Preliminary results of a phase II study of neoadjuvant checkpoint blockade for surgically resectable undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated liposarcoma (DDLPS).
Bibliographic record
Abstract
11505 Background: is a randomized, phase II non-comparative trial evaluating the efficacy of neoadjuvant checkpoint blockade [nivolumab (N) or ipilimumab/ nivolumab (I/N)] in patients (pts) with surgically resectable retroperitoneal DDLPS or extremity/truncal UPS treated with concurrent neoadjuvant radiation therapy (RT, UPS only). Methods: Primary endpoint was pathologic (path) response. Secondary endpoints were safety, RECIST response, recurrence-free survival, overall survival and patient-reported outcomes. Biospecimens (tumor, blood, fecal microbiome) at baseline, on therapy, and at time of surgery were collected and will be assessed for immune-based prognostic biomarkers. We assessed correlation between radiographic and pathologic response by linear regression. Correlative analyses includes assessment of tumor PD-L1 expression, characterization of tumor immune infiltrates by multiplex immunohistochemistry, and transcriptomic and genomic analyses. Results: Of the 25 pts enrolled; 24 are evaluable for response (14 DDLPS, 9 UPS). Clinical activity was variable by histologic subtype and treatment with RT. Median path response in the UPS cohort was 95% [95% CI 85–99] and was similar between the N/RT and I/N/RT groups (Table). Median path response in the DDLPS cohort was 22.5% [95% CI 85–99; Table]. Median change in tumor size (radiographic response) was -4% and +9% in the UPS and DDLPS cohorts, respectively. There was no correlation between path response and radiographic response (R2 0.0309; p = 0.43). Of 8 pts with path response ≥ 85%, there was 1 partial response, 5 stable disease and 2 progressive disease by RECIST criteria. There was 1 delay to surgery due to grade 3 hyperbilirubinemia (Arm B). There was no difference in toxicity between N/RT and I/N/RT. Conclusions: N/RT and I/N/RT have significant clinical activity in UPS; more than expected compared to historic controls. Toxicity profiles were as expected and the majority of patients underwent resection without delay. Larger studies evaluating N/RT in UPS are warranted given the significant path response in this cohort. RECIST was not associated with path response and better markers of on-treatment clinical activity are needed. Correlative analyses that may guide combination strategies are ongoing and will be presented at the meeting. Clinical trial information: NCT03307616 .
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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 | 0.002 |
| 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 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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 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".