Phase II study of recombinant IL-21 (rIL-21) plus sorafenib as second- or third-line therapy for metastatic renal cell cancer (mRCC): Final results
Bibliographic record
Abstract
3023 Background: Despite the positive impact of targeted therapies on treatment for mRCC, the efficacy of these agents appears to decrease beyond the first-line setting. There is an unmet need for novel therapies after failure of vascular endothelial growth factor (VEGF)-directed agents. rIL-21, a cytokine that enhances CD8+ T-cell and NK cell activity, has single-agent antitumor activity (J Clin Oncol. 2008;26:2034). Based on promising results of a phase I study of rIL-21 plus sorafenib, we initiated a phase II study to explore the safety and efficacy of this combination as second- or third-line treatment for mRCC. Methods: Patients with mRCC received second- or third-line therapy with sorafenib 400 mg PO BID continuously plus rIL-21 30 μg/kg IV on days 1–5 and 15–19 of each 7-week treatment course (TC). Efficacy endpoints included progression-free survival (PFS) and overall response rate (ORR) per RECIST. Response was assessed by the investigator and by independent radiologic review (IRR). Results: 33 patients were enrolled from 14 sites in the U.S. and Canada. Median age was 61 years (range, 46–75); ECOG performance status was 0 (n=15) or 1 (n=18). Patients had received 1 (n=25) or 2 (n=8) prior lines of therapy, including sunitinib (n=19), temsirolimus (n=5), bevacizumab (n=3), everolimus (n=2), IL-2 (n=11), or other (n=4). Grade ≥3 adverse events considered at least possibly related to study drug and occurring in ≥3 patients included hypophosphatemia (33%), hand-foot syndrome (24%), rash (24%), thrombocytopenia (8%), and neutropenia (8%). Twelve patients remain on study; 13 withdrew for progressive disease (PD), 6 for toxicity, and 2 for other reasons. IRR has been performed for the first 23 patients who completed at least 1 full TC, with 6 confirmed PR (26%), 1 unconfirmed PR (4%), 14 SD (61%), and 2 PD (9%). While median PFS cannot yet be determined, 14 of the first 29 patients have completed at least 3 TCs, equivalent to approximately 21 weeks, with SD or better. Conclusions: rIL-21 plus sorafenib is associated with an acceptable safety profile and promising antitumor efficacy in previously treated patients with mRCC. The observed ORR to date compares favorably with the rate previously reported for sorafenib in the first and second-line setting. [Table: see text]
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 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".