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PURPOSE The TAPUR Study is a phase II basket trial that aims to identify signals of antitumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known to be drug targets. Results in a cohort of patients with metastatic breast cancer (mBC) with high tumor mutational burden (HTMB) treated with pembrolizumab are reported. METHODS Patients with advanced mBC received standard doses of either 2 mg/kg or 200 mg infusions of pembrolizumab every 3 weeks. Simon's two-stage design was used with a primary study end point of disease control (DC) defined as objective response or stable disease of at least 16 weeks duration. If two or more patients in stage I achieved DC, the cohort would enroll 18 additional patients in stage II. Secondary end points include progression-free survival (PFS), overall survival, and safety. RESULTS Twenty-eight patients were enrolled from October 2016 to July 2018. All patients' tumors had HTMB ranging from 9 to 37 mutations/megabase. DC and objective response were noted in 37% (95% CI, 21 to 50) and 21% of patients (95% CI, 8 to 41), respectively. Median PFS was 10.6 weeks (95% CI, 7.7 to 21.1); median overall survival was 30.6 weeks (95% CI, 18.3 to 103.3). No relationship was observed between PFS and tumor mutational burden. Five patients experienced ≥ 1 serious adverse event or grade 3 adverse event at least possibly related to pembrolizumab consistent with the product label. CONCLUSION Pembrolizumab monotherapy has antitumor activity in heavily pretreated patients with mBC characterized by HTMB. Our findings support the recent US Food and Drug Administration approval of pembrolizumab for treatment of patients with unresectable or metastatic solid tumors with HTMB without alternative treatment options.

PURPOSE The Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a phase II pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancer with genomic alterations known to be drug targets. Results in a cohort of patients with non–small-cell lung cancer (NSCLC) with CDKN2A alterations treated with palbociclib are reported. METHODS Eligible patients were ≥ 18 years old with advanced NSCLC, no remaining standard treatment options, measurable disease, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function. Patients with NSCLC with CDKN2A alterations and no Rb mutations received palbociclib 125 mg orally once daily for 21 days, followed by 7 days off. Simon’s two-stage design was used with a primary study end point of objective response or stable disease (SD) of at least 16 weeks in duration. Secondary end points are progression-free survival (PFS), overall survival (OS), and safety. RESULTS Twenty-nine patients were enrolled from January 2017 to June 2018; two patients were not evaluable for response but were included in safety analyses. One patient with partial response and six patients with SD were observed, for a disease control rate of 31% (90% CI, 19% to 40%). Median PFS was 8.1 weeks (95% CI, 7.1 to 16.0 weeks), and median OS was 21.6 weeks (95% CI, 14.1 to 41.1 weeks). Eleven patients had at least 1 grade 3 or 4 adverse event (AE) or serious AE (SAE) possibly related to palbociclib (most common, cytopenias). Other AEs or SAEs possibly related to the treatment included anorexia, fatigue, febrile neutropenia, hypophosphatemia, sepsis, and vomiting. CONCLUSION Palbociclib monotherapy demonstrated evidence of modest antitumor activity in heavily pretreated patients with NSCLC with CDKN2A alterations. Additional investigation is necessary to confirm efficacy and utility of palbociclib in this population.

The Targeted Agent and Profiling Utilization Registry (TAPUR) Study identifies signals of antitumor activity of commercially available targeted agents in patients with advanced cancers that harbor genomic alterations known as drug targets. In this article, data from two cohorts of patients with pancreatic and biliary cancers withEligible patients age 12 years and older with advanced measurable or evaluable solid tumors are provided treatment according to protocol-specified genomic matching rules. The primary study end point is objective response or stable disease of at least 16 weeks duration. For each cohort, a Simon two-stage design was used with a futility evaluation after 10 patients. Secondary end points include safety, progression-free survival (PFS), and overall survival (OS).Between July 2016 and November 2017, 12 and 10 patients with pancreatic and biliary cancer, respectively, withPalbociclib monotherapy does not have clinical activity in patients with advanced pancreatic or biliary cancers with

