First-line pembrolizumab plus lenvatinib for non–clear cell renal carcinomas (nccRCC): Extended follow-up of the phase 2 KEYNOTE-B61 study.
Bibliographic record
Abstract
2 Background: Pembrolizumab (pembro) + lenvatinib (lenva) is approved for first-line treatment of advanced/metastatic RCC based on results of the phase 3 KEYNOTE-581/CLEAR study. Previously reported results from the phase 2 KEYNOTE-B61 (NCT04704219) study with a median follow-up of 15 months further support the use of pembro + lenva in the first-line setting specifically across nccRCC. We now report updated results from KEYNOTE-B61 with median follow-up of 23 months. Methods: Adults with previously untreated, advanced nccRCC (histology assessed by investigator) and measurable disease per RECIST v1.1 received pembro 400 mg IV Q6W for ≤18 cycles (~2 years) + lenva 20 mg orally once daily until intolerable toxicity, progressive disease, or patient (pt) withdrawal from the study. Primary end point was ORR per RECIST v1.1 by blinded independent central review (BICR). Secondary end points included DCR, DOR, and PFS per RECIST v1.1 by BICR, OS, and safety. Results: A total of 158 pts received pembro + lenva. Median age was 60 years (range, 24-87), and the most common histologic variants of RCC were papillary (n = 93; 59%), chromophobe (n = 29; 18%), and unclassified (n = 20; 13%). Median time from first dose to the data cutoff date of July 5, 2023, was 22.8 months (range, 16.6-27.6). 86 pts had discontinued treatment (most commonly due to progressive disease, n = 56 [35%]). In all pts, ORR was 51% (95% CI, 43-59; 13 CRs [8%]; 67 PRs [42%]) and DCR was 82% (95% CI, 75-88). Median DOR was 19.5 months (range, 15.3-not reached [NR]). An estimated 51% of responses had a duration of ≥18 months. ORR and DCR by histology are shown in the table. In all pts, median PFS and OS were 17.9 months (95% CI, 15.1-22.1) and NR (95% CI, NR-NR); estimated 18-month PFS and OS rates were 48% and 73%. Treatment-related AEs (TRAEs) occurred in 151 pts (96%), most commonly hypertension (56%), diarrhea (46%), hypothyroidism (41%), and proteinuria (30%). Grade 3-4 TRAEs occurred in 92 pts (58%), most commonly hypertension (25%), and diarrhea, proteinuria, and decreased weight (5% each). No deaths due to TRAEs were reported. Discontinuation due to TRAEs for pembro, lenva, or both pembro and lenva occurred in 15%, 13% and 4% of pts, respectively. Conclusions: Consistent with prior reports, pembro + lenva had durable antitumor activity and a manageable safety profile in pts with advanced nccRCC. These results continue to support pembro + lenva as a first-line treatment option for pts with variant histologies of nccRCC. Clinical trial information: NCT04704219 . [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 | 0.004 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| 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".