Nemvaleukin alfa monotherapy and in combination with pembrolizumab in patients (pts) with advanced solid tumors: ARTISTRY-1.
Bibliographic record
Abstract
2500 Background: Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel, engineered cytokine that selectively binds to the intermediate-affinity interleukin-2 (IL-2) receptor (IL-2R) to preferentially activate antitumor CD8+ T cells and natural killer (NK) cells with minimal expansion of immunosuppressive regulatory T cells. It is sterically occluded from binding to the high-affinity IL-2R, leveraging antitumor effects of the IL-2 pathway but mitigating toxicity associated with preferential binding of IL-2 to the high-affinity IL-2R. Methods: ARTISTRY-1 (NCT02799095) is a 3-part, first-in-human, phase 1/2 study of IV nemvaleukin alone and in combination with pembrolizumab in pts with advanced solid tumors. Parts A (dose escalation to 10 µg/kg/day), B (monotherapy in pts with melanoma or renal cell carcinoma [RCC]), and C (combination) included nemvaleukin 3 or 6 µg/kg/day ´ 5 and pembrolizumab every 21 days. Investigator-assessed antitumor activity (confirmed responses as per RECIST v1.1) and safety are reported as of 29 October 2021. Results: In Part A (N = 46), nemvaleukin recommended phase 2 dose was 6 µg/kg/day IV; maximum tolerated dose not reached. One pt had dose-limiting toxicity (grade 4 acute kidney injury) at 10 µg/kg. Pts in Parts B and C were heavily pretreated (1–9 prior lines of therapy, including prior checkpoint inhibitor therapy). Durable antitumor activity was observed for nemvaleukin monotherapy, including in RCC (objective response rate [ORR], 18.2% [4/22]) and in melanoma (ORR, 8.7% [4/46]), with 2 partial responses (1 unconfirmed) in 30 pts with cutaneous melanoma (ORR, 6.7%) and 2 PRs (1 unconfirmed) in 6 pts with mucosal melanoma (ORR, 33.3%). Durable antitumor activity was also observed for combination therapy (ORR, 16.1% [22/137]; disease control rate [DCR], 59.9%), including in platinum-resistant ovarian cancer (PROC; ORR, 28.6% [4/14]; DCR, 71.4%), with 2 complete responses and 2 PRs (1 unconfirmed) in 14 pts. Forty-three pts remain on therapy. The most frequent grade 3/4 treatment-related adverse events in Parts B and C, respectively, were anemia (9%, 10%), neutropenia (34%, 9%), and decreased neutrophil count (12%, 9%). Safety was consistent with previous reports. In pharmacodynamic studies, nemvaleukin monotherapy induced robust expansion of CD8+ T and NK cells, with minimal effect on regulatory T cells. Conclusions: ARTISTRY-1 showed proof of principle for preferential expansion of CD8+ T cells and NK cells by nemvaleukin. Nemvaleukin was generally well tolerated and demonstrated promising efficacy. Durable responses were observed with monotherapy and combination therapy in heavily pretreated pts across a range of tumors, warranting further investigation. The US FDA granted nemvaleukin Fast Track designation for treatment of mucosal melanoma and PROC, and Orphan Drug designation for mucosal melanoma. Clinical trial information: NCT02799095.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".