Sequential immunotherapy in rare variant renal cell carcinomafinal report of UNISoN (ANZUP 1602): Nivolumab then ipilimumab + nivolumab in advanced nonclear cell renal cell carcinoma.
Bibliographic record
Abstract
4537 Background: Immune checkpoint immunotherapy (ICI) is active against many cancers. Many people are failed by PD1 inhibition alone, but not all patients benefit, nor require combination ICI treatment. UNISoN (NCT03177239) previously reported outcomes in people with non-clear cell renal cell carcinoma (nccRCC) receiving nivolumab (N) monotherapy, and N plus ipilimumab (I) in those whose cancers progressed after N alone. We present the final planned report. Methods: Population, Intervention, Analysis: Participants (pts) with advanced nccRCC with good performance status (ECOG 0/1) received N 240mg q2w alone (Part 1). Those with cancers refractory to N at 3 months were offered combination I (1mg/kg) + N (3mg/kg) q3w for up to 4 doses, followed by N 240mg q2w for a maximum total of 12 months of N (Part 2). UNISoN was powered to identify a clinically-relevant objective tumor response rate (OTRR) of 30% (assuming 15% was not relevant) among people receiving I+N in Part 2. Results: 85 pts with a representative spectrum of nccRCC histologies were enrolled and received N. Amongst the total population enrolled to UNISoN Part 1/2, mOS was 24 (16-28) months and 12m OS was 65% (54%-74%); of those proceeding to Part 2, the mOS was 10 (6-17) months only. Overall, 17% (10%-27%; 14/83) and 10% (3%-23%; 4/41) of pts experienced a response from N alone or I+N, respectively. 41 pts refractory to N received I+N. Overall in Part 2, the median time on treatment was 2.1 (95% CI 1.8, 2.8) months, the median number of cycles was 3; median follow-up at final analysis was 22 (16-30) months. In this population, the median PFS was 2.6 (2.2-3.8) months and 12m PFS was 11% (4%-23%). 13% (7%-22%) of patients were free of progression or death at 24 months. The primary endpoint was not met; only 80% of pts failed by N were assessable for response in Part 2. Overall tumor responses from N alone or I+N were more common in pts with papillary histology; pts with chromophobe histology had poor outcomes. No late toxicity safety signals were observed. Conclusions: Some pts with nccRCC benefit from N alone, or addition of I when disease is inadequately controlled by N alone, however most pts have limited benefit from ICI. More effective therapeutic options are needed for the majority of people with rare variant renal cell carcinomas. Novel markers of response are required to more rapidly predict pts who will progress on N. Translational research to identify predictive biomarkers of response is ongoing. Clinical trial information: NCT03177239.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".