TAPUR is a pragmatic, phase II basket study evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known to be drug targets. Sunitinib is an oral multikinase inhibitor of FMS-like tyrosine kinase-3 (FLT-3), among other targets. Results from a cohort of patients with metastatic colorectal cancer (mCRC) with FLT-3 amplification treated with sunitinib are reported. This study aimed to investigate whether patients with mCRC with FLT-3 amplification would be responsive to sunitinib, an oral multikinase inhibitor. Eligible patients received a standard sunitinib dose of 50 mg orally for 4 weeks followed by 2 weeks off. Simon’s two-stage design was used with the primary study endpoint of objective response (OR) or stable disease (SD) at 16 weeks based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints were progression-free survival, overall survival, and safety. Ten patients were enrolled from November 2016 to April 2018. All patients had mCRC with FLT-3 amplification. No ORs were observed. Although two patients had SD at 16 weeks, one died because of disease progression shortly thereafter and the cohort was closed. A single grade 3 adverse event of diarrhea was reported as possibly related to sunitinib. Monotherapy with sunitinib does not have clinical activity in patients with mCRC with FLT-3 amplification and should not be prescribed for off-label use. Other treatments should be considered for these patients, including treatments offered in clinical trials. NCT02693535 (26 February 2016).

The Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a phase II pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancer with genomic alterations known to be drug targets. Results in a cohort of patients with non-small-cell lung cancer (NSCLC) withEligible patients were ≥ 18 years old with advanced NSCLC, no remaining standard treatment options, measurable disease, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function. Patients with NSCLC withTwenty-nine patients were enrolled from January 2017 to June 2018; two patients were not evaluable for response but were included in safety analyses. One patient with partial response and six patients with SD were observed, for a disease control rate of 31% (90% CI, 19% to 40%). Median PFS was 8.1 weeks (95% CI, 7.1 to 16.0 weeks), and median OS was 21.6 weeks (95% CI, 14.1 to 41.1 weeks). Eleven patients had at least 1 grade 3 or 4 adverse event (AE) or serious AE (SAE) possibly related to palbociclib (most common, cytopenias). Other AEs or SAEs possibly related to the treatment included anorexia, fatigue, febrile neutropenia, hypophosphatemia, sepsis, and vomiting.Palbociclib monotherapy demonstrated evidence of modest antitumor activity in heavily pretreated patients with NSCLC with

PURPOSEThe Targeted Agent and Profiling Utilization Registry (TAPUR) Study identifies signals of antitumor activity of commercially available targeted agents in patients with advanced cancers that harbor genomic alterations known as drug targets. In this article, data from two cohorts of patients with pancreatic and biliary cancers with CDKN2A loss or mutation treated with palbociclib are reported.METHODSEligible patients age 12 years and older with advanced measurable or evaluable solid tumors are provided treatment according to protocol-specified genomic matching rules. The primary study end point is objective response or stable disease of at least 16 weeks duration. For each cohort, a Simon two-stage design was used with a futility evaluation after 10 patients. Secondary end points include safety, progression-free survival (PFS), and overall survival (OS).RESULTSBetween July 2016 and November 2017, 12 and 10 patients with pancreatic and biliary cancer, respectively, with CDKN2A loss or mutation were treated with palbociclib. Twenty evaluable patients (10 per cohort) were included in the analysis. No patients had objective response or stable disease at 16 weeks, and both cohorts were closed. Two patients, neither with response, were determined to be ineligible. All patients were evaluated for safety, PFS, and OS. A median PFS of 7.2 weeks (90% CI, 4.0 to 8.0 weeks) and median OS of 12.4 weeks (90% CI, 4.7 to 23.1 weeks) were observed in the pancreatic cohort. A median PFS of 7.3 weeks (90% CI, 3.9 to 7.9 weeks) and median OS of 11.1 weeks (90% CI, 5.1 to 14.0 weeks) were observed in the biliary cohort. No unexpected toxicities were observed.CONCLUSIONPalbociclib monotherapy does not have clinical activity in patients with advanced pancreatic or biliary cancers with CDKN2A loss or mutation. Toxicity is similar to reported experience with palbociclib in other tumor types.

