Nivolumab (NIVO) + 5-fluorouracil/leucovorin/oxaliplatin (mFOLFOX6)/bevacizumab (BEV) versus mFOLFOX6/BEV for first-line (1L) treatment of metastatic colorectal cancer (mCRC): Phase 2 results from CheckMate 9X8.
Bibliographic record
Abstract
8 Background: Standard 1L therapies for mCRC include a fluoropyrimidine with oxaliplatin and/or irinotecan, and a biologic agent. NIVO may enhance antitumor activity in combination with 1L standard therapies within a subset of patients (pts) with mCRC. CheckMate 9X8 evaluated NIVO + mFOLFOX6/BEV vs mFOLFOX6/BEV in 1L mCRC (NCT03414983). Methods: Adults with previously untreated, unresectable, mCRC were randomized 2:1 to NIVO 240 mg + mFOLFOX6/BEV Q2W (NIVO + standard-of-care [SOC]) or mFOLFOX6/BEV Q2W (SOC). Primary endpoint was progression-free survival (PFS) assessed by blinded independent central review (BICR) per RECIST v1.1. Key secondary endpoints included objective response rate (ORR), disease control rate (DCR), time to response (TTR), duration of response (DOR), overall survival (OS), and safety. Results: 195 pts were randomized to NIVO + SOC (n = 127) or SOC (n = 68). Median (range) follow-up was 23.7 (0–33.2) months (mo; NIVO + SOC) vs 23.2 (0–32.3) mo (SOC). Median (range) duration of therapy was 9.9 (0.1–31.8+) mo (NIVO + SOC) and 7.7 (0.1–26.7+) mo (SOC). The HR (95% CI) for PFS was 0.81 (0.53–1.23; P = 0.30), which did not meet the prespecified threshold for statistical significance (median PFS, 11.9 mo in both arms; Table). PFS rates after 12 mo were higher with NIVO + SOC vs SOC (Table). ORR was 60% (NIVO + SOC) and 46% (SOC; odds ratio 1.72 [95% CI 0.96–3.10]) and median (95% CI) DOR was 12.9 (9.0–13.1) mo (NIVO + SOC) and 9.3 (7.5–11.3) mo (SOC; Table). Rates of grade 3−4 treatment-related adverse events (TRAEs) were higher with NIVO + SOC; however, no new safety signals were identified (Table). Biomarker analyses, including tumor mutational burden and baseline CD8 levels, will be presented. Conclusions: The primary endpoint of PFS was not met; however, NIVO + SOC showed higher PFS rates after 12 mo, a higher response rate, and more durable responses compared with SOC, along with acceptable safety, in 1L mCRC. Clinical trial information: NCT03414983. [Table: see text]
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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 | 0.001 | 0.001 |
| 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 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".