Evaluation of immune-related response criteria (irRC) in patients (pts) with advanced melanoma (MEL) treated with the anti-PD-1 monoclonal antibody MK-3475.
Bibliographic record
Abstract
3006^ Background: Unique response patterns have been observed with immunotherapies, and both objective response and prolonged disease stabilization can occur after an initial increase in tumor size. irRC were developed to better characterize response to immunotherapy, but it is unclear how irRC perform in pts treated with PD-1 blockade. Here, we describe unique patterns of response to MK-3475 in MEL pts and evaluate irRC as an alternative criterion for comprehensive response assessment. Methods: Source population was pts from 3 MEL cohorts treated with MK-3475 2 mg/kg every 3 wk (Q3W), 10 mg/kg Q3W, or 10 mg/kg Q2W in a phase I trial. Tumor imaging was performed every 12 wk. Response was assessed by irRC and RECIST 1.1 by central review; irRC was used for pt management. Tumor flare and atypical delayed response were identified by using centrally assessed irRC data among pts on MK-3475 for ≥28 wk. Tumor flare was defined as unconfirmed PD at assessment 1 (ie, wk 12) and non-PD at assessment 2. Atypical delayed response was defined as PD at any time point followed by non-PD and then response. Survival data were analyzed in pts who had PD by RECIST but CR/PR/SD by irRC. Results: Among the 411 pts enrolled across the 3 MEL cohorts, 192 were on MK-3475 for ≥28 wk as of the analysis cut-off of 10/18/2013. Tumor flare was seen in 7 (3.6%) pts. In these pts, best overall response per irRC was CR (n = 1), PR (n = 4), and SD (n = 2). Atypical delayed response was seen in 6 (3.1%) pts. The 51 pts with PD by RECIST but CR/PR/SD by irRC had favorable OS compared with the 145 pts with PD by both criteria (Table). Conclusions: MEL pts treated with MK-3475 may experience unique patterns of response and should be managed accordingly. Similar to what has been observed with ipilimumab, conventional criteria such as RECIST may underestimate the benefit of MK-3475 in approximately 10% of treated pts. An updated version of response criteria that incorporate new data on PD-1 inhibitors may be appropriate for future consideration. Clinical trial information: NCT01295827. OS Rate 3 mo 6 mo 12 mo Pts with CR/PR/SD by RECIST and irRC (n = 215) 100% 98% 92% Pts with PD by RECIST but CR/PR/SD by irRC (n = 51) 100% 94% 67% Pts with PD by RECIST and irRC (n = 145) 79% 53% 34%
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.019 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".