TAPUR is a pragmatic, phase II basket study evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known to be drug targets. Sunitinib is an oral multikinase inhibitor of FMS-like tyrosine kinase-3 (FLT-3), among other targets. Results from a cohort of patients with metastatic colorectal cancer (mCRC) with FLT-3 amplification treated with sunitinib are reported.This study aimed to investigate whether patients with mCRC with FLT-3 amplification would be responsive to sunitinib, an oral multikinase inhibitor.Eligible patients received a standard sunitinib dose of 50 mg orally for 4 weeks followed by 2 weeks off. Simon's two-stage design was used with the primary study endpoint of objective response (OR) or stable disease (SD) at 16 weeks based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints were progression-free survival, overall survival, and safety.Ten patients were enrolled from November 2016 to April 2018. All patients had mCRC with FLT-3 amplification. No ORs were observed. Although two patients had SD at 16 weeks, one died because of disease progression shortly thereafter and the cohort was closed. A single grade 3 adverse event of diarrhea was reported as possibly related to sunitinib.Monotherapy with sunitinib does not have clinical activity in patients with mCRC with FLT-3 amplification and should not be prescribed for off-label use. Other treatments should be considered for these patients, including treatments offered in clinical trials.NCT02693535 (26 February 2016).

BACKGROUND The Affordable Care Act (ACA) includes a mandate requiring most private health insurers to cover routine patient care costs for cancer clinical trial participation; however, the impact of this provision on cancer centers’ efforts to accrue patients to clinical trials has not been well described. METHODS First, members of cancer research centers and community-based institutions (n = 252) were surveyed to assess the status of insurance denials, and then, a focused survey (n = 77) collected denial details. Univariate and multivariate analyses were used to examine associations between the receipt of denials and site characteristics. RESULTS Overall, 62.7% of the initial survey respondents reported at least 1 insurance denial during 2014. Sites using a precertification process were 3.04 times more likely to experience denials (95% confidence interval, 1.55-5.99; P ≤ .001), and similar rates of denials were reported from sites located in states with preexisting clinical trial coverage laws versus states without them (82.3% vs 85.1%; χ[2] = 50.7; P ≤ .001). Among the focused survey sites, academic centers reported denials more often than community sites (71.4% vs 46.4%). The failure of plans to cover trial participation was cited as the most common reason provided for denials (n = 33 [80.5%]), with nearly 80% of sites (n = 61) not receiving a coverage response from the insurer within 72 hours. CONCLUSIONS Despite the ACA's mandate for most insurers to cover routine care costs for cancer clinical trial participation, denials and delays continue. Denials may continue because some insurers remain exempt from the law, or they may signal an implementation failure. Delays in coverage may affect patient participation in trials. Additional efforts to eliminate this barrier will be needed to achieve federal initiatives to double the pace of cancer research over the next 5 years. Future work should assess the law's effectiveness at the patient level to inform these efforts. Cancer 2017;123:2893–900. © 2017 American Cancer Society.

The Affordable Care Act (ACA) includes a mandate requiring most private health insurers to cover routine patient care costs for cancer clinical trial participation; however, the impact of this provision on cancer centers' efforts to accrue patients to clinical trials has not been well described.First, members of cancer research centers and community-based institutions (n = 252) were surveyed to assess the status of insurance denials, and then, a focused survey (n = 77) collected denial details. Univariate and multivariate analyses were used to examine associations between the receipt of denials and site characteristics.Overall, 62.7% of the initial survey respondents reported at least 1 insurance denial during 2014. Sites using a precertification process were 3.04 times more likely to experience denials (95% confidence interval, 1.55-5.99; P ≤ .001), and similar rates of denials were reported from sites located in states with preexisting clinical trial coverage laws versus states without them (82.3% vs 85.1%; χ = 50.7; P ≤ .001). Among the focused survey sites, academic centers reported denials more often than community sites (71.4% vs 46.4%). The failure of plans to cover trial participation was cited as the most common reason provided for denials (n = 33 [80.5%]), with nearly 80% of sites (n = 61) not receiving a coverage response from the insurer within 72 hours.Despite the ACA's mandate for most insurers to cover routine care costs for cancer clinical trial participation, denials and delays continue. Denials may continue because some insurers remain exempt from the law, or they may signal an implementation failure. Delays in coverage may affect patient participation in trials. Additional efforts to eliminate this barrier will be needed to achieve federal initiatives to double the pace of cancer research over the next 5 years. Future work should assess the law's effectiveness at the patient level to inform these efforts. Cancer 2017;123:2893-900. © 2017 American Cancer Society.

