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Nivolumab Plus Ipilimumab in Patients With Solid Tumors With ATM Mutations: Results From the Targeted Agent and
Nitin Rohatgi1, Michael Rothe2, Pam K Mangat2
1Sutter Medical Center, Sacramento, CA.
Purpose:
The Targeted Agent and Profiling Utilization Registry Study is a phase II basket study evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancers with genomic alterations known to be drug targets. Results of a cohort of patients with solid tumors with ATM mutations treated with nivolumab plus ipilimumab are reported.
Methods:
Eligible patients had measurable disease (RECIST v.1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. Primary end point was disease control (DC), defined as complete (CR) or partial (PR) response or stable disease (SD) of at least 16 weeks duration (SD16+). Low-accruing histology-specific cohorts with ATM mutations treated with nivolumab plus ipilimumab were collapsed into a single histology-pooled cohort for this analysis. The results were evaluated based on a one-sided exact binomial test with a null DC rate of 15% versus 35% (power = .84; α = .10). Secondary end points were objective response (OR), progression-free survival, overall survival, duration of response, duration of SD, and safety.
Results:
Twenty-nine patients with 10 tumor types with ATM mutations were enrolled from January 2018 to May 2020. One patient was not evaluable for efficacy. One CR, three PR, and three SD16+ were observed for DC and OR rates of 24% (P = .13; one-sided 90% CI: 14 to 100) and 14% (95% CI: 4 to 32), respectively. The null hypothesis of 15% DC rate was not rejected. Eleven patients had one treatment-related grade 3 adverse event (AE) or serious AE. There were two treatment-related patient deaths including immune-related encephalitis and respiratory failure.
Conclusion:
Nivolumab plus ipilimumab did not meet prespecified criteria to declare a signal of activity in patients with solid tumors with ATM mutations.
Insights
This study found that nivolumab plus ipilimumab did not show significant antitumor activity in patients with advanced solid tumors harboring ATM mutations. Further research is needed to explore targeted therapies for these specific genomic alterations.
Area of Science:
- Oncology
- Genomics
- Clinical Trials
Background:
- The Targeted Agent and Profiling Utilization Registry (TAPUR) study investigates targeted agents in advanced cancers with known genomic alterations.
- This analysis focuses on a cohort of patients with solid tumors and ATM mutations treated with nivolumab plus ipilimumab.
Purpose of the Study:
- To evaluate the antitumor activity of nivolumab plus ipilimumab in patients with advanced solid tumors characterized by ATM mutations.
- To determine if the combination therapy meets predefined criteria for disease control.
Main Methods:
- A phase II basket study design was employed, enrolling patients with measurable disease and ECOG performance status 0-2.
- Disease control (complete response, partial response, or stable disease for ≥16 weeks) was the primary endpoint, assessed using a one-sided exact binomial test.
- Low-accruing histology-specific cohorts were pooled for analysis, with safety and other efficacy endpoints also monitored.
Main Results:
- Twenty-nine patients with ATM-mutated solid tumors were enrolled; one was not evaluable for efficacy.
- The observed disease control rate was 24% (90% CI: 14% to 100%), and the objective response rate was 14% (95% CI: 4% to 32%).
- The combination did not meet the prespecified threshold to reject the null hypothesis of a 15% disease control rate. Grade 3 adverse events and two treatment-related deaths were reported.
Conclusions:
- Nivolumab plus ipilimumab did not demonstrate sufficient antitumor activity to warrant further investigation in patients with ATM-mutated solid tumors based on the study's criteria.
- The findings suggest that this specific combination therapy may not be effective for this patient population.
