Trial results for a Phase 2 study investigating Nivolumab and Sorafenib in participants with unresectable, locally advanced, or metastatic liver cancer were posted on ClinicalTrials.gov on 2025-02-11. The study determined the maximum tolerated dose (MTD) of sorafenib to be 400 milligrams (mg) once per day and reported high proportions of participants experiencing treatment-related adverse events.
Background
Liver cancer that cannot be surgically removed, or has spread, presents significant treatment challenges. Sorafenib is a kinase inhibitor that may inhibit cancer cell growth by blocking enzymes needed for cell growth. Nivolumab is an immunotherapy that works by helping the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Trial design
This completed Phase 2 trial (NCT03439891) enrolled 16 participants with Stage III, Stage IIIA, Stage IIIB, Stage IIIC, or Stage IV Hepatocellular Carcinoma. The study investigated the combination of nivolumab and sorafenib in patients with unresectable, locally advanced, or metastatic liver cancer.
Key results
The key results from the trial focused on safety and tolerability outcomes:
- The maximum tolerated dose (MTD) for sorafenib in Part 1 of the study was determined to be 400 milligrams (mg) once per day.
- In Part 2 (Child Pugh B Expansion Cohort), the proportion of participants experiencing Grade 3 or higher treatment-related adverse events was 0.6 proportion of participants.
- The proportion of participants with any treatment-related adverse events was 1.00 proportion of participants across the starting dose schedule, escalated dose schedule, and the Child Pugh B expansion cohort.
- Across all treatment groups combined, the proportion of participants reporting immune-related adverse events (irAE) was 0.94 proportion of participants. For Child-Pugh B participants specifically, this proportion was 0.83 proportion of participants.
- Dose delays due to toxicity were observed in 0.833 proportion of participants in the starting dose schedule, 1.00 proportion of participants in the escalated dose schedule, and 0.8 proportion of participants in the Child Pugh B expansion cohort.
- Dose reductions due to toxicity occurred in 0.33 proportion of participants in the starting dose schedule and 0.2 proportion of participants in the escalated dose schedule.
What this means
The findings from this Phase 2 trial provide important safety and tolerability data for the combination of nivolumab and sorafenib in patients with advanced liver cancer. The establishment of 400 mg once per day as the maximum tolerated dose for sorafenib, alongside the high rates of treatment-related adverse events, immune-related adverse events, dose delays, and dose reductions, indicates that this combination therapy has a significant toxicity profile. These results are crucial for informing future studies and clinical decisions regarding the management of advanced hepatocellular carcinoma with this drug combination, particularly concerning patient selection and supportive care strategies.
Source
The information for this article was sourced from ClinicalTrials.gov, a public database of clinical studies. The trial results for study NCT03439891, titled 'Sorafenib and Nivolumab in Treating Participants With Unresectable, Locally Advanced or Metastatic Liver Cancer,' were posted on 2025-02-11 on clinicaltrials.gov.