Background: TAPUR is a phase II multi-basket study evaluating the anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations known to be drug targets. S is an oral multi-kinase inhibitor that inhibits Fms-like tyrosine kinase-3 (FLT-3) in biochemical and cellular assays. Results from mCRC pts each with FLT-3 amplification treated with S are reported. Methods: Simon’s optimal two stage design was used to test the null hypothesis of 15% response rate versus the alternative of 35%. Power and alpha were set at 85% and 10%, respectively. Response was assessed per RECIST v1.1. This design requires 10 pts in stage 1 and if Results: Ten pts were enrolled from November 2016 to April 2018. Pts received S at a dose of 50 mg orally once daily for four weeks followed by two weeks off. All pts had mCRC with FLT-3 amplification. All pts are included in the data analysis for demographics, safety, PFS and OS (Table 1). No ORs were observed and despite observation of 2 pts with SD at 16 wks, the cohort was closed after further examination revealed both pts with SD died due to disease progression shortly after the 16 wk evaluation. Grades 3-4 AEs at least possibly related to drug are required to be reported. A single grade 3 diarrhea was reported as possibly related to S. Conclusions: Monotherapy with S does not have sufficient clinical activity in mCRC pts with FLT-3 amplification for continued evaluation in this pt population. Other treatments should be considered for these pts, including treatments offered in clinical trials. Table 1:Baseline demographics, clinical characteristics and outcomes by cohortSunitinib targeting FLT-3Tumor TypemCRC (N=10)Median age, yrs (range)56 (41, 71)Male, %80ECOG Performance Status, %01230700Median PFS, wks (90% CI)10.1 (7.4, 15.9)Median OS, wks (90% CI)29.5 (15.7, 39.9)Drug-related AEs, grades 3-4 (% of pts)10 Citation Format: Ricardo H. Alvarez, Elizabeth Garrett-Mayer, Susan Halabi, Pam K. Mangat, Tareq Al Baghdadi, Eugene R. Ahn, Seungjean Chai, Andrew L. Rygiel, Kaitlyn R. Antonelli, Samiha Islam, Suanna S. Bruinooge, Richard L. Schilsky. Sunitinib (S) in patients (Pts) with metastatic colorectal cancer (mCRC) with FLT-3 alterations: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT146.

Background: The TAPUR Study is a phase II multi-basket study that evaluates the anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations known to be drug targets. Results in two cohorts of BC and NSCLC pts each without reported KRAS, NRAS, BRAF mutationstreated with C are reported. Methods: Simon’s optimal two stage design was used to test the null hypothesis of 15% response rate versus the alternative of 35%. Power and alpha were set at 85% and 10%, respectively. Response was assessed per RECIST v1.1. This design requires 10 pts in stage 1 and if Results: Ten pts were enrolled in the BC cohort from June 2016 to May 2018. Ten pts were enrolled in the NSCLC cohort from January 2017 to May 2018. Pts received C at an initial intravenous infusion of 400 mg/m2 over 120 minutes and subsequent weekly infusions of 250 mg/m2 over 60 minutes. All pts are included in the data analysis for demographics, safety, PFS and OS (Table 1). No ORs or SD at 16 wks were observed in either cohort and both were therefore closed. Grades 3-4 adverse events (AEs) at least possibly related to drug are required to be reported. A single grade 3 AE of hypomagnesemia was reported in the NSCLC cohort as possibly related to C. Conclusions: Results from these cohorts suggest monotherapy with C does not have clinical activity in BC or NSCLC pts without reported KRAS, NRAS, BRAF mutations. Other treatments should be considered for these pts, including treatments offered in clinical trials. Table 1:Baseline demographics, clinical characteristics and outcomes by cohortCetuximab targeting tumors without reported KRAS, NRAS, BRAF mutationsTumor TypeBC (N=10)NSCLC (N=10)Median age, yrs (range)59 (45, 65)60 (55, 82)Male, %060ECOG Performance Status, %01260301010900Median PFS, wks (90% CI)6.7 (4.0, 7.9)8.0 (7.6, 8.4)Median OS, wks (90% CI)11.0 (4.9, 30.1)19.6 (8.6, 25.6)Drug-related AEs, grades 3-4 (% of pts)010 Citation Format: Julie Fisher, Elizabeth Garrett-Mayer, Susan Halabi, Pam K. Mangat, Ricardo H. Alvarez, Timothy L. Cannon, Pamela Crilley, Theodore Pollock, Tareq Al Baghdadi, Jared A. Cotta, Andrew L. Rygiel, Kaitlyn R. Antonelli, Samiha Islam, Suanna S. Bruinooge, Richard L. Schilsky. Cetuximab (C) in patients (Pts) with breast cancer (BC) and non-small cell lung cancer (NSCLC) without reported KRAS, NRAS, BRAF mutations: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT135.

