ARTISTRY-1: Nemvaleukin alfa monotherapy and in combination with pembrolizumab in patients (pts) with advanced solid tumors.

Abstract

2513 Background: Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel, engineered cytokine that selectively binds the intermediate-affinity interleukin-2 (IL-2) receptor complex to preferentially activate CD8+ T cells and natural killer cells with minimal expansion of regulatory T cells, designed to leverage antitumor effects of the IL-2 pathwaywhile mitigating potential toxicity that would limit use. Methods: ARTISTRY-1 (NCT02799095) is a phase 1/2 study. Parts A (dose escalation 0.1-10 µg/kg) and B (6 µg/kg [recommended phase 2 dose]) are monotherapy; pts receive intravenous nemvaleukin for 5 days every 14 or 21 days. In Part C, pts receive nemvaleukin (3 or 6 µg/kg) every 21 days in combination with pembrolizumab (200 mg on day 1). We present safety and antitumor activity (RECIST v1.1, iRECIST) data as of 12/02/2020. Results: In Part A, 39 pts received nemvaleukin. No dose-limiting toxicities were observed; maximum tolerated dose was not reached. Part B enrolled immune checkpoint inhibitor–pretreated pts into melanoma or renal cell carcinoma (RCC) cohorts. 18 pts with melanoma enrolled; 10 were evaluable, 2 (both with metastatic mucosal melanoma) achieved a partial response (PR; 1 unconfirmed). 24 pts with RCC enrolled; 1 of 16 evaluable pts achieved a PR (awaiting confirmation). 12 pts in each cohort continue on study. In Parts A and B, treatment-related adverse events in ≥40% included chills (74.4% and 52.4%, respectively) and pyrexia (74.4% and 47.6%, respectively). In Part C (83 evaluable pts), 12 objective responses (OR) were observed; an additional 5 pts had stable disease (SD) >6 months (1 pt with breast cancer, 2 with ovarian cancer, and 2 with non-small-cell lung cancer). Nemvaleukin did not demonstrate any additive toxicity to that already established with pembrolizumab alone. OR data are summarized in the table. Conclusions: Nemvaleukin was generally well tolerated and demonstrated antitumor activity as monotherapy and in combination with pembrolizumab. Pharmacodynamic studies to identify biomarkers are ongoing. Future research of monotherapy and combination therapy with nemvaleukin is warranted. Clinical trial information: NCT02799095. [Table: see text]

Double Trouble: Immunotherapy Doublets in Melanoma—Approved and Novel Combinations to Optimize Treatment in Advanced Melanoma

“…120 Preliminary data from an ongoing phase I/II clinical trial (NCT02799095) suggest that nemvaleukin is generally well tolerated and demonstrates efficacy, both as monotherapy and in combination with anti-PD-1, with 3 of 28 patients thus far responding to the treatment (including patients with at least one available scan). 121 Of note, treatment response was observed in two patients with mucosal melanoma, thereby granting fast-track U.S. Food and Drug Administration designation for this indication. 122 Similarly, bempegaldesleukin (BEM-PEG; NKTR-214) is a CD122-preferential IL-2 agonist that selectively binds to the IL-2 receptor b.…”

Next Wave of Targets in the Treatment of Advanced Renal Cell Carcinoma

“…Among 16 evaluable patients with RCC, one patient achieved a partial response with monotherapy. The toxicity profile was found to be acceptable, with the most common TRAEs including chills and pyrexia [ 75 ]. The combination phase of this trial is ongoing (NCT03861793).…”

New clinical developments in drug therapy for ovarian cancer: results of the annual congress «Cancer in women» 2022

“…В связи с этим было запланировано исследование SORAYA, подтвердившее эффективность мирветуксимаба соравтансина среди пациенток с высокой экспрессией FRα. Кроме того, ответ на лечение в исследовании SORAYA оказывался лучше, чем, например, в исследовании AURELIA 8 , в котором изучалась эффективность бевацизумаба при платина-резистентном РЯ (частота ответа 32% по сравнению с 12% соответственно). В настоящее время проводится рандомизированное исследование MIRASOL фазы III 9 , в отличие от одногруппового дизайна в исследовании SORAYA с включением больных РЯ и высокой экспрессией FRα.…”

“…URL: https://www.clinicaltrials.gov/ct2/show/ NCT04296890?term=SORAYA&draw=2&rank=1 (дата обращения 04.05.2022). 8 National Library of Medicine. AURELIA: A study of avastin (bevacizumab) added to chemotherapy in patients with platinum-resistant ovarian cancer.…”