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Pembrolizumab in Patients With Tumors With High Tumor Mutational Burden: Results From the Targeted Agent and
Herbert L Duvivier1, Michael Rothe2, Pam K Mangat2
1Cancer Treatment Centers of America-Atlanta, Part of City of Hope, Newnan, GA.
Purpose:
The Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a pragmatic basket trial evaluating antitumor activity of approved targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from cohorts of patients with high tumor mutational burden (HTMB, defined as ≥9 mutations per megabase) with advanced colorectal cancer (CRC) and other advanced cancers treated with pembrolizumab are reported.
Methods:
Eligible patients were 18 years and older with measurable tumors and a lack of standard treatment options, an Eastern Cooperative Oncology Group performance status of 0-1, and adequate organ function. The primary end point was disease control (DC), defined as complete or partial response or stable disease (SD) of at least 16-weeks duration. For the CRC cohort, Simon's two-stage design with a null DC rate of 15% versus 35% (power = 0.85; α = .10) was used. Low accruing histology-specific cohorts were collapsed into one histology-pooled (HP) cohort. For the HP cohort, the null hypothesis of a DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points included objective response (OR), safety, progression-free survival, overall survival, duration of response, and duration of SD.
Results:
Seventy-seven patients with HTMB with CRC (n = 28) or advanced cancers (n = 49) were treated with pembrolizumab. For the CRC cohort, the DC rate was 31% (P = .04) and the OR rate was 11%. For the HP cohort, the DC rate was 45% (one-sided 90% CI, 35 to 100) and the OR rate was 26%. The null hypothesis of a 15% DC rate was rejected for both cohorts. Twelve of 77 patients experienced treatment-related grade 3 adverse events (AEs) or serious AEs, including two deaths.
Conclusion:
Pembrolizumab demonstrated antitumor activity in pretreated patients with advanced cancers and HTMB.
Insights
Pembrolizumab showed antitumor effects in advanced cancer patients with high tumor mutational burden (HTMB). This study in the Targeted Agent and Profiling Utilization Registry (TAPUR) trial found disease control in both colorectal and other advanced cancer cohorts.
Area of Science:
- Oncology
- Genomics
- Clinical Trials
Background:
- The Targeted Agent and Profiling Utilization Registry (TAPUR) study is a pragmatic basket trial.
- It evaluates the antitumor activity of approved targeted agents in patients with advanced cancers and actionable genomic alterations.
Purpose of the Study:
- To report data from cohorts of patients with high tumor mutational burden (HTMB) and advanced colorectal cancer (CRC) or other advanced cancers treated with pembrolizumab.
- To assess the antitumor activity of pembrolizumab in these patient populations.
Main Methods:
- Patients with advanced cancers, measurable tumors, and no standard treatment options were enrolled.
- The primary endpoint was disease control (DC) of at least 16 weeks. Simon's two-stage design was used for the CRC cohort.
- Low-accruing histology-specific cohorts were combined into a histology-pooled (HP) cohort for analysis.
Main Results:
- Seventy-seven patients with HTMB (28 CRC, 49 other advanced cancers) received pembrolizumab.
- The DC rate was 31% in the CRC cohort and 45% in the HP cohort, rejecting the null hypothesis of 15% DC.
- Objective response rates were 11% for CRC and 26% for HP. Grade 3 or serious adverse events occurred in 12 patients.
Conclusions:
- Pembrolizumab demonstrated antitumor activity in pretreated patients with advanced cancers and high tumor mutational burden.
- The findings support the use of pembrolizumab in specific advanced cancer patient populations with HTMB.
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