Pembrolizumab monotherapy as first-line therapy in advanced clear cell renal cell carcinoma (accRCC): Results from cohort A of KEYNOTE-427.
Bibliographic record
Abstract
4500 Background: Programmed death-1 (PD-1) inhibitor–based combination therapy shows clinical benefit in first-line accRCC. However, data are limited on clinical impact of first-line PD-1 inhibitor monotherapy. KEYNOTE-427 (NCT02853344) is a single-arm, open-label, 2-cohort, phase 2 study that evaluates efficacy and safety of the PD-1 inhibitor pembrolizumab (pembro) as first-line monotherapy in accRCC and anccRCC. Results from the accRCC cohort (cohort A) are presented. Methods: Patients (pts) with histologically confirmed accRCC who received no prior systemic therapy were eligible. Additional key eligibility criteria included measurable disease (RECIST v1.1, independent central review [ICR]) and Karnofsky performance status ≥70%. Pembro 200 mg was administered intravenously Q3W for 2 y or until confirmed progressive disease, unacceptable toxicity, or pt decision to withdraw. Primary end point: objective response rate (ORR) per RECIST v1.1, ICR. Additional end points included duration of response, safety, and biomarkers associated with response. Results: At data cutoff (Oct 6, 2017), median (range) follow-up was 7.2 (0.9-11.7) mo. 110 pts were enrolled; 107 included in the efficacy analysis (opportunity for ≥1 postbaseline assessment). Median age (range) was 64 (29-87); 78% were male. 37.3%, 47.3%, and 15.5% of pts had IMDC risk categories of favorable, intermediate, and poor, respectively. Confirmed ORR by ICR was 33.6% (n = 36; 95% CI, 24.8-43.4) with 1 complete response (0.9%) and 35 (32.7%) partial responses. ORR for pts with favorable, intermediate/poor risk IMDC was 27.5% and 37.3%, respectively. Median duration of response was not reached (range, 1.4+ to 8.2+). 73.6% of pts experienced a treatment-related adverse event (AE); most common (≥10%) were fatigue (23.6%), pruritus (21.8%), diarrhea (16.4%), rash (13.6%), and arthralgia (11.8%). 18.2% experienced a grade 3-5 treatment-related AE; 1 patient had grade 5 pneumonitis. Conclusions: Pembro monotherapy demonstrated promising efficacy and acceptable tolerability in pts with accRCC. Potential tissue-based biomarkers associated with response will be presented. Clinical trial information: NCT02853344.
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".