The following article features coverage from the Society of Immunotherapy of Cancer (SITC) 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Bempegaldesleukin (BEMPEG) plus nivolumab resulted in durable antitumor activity with high response rates among patients with treatment-naive metastatic melanoma, according to the results of a phase 1/2 trial presented at the virtual Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020).

BEMPEG is an agonist of the interleukin-2 signaling pathway that was previously reported to induce demonstrated antitumor activity among patients with metastatic melanoma in combination with nivolumab in the PIVOT-02 trial. The present report is of an updated analysis of the trial.

The phase 1/2 PIVOT-02 trial treated 41 patients with previously untreated metastatic melanoma and known programmed cell death ligand 1 (PD-L1) and BRAF status with BEMPEG plus nivolumab.

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During the phase 1 escalation portion, patients received increasing doses of BEMPEG with either 240 mg or 360 mg of nivolumab every 2 or 3 weeks. The recommended dose was 0.006 mg/kg of BEMPEG plus 360 mg of nivolumab every 3 weeks, which was used in the phase 2 dose-expansion phase. The coprimary endpoints were safety and tolerability and objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR), clinical benefit, and biomarkers.

At the time of the analysis, 38 of the 41 patients in the expansion cohort were evaluable for efficacy. Among this cohort, 58.5% had PD-L1–positive disease and 31.7% had a V600E or V600K BRAF mutation. Serum lactate dehydrogenase was normal among 70.7% of patients.

During a median follow-up of 29 months, the ORR was 53%, including 34% of patients who achieved a complete response. The ORR was 64% and 39% among patients whose disease was PD-L1–positive or –negative, respectively. These responses were durable, as 80% of patients had an ongoing response at data cutoff.

The median PFS was 30.9 months, with a rate of 56.2% at 12 months, 53.1% at 24 months, and 45.5% at 36 months. The median OS was not yet reached, but demonstrated a rate of 82.3%, 77%, and 70.9% at 12, 24, and 36 months, respectively.

Longer PFS was significantly associated with high levels of CD8-positive tumor-infiltrating lymphocytes (hazard ratio [HR], 5.18; 95% CI, 1.62-16.57; P =.0055) and a high interferon-γ gene-expression profile (HR, 4.15; 95% CI, 1.05-16.37; P =.0425) at baseline. These biomarkers were also associated with higher ORR. Tumor PD-L1 expression favored a higher ORR, but was not significant. There was no association between tumor mutational burden and blood-derived biomarkers with ORR.

There were no new safety signals in this analysis. The most common grade 3 to 4 treatment-related adverse events (TRAEs) were acute kidney injury (4.9%) and atrial fibrillation (4.9%). Treatment discontinuation of either BEMPEG or nivolumab occurred among 12.2% of patients due to TRAEs. No grade 5 AEs were reported.

Adi Diab, MD, of The University of Texas MD Anderson Cancer Center, and presenter of the study, concluded that “BEMPEG plus NIVO achieved deep and durable responses.” He noted that the regimen was recently granted a Breakthrough Therapy designation from the US Food and Drug Administration, and a phase 3 trial is now enrolling for patients with metastatic melanoma and in the adjuvant setting.

Disclosures: Research funding was provided by Idera, Nektar, Pfizer, Bristol Myers Squibb, and Apexigen. The presenters disclosed financial relationships with pharmaceutical companies; for a full list of disclosures, please refer to the original presentation.

Read more of Cancer Therapy Advisor‘s coverage of the SITC 2020 meeting by visiting the conference page.


Diab A, Tykodi SS, Daniels GA, et al. Progression-free survival and biomarker correlates of response with BEMPEG plus NIVO in previously untreated patients with metastatic melanoma: results from the PIVOT-02 study. Presented at: Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020); November 11-14, 2020. Abstract 420. J Immunother Cancer. 2020;8(Suppl 3):A656–A959.