Trial results for the Phase 1/2 study (NCT03024437) investigating atezolizumab in combination with entinostat and bevacizumab for patients with advanced renal cell carcinoma were posted on ClinicalTrials.gov on 2025-03-20. The trial, which was terminated, reported objective response rates of 62.5% in Phase II Cohort A and 33.3% in Phase II Cohort B, along with median overall survival of 51.6 months and 31.2 months, respectively.
Background
The study investigated atezolizumab, a PD-L1 inhibitor, in combination with entinostat and bevacizumab for the treatment of patients with advanced renal cell carcinoma and metastatic cancer. The hypothesis explored was that entinostat, a histone deacetylase (HDAC) inhibitor, could enhance the anti-tumor effect of PD-L1 inhibition by suppressing Treg function.
Trial design
The study (NCT03024437) was a Phase 1/2 trial that enrolled 31 participants with metastatic cancer and renal cancer. The interventions included atezolizumab, bevacizumab, and entinostat. The Phase 1 portion aimed to determine the recommended Phase 2 dose of entinostat. The Phase 2 portion assessed objective response, progression-free survival, and overall survival. The trial was ultimately terminated.
Key results
The trial results provided data for both Phase 1 and Phase 2 objectives.
- For Phase 1, the recommended Phase 2 dose of entinostat was determined to be 5 mg.
Objective response rates for Phase 1 dose levels were:
- Phase I - Dose Level 1: 50% (95% Confidence Interval)
- Phase I - Dose Level 2: 20% (95% Confidence Interval)
- Phase I - Dose Level 3: 83.3% (95% Confidence Interval)
For Phase 2, key efficacy outcomes were reported for two cohorts:
- Phase II - Cohort A:
- Percentage of Patients With Objective Response: 62.5% (95% Confidence Interval)
- Median Progression-free Survival: 13.7 months (95% Confidence Interval)
- Median Overall Survival: 51.6 months (95% Confidence Interval)
- Phase II - Cohort B:
- Percentage of Patients With Objective Response: 33.3% (95% Confidence Interval)
- Median Progression-free Survival: 9.8 months (95% Confidence Interval)
- Median Overall Survival: 31.2 months (95% Confidence Interval)
What this means
The posted results from this Phase 1/2 trial provide insights into the combination of atezolizumab, entinostat, and bevacizumab for advanced renal cell carcinoma. The identification of a recommended Phase 2 dose for entinostat and the observed objective response rates, progression-free survival, and overall survival data across the Phase 2 cohorts offer preliminary efficacy signals. The termination of the trial suggests that further development in this specific combination and indication might not be pursued, or that the study did not meet its objectives for continuation, though the reasons for termination are not detailed in the results data.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03024437, titled "Atezolizumab in Combination With Entinostat and Bevacizumab in Patients With Advanced Renal Cell Carcinoma," were posted on 2025-03-20 on clinicaltrials.gov.