Nivolumab (anti-PD-1; BMS-936558, ONO-4538) in combination with sunitinib or pazopanib in patients (pts) with metastatic renal cell carcinoma (mRCC).
Bibliographic record
Abstract
5010 Background: Antiangiogenic agents sunitinib (S) and pazopanib (P) are SOC for mRCC, but new therapies are needed as pts advance through therapy with limited survival benefit. We report preliminary results of a phase I trial of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, in combination with S or P in pts with mRCC. Methods: mRCC patients (≥1 prior systemic therapy) received nivolumab in combination with S (50 mg, 4 wks on, 2 wks off; arm S) or P (800 mg daily; arm P), until progression/unacceptable toxicity. Starting dose of nivolumab was 2 mg/kg IV Q3W (N2), with planned escalation to 5mg/kg IV Q3W (N5). Based on tolerability, arm S N5 cohort was expanded to treatment-naïve pts. Primary objectives were safety/tolerability and determination of maximum tolerated dose (MTD) for the combinations; secondary objective was antitumor activity (objective response rate [ORR] and duration of response [DOR]). Results: 7 pts were assigned to each of arms S N2 and N5. No dose-limiting toxicities (DLTs) were observed and MTD was not reached thus N5 was expanded with 19 additional pts (total n=33). Arm P enrolled 20 pts at N2; 4 DLTs (elevated ALT/AST [n=3], fatigue [n=1]) were observed, leading to closure of this arm. Grade 3–4 related AEs were observed in 24/33 pts (73%) in arm S and 12/20 pts (60%) in arm P. Most common related grade 3–4 AEs included elevated ALT (18%), hypertension and hyponatremia (15% each) in arm S and elevated ALT/ AST (20% each) and fatigue (15%) in arm P. Hepatotoxicities were manageable using treatment algorithms. Grade 3 pneumonitis occurred in 1 pt (arm S, N5). Grade 3–4 related AEs led to therapy discontinuation in 8/33 pts (24%; 1 N2, 7 N5) in arm S and 4/20 pts (20%) in arm P. ORR was 52% (17/33) in arm S and 45% (9/20) in arm P. Responses occurred by first assessment (6 wks) in 41% (arm S) and 56% (arm P) of responding pts and were durable (range: arm S: 12.1+ to 54 wks; arm P: 12.1 to 69.1+ wks). Stable disease rate was 33% (n=11) in arm S and 35% (n=7) in arm P. PFS rate at 24 wks was 78% for arm S and 55% for arm P. Conclusions: Nivolumab plus S or P showed encouraging antitumor activity and a manageable safety profile in pts with mRCC. Additional follow up will be presented. Clinical trial information: NCT01472081.
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 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 | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.000 | 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".