John Strickler

Positions:

Associate Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2005

University of Chicago

Residency, Medicine

University of Washington

Fellowship in Hematology-Oncology, Medicine

Duke University School of Medicine

Grants:

CGX1321-101

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

CO40939

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

Nektar

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

AbbVie M14-064

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

AbbVie M16-438

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

Publications:

Safety, Efficacy, and Pharmacokinetics of AMG 510, a Novel KRAS(G12C) Inhibitor, in Patients with Non-Small Cell Lung Cancer

Authors
Govindan, R; Fakih, M; Price, T; Falchook, G; Desai, J; Kuo, J; Strickler, J; Krauss, J; Li, B; Denlinger, C; Durm, G; Ngang, J; Henary, H; Ngarmchamnanrith, G; Rasmussen, E; Morrow, PK; Hong, D
MLA Citation
Govindan, R., et al. “Safety, Efficacy, and Pharmacokinetics of AMG 510, a Novel KRAS(G12C) Inhibitor, in Patients with Non-Small Cell Lung Cancer.” Journal of Thoracic Oncology, vol. 14, no. 11, ELSEVIER SCIENCE INC, 2019, pp. S1125–26.
URI
https://scholars.duke.edu/individual/pub1421379
Source
wos
Published In
Journal of Thoracic Oncology
Volume
14
Published Date
Start Page
S1125
End Page
S1126

P2.15-C Phase 1 Trial Evaluating Safety, Efficacy, and PK of AMG 510, a Novel KRASG12C Inhibitor, in Non-Small Cell Lung Cancer

Authors
Govindan, R; Fakih, MG; Price, TJ; Falchook, GS; Desai, J; Kuo, JC; Strickler, JH; Krauss, JC; Li, BT; Denlinger, CS; Durm, G; Ngang, J; Henary, H; Ngarmchamnanrith, G; Rasmussen, E; Morrow, PK; Hong, DS
MLA Citation
Govindan, R., et al. “P2.15-C Phase 1 Trial Evaluating Safety, Efficacy, and PK of AMG 510, a Novel KRASG12C Inhibitor, in Non-Small Cell Lung Cancer.” Journal of Thoracic Oncology, vol. 14, no. 11, Elsevier BV, 2019, pp. S1191–92. Crossref, doi:10.1016/j.jtho.2019.09.181.
URI
https://scholars.duke.edu/individual/pub1421378
Source
crossref
Published In
Journal of Thoracic Oncology
Volume
14
Published Date
Start Page
S1191
End Page
S1192
DOI
10.1016/j.jtho.2019.09.181

Comprehensive landscape of gene amplifications (amps) in tissue and circulating tumor DNA (ctDNA) in metastatic colorectal cancer (mCRC).

<jats:p> 604 </jats:p><jats:p> Background: Amps, as oncogenic and resistance drivers, have therapeutic implications, but unlike mutations, have been sparsely described in mCRC. Functional account is piecemeal due to vague definitions, limited data on co-occurring alterations and use of primary tissue samples nonrepresentative of tumor heterogeneity. Our aim was to define the amp landscape in mCRC using tissue and ctDNA sequencing. Methods: We performed systematic analyses of copy-number variation in 2 cohorts of mCRC patients (pts) [tissue (TC) (N = 1,134) and ctDNA (BC) (N = 3,218)] who had high sensitivity targeted sequencing with MSK-IMPACT (341-468 genes) or Guardant Health (70-73 genes) panel, respectively. For BC, plasma copy number was adjusted (ApCN) to account for variable tumor DNA shedding using max allele frequency and high amp (HAmp) was defined as &gt; 4 copies (similar to predefined tissue cutoff). Results: 166 (15%) and 405 (13%) pts in TC and BC harbored amp in at least one of 18 genes assessed by both panels (Table). Amp prevalence for individual gene was similar in both cohorts ( r = 0.9; P &lt; .01) with RTK amps ( EGFR, ERBB2, MET, FGFR1/2, PDGFRA) seen in 8% pts. Key RTK amps were enriched in RAS/BRAF wild type (RB WT) compared to mutant (RB MUT) (OR 3.5; P &lt; .01) pts in both cohorts, in contrast to low prevalence RTK and non-RTK amps. Median ApCN was higher for RTKs in RB WT vs MUT cases ( ERBB2: 12 vs 5; P = .02). Using validated EGFRab exposure (EGFRi) ctDNA signature, we found that EGFRi pts had higher prevalence of EGFR, MET, BRAF, KRAS, PIK3CA and FGFR1 amps compared to EGFRab naïve pts. Conclusions: While individually uncommon, amps occur across key oncogenic pathways in mCRC and after adjusting for ctDNA shedding, are seen at similar prevalence in tissue and plasma. Amps in RTKs are seen in 10-12% of RB WT tumors, suggesting clinically relevant roles as oncogenic effectors and targets. After EGFRi, a number of amps emerge, including PIK3CA and FGFR1 amps, not previously implicated in acquired resistance. [Table: see text] </jats:p>
Authors
Raghav, KPS; Yaeger, R; Loree, JM; Dasari, A; Morris, VK; Kee, BK; Raymond, VM; Nagy, RJ; Lanman, RB; Strickler, JH; Corcoran, RB; Overman, MJ; Kopetz, S
MLA Citation
Raghav, Kanwal Pratap Singh, et al. “Comprehensive landscape of gene amplifications (amps) in tissue and circulating tumor DNA (ctDNA) in metastatic colorectal cancer (mCRC)..” Journal of Clinical Oncology, vol. 37, no. 4_suppl, American Society of Clinical Oncology (ASCO), 2019, pp. 604–604. Crossref, doi:10.1200/jco.2019.37.4_suppl.604.
URI
https://scholars.duke.edu/individual/pub1416459
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
37
Published Date
Start Page
604
End Page
604
DOI
10.1200/jco.2019.37.4_suppl.604

