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.

The combination of intratumoral NKTR-262 plus intravenous bempegaldesleukin (BEMPEG) demonstrated antitumor efficacy with an acceptable safety profile among patients with relapsed/refractory advanced solid tumors, according to the results of a phase 1 trial presented at the virtual Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020).

NKTR-262 is an intratumoral agent that enhances antigen presentation and sustained T-cell activation when combined with BEMPEG in preclinical studies. BEMPEG is a first-in-class interleukin-2 pathway agonist.

The REVEAL study treated 36 patients with relapsed or refractory advanced solid tumors in the phase 1 dose-escalation phase with increasing doses of NKTR-262 plus a fixed dose of BEMPEG. The dose-expansion phase of the phase ½ trial will assign patients to receive NKTR-262 plus BEMPEG or NKTR-262 plus BEMPEG and nivolumab.

The present analysis of phase 1 is on the endpoints that supported the selection of the phase 2 dose, including safety, pharmacokinetics, and biomarker data.


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Among the 28 patients evaluable for efficacy in the dose-escalation phase, tumor regression occurred in 29%. Among the 22 patients with melanoma, 9% of patients experienced an objective response, and the disease control rate was 41.2%.

There was 1 dose-limiting toxicity of transient grade 3 to 4 transaminase elevation in the highest NKTR-262 cohort. The maximum tolerated dose was not reached.

The most common treatment-related adverse events (TRAEs) for NKTR-262 monotherapy were flu-like symptoms, fatigue, and nausea. For the combination of NKTR-262 and BEMPEG, the most common TRAEs also included flu-like symptoms, fatigue, and nausea, as well as pruritus, rash, and vomiting.

Adi Diab, MD, of The University of Texas MD Anderson Cancer Center in Houston, Texas, and presenter of the study, concluded that “NKTR-262 intratumoral, as monotherapy or in combination, showed early signs of clinical activity and an acceptable safety profile in this highly relapsed/refractory melanoma patient population.”

The dose selected for the phase 2 study was 3.84 mg of intratumoral NKTR-262 plus 0.006 mg of intravenous BEMPEG.

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.

Reference

Diab A, Curti BD, Bilen MA, et al. REVEAL: Phase 1 dose-escalation study of NKTR-262, a novel TLR7/8 agonist, plus bempegaldesleukin: local innate immune activation and systemic adaptive immune expansion for treating solid tumors. Presented at: Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020); November 11-14, 2020. Abstract 368. J Immunother Cancer. 2020;8(Suppl 3):A656–A959.