of them (13%) responded favorably to the combination therapy.

All five women had previously received at least one course of chemotherapy after their cancer had spread to other areas before enrolling in the study. Three of them also had PD-L1 negative tumors, which are normally harder to treat with checkpoint inhibitors or chemotherapy agents, at the beginning of the study.

One of the woman who responded favorably discontinued therapy after 20.7 months when she had 100% reduction of her target lesions and reached a point of maximal clinical benefit. The four remaining women are still receiving treatment and continue showing prolonged responses to therapy.

Almost half the women who were eligible for efficacy assessments (45%) had either a complete response (complete cancer eradication), partial response (partial cancer eradication), or achieved a state of stable disease during treatment.

The bempegaldesleukin-Opdivo combo was generally well-tolerated by patients. Treatment-related adverse events reported during the study were consistent with previous studies.

Approximately a fourth of the women (26%) reported severe (grade 3) or life-threatening (grade 4) adverse events, and two had to stop treatment prematurely due to treatment-related adverse events. The most common severe and life-threatening events included dehydration (4.7%), low blood pressure (4.7%), and muscle pain (4.7%).

“The data presented today in patients with metastatic TNBC demonstrate the promising clinical activity of bempeg plus nivolumab, most notably in patients with PD-L1-negative baseline tumors,” Mary Tagliaferri, MD, chief medical officer at Nektar Therapeutics, said in a press release.

“Responses were prolonged and occurred in patients with multiple negative predictive factors for clinical benefit with a checkpoint inhibitor, including prior treatment with taxane therapy and multiple sites of metastases. These data support potential future development of this doublet in combination with chemotherapy in the population of TNBC patients with the highest unmet medical need,” Tagliaferri said.