Addressing the Conundrum of Bleeding and Cancer Detection With Antithrombotic Therapies for Chronic Atherosclerotic Cardiovascular Disease.

Authors
Roe, MT; Strickler, J
MLA Citation
Roe, Matthew T., and John Strickler. “Addressing the Conundrum of Bleeding and Cancer Detection With Antithrombotic Therapies for Chronic Atherosclerotic Cardiovascular Disease..” Circulation, vol. 140, no. 18, Oct. 2019, pp. 1460–62. Pubmed, doi:10.1161/CIRCULATIONAHA.119.042875.
URI
https://scholars.duke.edu/individual/pub1417914
PMID
31657956
Source
pubmed
Published In
Circulation
Volume
140
Published Date
Start Page
1460
End Page
1462
DOI
10.1161/CIRCULATIONAHA.119.042875

ABT-165 plus FOLFIRI versus bevacizumab plus FOLFIRI in patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine/oxaliplatin and bevacizumab.

<jats:p> TPS720 </jats:p><jats:p> Background: Dual variable domain immunoglobulin ABT-165 targets human vascular endothelial growth factor (VEGF) and delta-like ligand 4 (DLL4). Combined VEGF and DLL4 blockade increased inhibition of subcutaneous xenograft growth of human colon cancer-derived cell lines versus blockade of either axis alone. In vivo, ABT-165 plus chemotherapy (CT) induced tumor regression with improved efficacy, vs anti-VEGF monoclonal antibody plus CT. In a phase 1 study, tolerable recommended phase 2 dose was identified for ABT-165 plus FOLFIRI and showed promising efficacy. This phase 2 trial in progress assesses efficacy/safety of ABT-165 plus FOLFIRI vs bevacizumab (bev) plus FOLFIRI in patients with second-line mCRC. Methods: This is an open-label, multicenter, phase 2 randomized (1:1) trial (NCT03368859) in patients (≥ 18 years; Eastern Cooperative performance status: 0–1) with histologically/cytologically confirmed mCRC who progressed after fluoropyrimidine/oxaliplatin and bev. ABT-165 (2.5 mg/kg) plus FOLFIRI (irinotecan: 180 mg/m<jats:sup>2</jats:sup>; leucovorin: 400 mg/m<jats:sup>2</jats:sup>; fluorouracil bolus: 400 mg/m<jats:sup>2</jats:sup>, infusion: 2400 mg/m<jats:sup>2</jats:sup>) or bev (5 mg/kg) plus FOLFIRI are given intravenously on day 1 of each 14-day cycle, until disease progression/intolerable toxicity. Primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS), objective response rate (ORR), and safety. Exploratory endpoints include biomarkers predictive for efficacy/safety, correlation of DLL4 levels with PFS, OS, and ORR, pharmacodynamic effects, and efficacy/safety-exposure relationships in ABT-165 arm. Hazard ratios of PFS and OS comparing the 2 groups are estimated using Cox proportional hazard model. Kaplan-Meier methodology is used to estimate PFS and OS curves, median PFS and OS, and their 90% confidence intervals. Safety is assessed by ABT-165 exposure, adverse events (AEs), serious AEs, all deaths, and changes in laboratory data and vital signs. Archival tissue is collected and evaluated for DLL4 expression and angiogenesis signature. Approximately 100 patients are planned to be enrolled, with recruitment initiated January 2018. Clinical trial information: NCT03368859. </jats:p>
Authors
Wainberg, ZA; Wang, L; Yue, H; Motwani, M; Kasichayanula, S; Blaney, ME; Naumovski, L; Strickler, JH
MLA Citation
Wainberg, Zev A., et al. “ABT-165 plus FOLFIRI versus bevacizumab plus FOLFIRI in patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine/oxaliplatin and bevacizumab..” Journal of Clinical Oncology, vol. 37, no. 4_suppl, American Society of Clinical Oncology (ASCO), 2019, pp. TPS720–TPS720. Crossref, doi:10.1200/jco.2019.37.4_suppl.tps720.
URI
https://scholars.duke.edu/individual/pub1416460
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
37
Published Date
Start Page
TPS720
End Page
TPS720
DOI
10.1200/jco.2019.37.4_suppl.tps720