# CAVE mCRC

Source: https://onco.cc/trials/cave/  
OnCo record `cave` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Adding a PD-L1 antibody to an EGFR antibody given a second time helped most in patients whose blood showed no resistance mutations, a seven-month difference in survival between the two groups.

## Summary

CAVE enrolled 77 patients with pretreated RAS wild-type metastatic colorectal cancer, 71 of them microsatellite-stable, and gave cetuximab rechallenge with avelumab. The trial met its primary endpoint with a median overall survival of 11.6 months (95% CI 8.4 to 14.8) and median progression-free survival of 3.6 months. Baseline circulating tumour DNA for KRAS, NRAS, BRAF and EGFR S492R was analysable in 67 of 77 (87 percent); 48 patients were wild-type in plasma and 19 mutated. Median overall survival was 17.3 months in the plasma wild-type group against 10.4 months in the mutated group (hazard ratio 0.49, 95% CI 0.27 to 0.90, p=0.02), and progression-free survival 4.1 against 3.0 months (hazard ratio 0.42, 0.23 to 0.75, p=0.004). Grade 3 cutaneous eruption affected 14 percent. A later pooled analysis of 180 patients found that the absence of liver metastases and a longer anti-EGFR-free interval mark out who benefits. Like CHRONOS, CAVE is single-arm: it establishes that plasma RAS status selects for rechallenge benefit, not that rechallenge beats standard later-line treatment.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-24
- Also known as: CAVE
- Registry id: NCT04561336
- Phase: 2
- Setting: Pretreated RAS wild-type metastatic colorectal cancer: cetuximab rechallenge with the PD-L1 antibody avelumab, single arm
- Sponsor: University of Campania Luigi Vanvitelli
- Enrolled: 77
- Result: Median overall survival 11.6 months overall; 17.3 months with RAS and BRAF wild-type plasma against 10.4 months with mutated plasma (hazard ratio 0.49).
- Outcomes: Overall survival: Cetuximab rechallenge plus avelumab 11.6 months; Overall survival by baseline plasma RAS and BRAF status: Plasma wild-type 17.3 months vs Plasma mutated 10.4 months, HR 0.49
- Replication: A 2026 pooled analysis of 180 patients found median overall survival 15.7 months with cetuximab and avelumab against 12.9 months with cetuximab alone, with liver involvement and a short anti-EGFR-free interval marking out non-responders.

## Sources

- ClinicalTrials.gov NCT04561336: https://clinicaltrials.gov/study/NCT04561336
- CAVE: cetuximab plus avelumab as rechallenge therapy in RAS wild-type metastatic colorectal cancer (JAMA Oncology 2021): https://doi.org/10.1001/jamaoncol.2021.2915
- CAVE pooled analysis of clinical factors and outcomes (ESMO Gastrointestinal Oncology 2026): https://doi.org/10.1016/j.esmogo.2026.100398

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [Monoclonal antibodies](https://onco.cc/technologies/monoclonal-antibody/)
- targets: [EGFR](https://onco.cc/targets/egfr/), [PD-1](https://onco.cc/targets/pd1/)
- drugs: [Avelumab](https://onco.cc/drugs/avelumab/), [Cetuximab](https://onco.cc/drugs/cetuximab/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)](https://onco.cc/terms/msi/)
- trials: [CHRONOS](https://onco.cc/trials/chronos/)

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