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| Ref Type | Journal Article | ||||||||||||
| PMID | (38039429) | ||||||||||||
| Authors | Rohatgi N, Rothe M, Mangat PK, Garrett-Mayer E, Meric-Bernstam F, Pisick E, Alese OB, Reynolds CM, Thota R, Vaccaro GM, von Mehren M, Arend RC, Chiu VK, Duvivier HL, Gold PJ, Hack K, Marr AS, Winer A, Grantham GN, Hinshaw DC, Gregory A, Halabi S, Schilsky RL | ||||||||||||
| Title | Nivolumab Plus Ipilimumab in Patients With Solid Tumors With ATM Mutations: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study. | ||||||||||||
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| Abstract Text | 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.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.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.Nivolumab plus ipilimumab did not meet prespecified criteria to declare a signal of activity in patients with solid tumors with ATM mutations. | ||||||||||||
| Molecular Profile | Treatment Approach |
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| Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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| Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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| Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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| ATM inact mut | Advanced Solid Tumor | no benefit | Ipilimumab + Nivolumab | Phase II | Actionable | In a Phase II trial (TAPUR), Opdivo (nivolumab) and Yervoy (ipilimumab) combination treatment did not meet predetermined efficacy criteria in patients with advanced solid tumors harboring ATM mutations, resulting in an objective response rate of 14% (4/29, 1 complete and 3 partial responses), a disease control rate of 24% (7/29), with stable disease of at least 16 weeks in 3 patients, a median progression-free survival of 9 weeks, and median overall survival of 28 weeks (PMID: 38039429; NCT02693535). | 38039429 |