Pembrolizumab

The FDA approved pembrolizumab for the treatment of metastatic solid tumors with a TMB of at least 10 Mut/Mb, based on the KEYNOTE-158 trial.[90]

The FDA approved pembrolizumab for the treatment of metastatic solid tumors with a TMB of at least 10 Mut/Mb, based on the KEYNOTE-158 trial.[90]

KEYNOTE-158 (NCT02628067) was a multicohort, open-label, nonrandomized, phase II multinational study. Patients had metastatic solid malignancies, treated with at least one previous line of therapy. Participants received pembrolizumab 200 mg intravenously every 3 weeks for up to 35 cycles. TMB was assessed in formalin-fixed paraffin-embedded tumor samples using the FoundationOne CDx assay. A total of 105 of 805 evaluable patients had high TMB (≥10 Mut/Mb).

The FDA approved pembrolizumab for the treatment of metastatic solid tumors with a TMB of at least 10 Mut/Mb, based on the KEYNOTE-158 trial.[90]

The primary outcome was objective response rate. Objective responses were observed in 30 of 102 patients (29%) in the TMB-high group and 43 of 688 patients (6%) in the non-TMB-high group. Grade 3 to 5 treatment-related adverse events occurred in 16 patients. One patient died of pneumonia that was assessed by the investigator to be treatment related.

The TAPUR study (NCT02693535) was a phase II basket trial done to identify the efficacy of commercially available targeted agents in patients with advanced cancers and genomic alterations known to be drug targets. TAPUR results from patients with metastatic breast cancer and high TMB have been reported. The primary end point was disease control (objective response or stable disease for ≥16 weeks).[91][Level of evidence C3]

The TAPUR study (NCT02693535) was a phase II basket trial done to identify the efficacy of commercially available targeted agents in patients with advanced cancers and genomic alterations known to be drug targets. TAPUR results from patients with metastatic breast cancer and high TMB have been reported. The primary end point was disease control (objective response or stable disease for ≥16 weeks).[91][Level of evidence C3]

The study enrolled 28 patients with metastatic breast cancer and high TMB. TMB ranged from 9 to 37 Mut/Mb.

The TAPUR study (NCT02693535) was a phase II basket trial done to identify the efficacy of commercially available targeted agents in patients with advanced cancers and genomic alterations known to be drug targets. TAPUR results from patients with metastatic breast cancer and high TMB have been reported. The primary end point was disease control (objective response or stable disease for ≥16 weeks).[91][Level of evidence C3]

Disease control was noted in 37% of patients, with objective response noted in 21% of patients.

The TAPUR study (NCT02693535) was a phase II basket trial done to identify the efficacy of commercially available targeted agents in patients with advanced cancers and genomic alterations known to be drug targets. TAPUR results from patients with metastatic breast cancer and high TMB have been reported. The primary end point was disease control (objective response or stable disease for ≥16 weeks).[91][Level of evidence C3]

The median PFS was 10.6 weeks and the median OS was 30.6 weeks.