Open-label phase II/III study of nivolumab plus standard of care versus standard of care for first-line treatment of metastatic colorectal cancer: Checkmate-9X8.
Bibliographic record
Abstract
TPS718 Background: 5-FU-containing regimens with oxaliplatin or irinotecan and a biologic agent such as the VEGF inhibitor bevacizumab (BEV) are standard-of-care (SOC) options for the treatment of first-line (1L) metastatic colorectal cancer (mCRC). However, the objective response rate (ORR) with these regimens is 38%, and median progression-free survival (PFS) and median overall survival (OS) are 9.4 months and 21.3 months, respectively (Saltz et al. JCO 2007). Thus, there is a need for therapies that will provide durable clinical responses and improved survival. mCRC tumors represent classic “cold” tumors characterized by low expression of inflammatory and immune signatures. Emerging evidence suggests that there may be subtypes of mCRC that could benefit from synergistic immunogenic stimuli with immunotherapy agents combined with other compounds. The immune checkpoint inhibitor nivolumab (NIVO) enhances antitumor T-cell activity through the inhibition of the programmed death-1 receptor. Chemotherapy and BEV may have potential synergistic immune-stimulatory effect on the tumor and its microenvironment. Therefore, combining NIVO with SOC may enhance the antitumor immune response and improve clinical activity in 1L mCRC. The international, multicenter, open-label phase 2/3 CheckMate-9X8 (NCT03414983) trial will evaluate efficacy and safety of the combination of NIVO+SOC, compared with SOC alone, in previously untreated patients with mCRC. Methods: An estimated 180 patients aged ≥ 18 years with histologically confirmed mCRC, no prior therapy for mCRC, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and an adequate tissue sample, will be randomized to receive either NIVO+SOC or SOC alone. Patients who have had prior treatment with a checkpoint inhibitor; have autoimmune, cardiovascular, or hepatic disease; or test positive for hepatitis B or C (indicating detectable virus) will be excluded. The primary endpoint is PFS assessed by blinded independent central review (BICR) using RECIST v1.1. Secondary endpoints include ORR, disease control rate, duration of response, and time to response, all by BICR; OS; and safety. Clinical trial information: NCT03414983.
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 | 0.002 |
| Bibliometrics | 0.001 | 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 | 0.004 |
| Insufficient payload (model declined to judge) | 0.008 | 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".