9041 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of NSCLC pts with CDKN2A loss or mutation treated with P are reported. Methods: Eligible pts had advanced NSCLC, no standard treatment options, measurable disease, ECOG PS 0-2 and adequate organ function. Genomic testing was performed using commercially available tests. Pts matched to P had NSCLC with CDKN2A loss or mutation and no RB mutations. A Simon two-stage design was used to test a null rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have disease control (DC) (objective response (OR) or stable disease at 16 weeks (wks) (SD16+)), an additional 18 pts are enrolled. If ≥7 of 28 pts have DC, the drug is considered worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Twenty-nine pts were enrolled from January 2017 to June 2018; 1 pt was unevaluable for response but is included in safety analyses. Pts received P at 125 mg orally once daily for 21 days, followed by 7 days off. Demographics and outcomes are summarized in Table (N = 28). One PR and 6 SD16+ were observed for a DC rate of 29% (90% CI, 15% to 37%). 10 pts had at least one grade 3 or 4 AE or SAE at least possibly related to P with the most common being cytopenias. Other grade 3-4 AEs or SAEs at least possibly related to P included fatigue, anorexia, febrile neutropenia, myocardial infarction, sepsis, vomiting, and hypophosphatemia. Conclusions: Monotherapy with P demonstrated evidence of anti-tumor activity in heavily pre-treated NSCLC pts with CDKN2A loss or mutation . Additional study is warranted to confirm the efficacy of P in pts with NSCLC with CDKN2A loss or mutation. Clinical trial information: NCT02693535. [Table: see text]

1014 Background: TAPUR is a phase II basket study evaluating the anti-tumor activity of commercially available targeted agents in pts with advanced cancers with specific genomic alterations. P is an immune checkpoint inhibitor and HTMB is an emerging predictive biomarker for checkpoint inhibitor therapy. Results in a cohort of MBC pts with HTMB treated with P are reported. Methods: Eligible pts had advanced cancer, no standard treatment options, ECOG PS 0-1, measurable disease and acceptable organ function. Genomic testing was performed using commercially available tests selected by sites. Pts matched to P had HTMB defined as ≥9 mutations/megabase (Muts/Mb) by a FoundationOne test (n=20) or approved by the TAPUR Molecular Tumor Board for other tests (n=8). A Simon two-stage design was used to test a null rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have disease control (DC) (objective response (OR) or stable disease at 16 weeks (wks) (SD16+)), an additional 18 pts are enrolled. If ≥7 of 28 pts have DC, the drug is considered worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Twenty-eight female MBC pts were enrolled from October 2016 to July 2018. Pts received P at 2 mg/kg (n=8) or 200 mg (n=20) IV over 30 minutes, every 3 wks. HTMB ranged from 9 to 37 Muts/Mb. Demographics and outcomes are summarized in Table (N=28). No relationship was observed between #Muts/Mb and PFS or OS. Two grade 3 AEs (weight loss and hypoalbuminemia) and 1 grade 2 SAE (urinary tract infection) were reported as at least possibly related to P. Conclusions: P demonstrated anti-tumor activity in heavily pre-treated MBC pts with HTMB . Additional study of P is warranted in MBC pts with HTMB. Clinical trial information: NCT02693535. [Table: see text]

2532Background: The TAPUR Study is a phase II multi‐basket study that evaluates the anti‐tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alteratio...

e14047Background: A recent federal initiative, the Cancer Moonshot, to develop and complete randomized clinical trials in four years for tens of thousands of US cancer patients may face a hurdle. A...