BMS-986205, an indoleamine 2, 3-dioxygenase 1 inhibitor (IDO1i), in combination with nivolumab (nivo): Updated safety across all tumor cohorts and efficacy in advanced bladder cancer (advBC).
Bibliographic record
Abstract
358 Background: Nivo (antiPD-1) has shown durable responses and manageable safety (ORR, 19.6%; grade 3‒4 treatment-related AEs [TRAEs], 18%) in advBC (Sharma et al. Lancet Oncol 2017), but prolonging survival in more pts requires additional approaches to overcome tumor evasion mechanisms. IDO1 allows tumor escape through kynurenine (KYN) production, which stimulates regulatory T cells and suppresses effector T-cell proliferation. Anti─PD-1 can upregulate IDO1, supporting the rationale for combining nivo with an IDO1i. BMS-986205 is a selective, potent, once-daily (QD) oral IDO1i that works early in the IDO1 pathway to reduce KYN production. BMS-986205 + nivo showed favorable safety and efficacy in heavily pretreated pts with select solid tumors (Luke et al. SITC 2017; NCT02658890). Updated safety across all tumor cohorts and efficacy in the immuno-oncology (I-O)naive advBC cohort are reported. Methods: Dose-escalation methods in this phase 1/2a, open-label study were previously described; during expansion, pts received BMS-986205 100 or 200 mg QD + nivo 240 mg IV Q2W or 480 mg IV Q4W. Objectives included safety and ORR by RECIST v1.1 (includes unconfirmed responses). Results: As of Mar 2018, 516 pts received BMS-986205 + nivo; 45% had ≥2 prior regimens. TRAEs occurred in 57% of pts (grade 3‒4, 12%), the most common being fatigue (15%) and nausea (12%); 19 pts (4%) discontinued due to TRAEs, and 3 pts ( < 1%) died due to a TRAE (myocarditis, Stevens-Johnson syndrome, and hepatic failure). In all treated pts and within the advBC cohort (n = 30), the frequency and severity of TRAEs and rate of discontinuation due to TRAEs was lower with the 100- vs 200-mg BMS-986205 dose. Among the 27 pts with I-Onaive advBC, with a median duration of follow-up of 24 wk, ORR was 37% (3 CRs, 7 PRs), and the DCR was 56%; ORR in pts with tumor PD-L1 ≥1% (Dako PD-L1 IHC 28-8 pharmDx assay; n = 14) vs < 1% (n = 10) was 50% vs 30%. Conclusions: BMS-986205 + nivo was well tolerated in heavily pretreated pts, and tolerability was improved with the 100-mg BMS-986205 dose. Preliminary evidence of efficacy was observed in advBC, supporting further evaluation of BMS-986205 + nivo. Clinical trial information: NCT02658890.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".