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

2021· article· en· W3172376856 on OpenAlexaff
Valentina Boni, Ira Winer, Lucy Gilbert, Ulka N. Vaishampayan, Seth Rosen, Jameel Muzaffar, Anna Spreafico, David F. McDermott, Quincy S. Chu, Olivier Dumas, Aman Chauhan, Arvind Chaudhry, Piotr Tomczak, Débora S. Bruno, Yangchun Du, Ilda Bidollari, Jessicca Rege, Marc S. Ernstoff, James Strauss, Vamsidhar Velcheti

Bibliographic record

VenueJournal of Clinical Oncology · 2021
Typearticle
Languageen
FieldMedicine
TopicCancer Immunotherapy and Biomarkers
Canadian institutionsCentre hospitalier universitaire de QuébecPrincess Margaret Cancer CentreUniversity of TorontoUniversity Health NetworkRoyal Victoria HospitalMcGill University Health CentreUniversity of AlbertaRoyal Victoria Regional Health Centre
Fundersnot available
KeywordsMedicinePembrolizumabChillsInternal medicineMelanomaRenal cell carcinomaAdverse effectResponse Evaluation Criteria in Solid TumorsTolerabilityGastroenterologyAldesleukinToxicityOncologyPhases of clinical researchSurgeryInterleukin 2CytokineImmunotherapyCancerCancer research

Abstract

fetched live from OpenAlex

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]

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Non-randomized trial · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.034
GPT teacher head0.394
Teacher spread0.360 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNon-randomized trial
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations10
Published2021
Admission routes1
Has abstractyes

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