A phase II, randomized study of nivolumab (NIVO), NIVO plus linrodostat mesylate, or NIVO plus intravesical bacillus Calmette-Guerin (BCG) in BCG-unresponsive, high-risk, nonmuscle invasive bladder cancer (NMIBC): CheckMate 9UT.
Bibliographic record
Abstract
TPS5090 Background: Immune checkpoint inhibitors, including NIVO (anti–PD-1), have demonstrated favorable tolerability and efficacy profiles, ushering in a new treatment (tx) paradigm for advanced bladder cancer (advBC). However, an unmet need exists for new effective tx options in earlier stages of disease, specifically for patients (pts) with BCG-unresponsive, high-risk NMIBC. Increased IDO and PD-L1 expression in NMIBC tumors (Inman, et al. Cancer 2007; Hudolin, et al. Anticancer Res 2017), support the combination of anti–PD-1 and IDO1 inhibition in NMIBC. Linrodostat mesylate, a selective, potent, once-daily IDO1 inhibitor, has demonstrated clinical activity in combination with NIVO in pts with immunotherapy-naive advBC who received ≥ 1 prior line of therapy (objective response rate, 37%; Tabernero, et al. J Clin Oncol 2018;36(suppl) [abstr 4512]). Furthermore, high levels of PD-L1 expression have been reported in patients not responding to BCG tx. These findings provide a rationale for investigation of NIVO ± linrodostat ± intravesical BCG therapy in BCG-unresponsive high-risk NMIBC. Here we describe a phase 2, randomized, open-label study assessing the safety and efficacy of NIVO ± linrodostat ± intravesical BCG in pts with BCG-unresponsive, high-risk NMIBC (NCT03519256). Methods: Pts aged ≥ 18 years with BCG-unresponsive (per February 2018 FDA guidance), high-risk NMIBC, defined as carcinoma-in-situ (CIS) with or without papillary component, any T1, or Ta high-grade lesions, will be enrolled. Pts must have urothelial carcinoma as the predominant histological component ( > 50%). Key exclusion criteria include locally advanced or metastatic BC, upper urinary tract disease within 2 years, prostatic urethral disease within 1 year, and prior immunotherapy. Using a novel adaptive-type design, pts will be randomized to 1 of 4 tx arms with NIVO ± linrodostat ± BCG. Primary endpoints include proportion of pts with CIS with complete response (CR) and duration of CR in pts with CIS. Secondary endpoints are progression-free survival and safety. This global study in 14 countries is underway, with a target enrollment of 436 pts. Clinical trial information: NCT03519256 .
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 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 | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 0.002 |
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".