JCO precision oncology · 2026
Olaparib in Patients With Solid Tumors With ATM Alterations: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.
СтатьяКлиническое исследование II фазыНазвание и аннотация: Перевод в очереди
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Carrizosa Daniel R, Rothe Michael, Mangat Pam K, Garrett-Mayer Elizabeth, Behl Deepti, Adesunloye Bamidele, Pisick Evan, Beekman Kathleen W, Dotan Efrat, Akce Mehmet, Alese Olatunji B, Sahai Vaibhav, Klute Kelsey A, Aragon-Ching Jeanny B, Cooper Kathrine A, Thota Ramya, Meric-Bernstam Funda, Hosein Peter J, Maestas Erika C, Moyers Justin T, Powell Steven, Zhao Song, Hobbs Evthokia, Rueter Jens, Sohal Davendra P S, Taylor Mark A, Hinshaw Dominique C, Gregory Abigail, Grantham Gina N, Halabi Susan, Schilsky Richard L
Аннотация
PURPOSE: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of targeted agents in patients with advanced cancer and genomic alterations. Results of four cohorts of patients with ATM-altered tumors treated with olaparib are reported: colorectal cancer (CRC), lung cancer (LC), pancreatic cancer (PC), and other solid tumors (histology-pooled, HP).
METHODS: Eligible patients had advanced solid tumors, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16 weeks duration. For histology-specific cohorts, Simon's two-stage design was based on a null DC rate of 15% versus 35% (power = 0.85; α = .10). For the HP cohort, the hypothesized null DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points were OR, progression-free survival, overall survival, duration of response or SD, and safety.
RESULTS: Patients with CRC (n = 30), LC (n = 20), PC (n = 28), or other advanced cancers (n = 38) with ATM alterations were enrolled. The DC rates were 23% (one-sided 90% CI, 8 to 100; P = .38), 45% (one-sided 90% CI, 32 to 100; P = .0004), 28% (one-sided 90% CI, 14 to 100; P = .14), and 25% (one-sided 90% CI, 16 to 100), respectively. The null hypothesized 15% DC rate was rejected for the LC and HP cohorts but not the CRC and PC cohorts. Twenty of 116 patients (17%) experienced treatment-related grade 3 adverse events (AE) or serious AEs.
CONCLUSION: Olaparib met the prespecified criteria to declare a signal of activity in patients with ATM-altered cancer within the LC and HP cohorts but not the CRC or PC cohorts.
METHODS: Eligible patients had advanced solid tumors, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16 weeks duration. For histology-specific cohorts, Simon's two-stage design was based on a null DC rate of 15% versus 35% (power = 0.85; α = .10). For the HP cohort, the hypothesized null DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points were OR, progression-free survival, overall survival, duration of response or SD, and safety.
RESULTS: Patients with CRC (n = 30), LC (n = 20), PC (n = 28), or other advanced cancers (n = 38) with ATM alterations were enrolled. The DC rates were 23% (one-sided 90% CI, 8 to 100; P = .38), 45% (one-sided 90% CI, 32 to 100; P = .0004), 28% (one-sided 90% CI, 14 to 100; P = .14), and 25% (one-sided 90% CI, 16 to 100), respectively. The null hypothesized 15% DC rate was rejected for the LC and HP cohorts but not the CRC and PC cohorts. Twenty of 116 patients (17%) experienced treatment-related grade 3 adverse events (AE) or serious AEs.
CONCLUSION: Olaparib met the prespecified criteria to declare a signal of activity in patients with ATM-altered cancer within the LC and HP cohorts but not the CRC or PC cohorts.