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:

Anti-EGFR-resistant clones decay exponentially after progression: implications for anti-EGFR re-challenge.

BACKGROUND: Colorectal cancer (CRC) has been shown to acquire RAS and EGFR ectodomain mutations as mechanisms of resistance to epidermal growth factor receptor (EGFR) inhibition (anti-EGFR). After anti-EGFR withdrawal, RAS and EGFR mutant clones lack a growth advantage relative to other clones and decay; however, the kinetics of decay remain unclear. We sought to determine the kinetics of acquired RAS/EGFR mutations after discontinuation of anti-EGFR therapy. PATIENTS AND METHODS: We present the post-progression circulating tumor DNA (ctDNA) profiles of 135 patients with RAS/BRAF wild-type metastatic CRC treated with anti-EGFR who acquired RAS and/or EGFR mutations during therapy. Our validation cohort consisted of an external dataset of 73 patients with a ctDNA profile suggestive of prior anti-EGFR exposure and serial sampling. A separate retrospective cohort of 80 patients was used to evaluate overall response rate and progression free survival during re-challenge therapies. RESULTS: Our analysis showed that RAS and EGFR relative mutant allele frequency decays exponentially (r2=0.93 for RAS; r2=0.94 for EGFR) with a cumulative half-life of 4.4 months. We validated our findings using an external dataset of 73 patients with a ctDNA profile suggestive of prior anti-EGFR exposure and serial sampling, confirming exponential decay with an estimated half-life of 4.3 months. A separate retrospective cohort of 80 patients showed that patients had a higher overall response rate during re-challenge therapies after increasing time intervals, as predicted by our model. CONCLUSION: These results provide scientific support for anti-EGFR re-challenge and guide the optimal timing of re-challenge initiation.
Authors
Parseghian, CM; Loree, JM; Morris, VK; Liu, X; Clifton, KK; Napolitano, S; Henry, JT; Pereira, AA; Vilar, E; Johnson, B; Kee, B; Raghav, K; Dasari, A; Wu, J; Garg, N; Raymond, VM; Banks, KC; Talasaz, AA; Lanman, RB; Strickler, JH; Hong, DS; Corcoran, RB; Overman, MJ; Kopetz, S
MLA Citation
Parseghian, C. M., et al. “Anti-EGFR-resistant clones decay exponentially after progression: implications for anti-EGFR re-challenge.Ann Oncol, vol. 30, no. 2, Feb. 2019, pp. 243–49. Pubmed, doi:10.1093/annonc/mdy509.
URI
https://scholars.duke.edu/individual/pub1428918
PMID
31987421
Source
pubmed
Published In
Ann Oncol
Volume
30
Published Date
Start Page
243
End Page
249
DOI
10.1093/annonc/mdy509

Phase I Dose-Escalation and -Expansion Study of Telisotuzumab (ABT-700), an Anti-c-Met Antibody, in Patients with Advanced Solid Tumors.

This first-in-human phase I study evaluated the pharmacokinetics, safety, and preliminary efficacy of telisotuzumab, formerly called ABT-700, an antagonistic antibody directed against c-Met. For dose escalation (3+3 design), 3 to 6 patients with advanced solid tumors were enrolled into four dose cohorts (5-25 mg/kg). In the dose-expansion phase, a subset of patients was prospectively selected for MET amplification (FISH screening). Patients received telisotuzumab intravenously on day 1 every 21 days. For dose expansion, 15 mg/kg was chosen as the dose on the basis of safety, pharmacokinetics, and other data from the escalation cohorts. Forty-five patients were enrolled and received at least one dose of telisotuzumab (dose escalation, n = 15; dose expansion, n = 30). Telisotuzumab showed a linear pharmacokinetics profile; peak plasma concentration was proportional to dose level. There were no acute infusion reactions and no dose-limiting toxicities were observed. The most common treatment-related adverse events included hypoalbuminemia (n = 9, 20.0%) and fatigue (n = 5, 11.1%). By Response Evaluation Criteria In Solid Tumors (RECIST), 4 of 10 (40.0%) patients with MET-amplified tumors had confirmed partial response in target lesions (one ovarian, two gastric, and one esophageal), two (20.0%) had stable disease, three (30.0%) had progressive disease; one patient was unable to be evaluated. Among patients with nonamplified tumors (n = 35), no objective responses were observed; however, 11 patients had stable disease per RECIST criteria. In conclusion, telisotuzumab has an acceptable safety profile with clinical activity observed in patients with MET-amplified advanced solid tumors.
Authors
Strickler, JH; LoRusso, P; Salgia, R; Kang, Y-K; Yen, CJ; Lin, C-C; Ansell, P; Motwani, M; Wong, S; Yue, H; Wang, L; Reilly, E; Afar, D; Naumovski, L; Ramanathan, RK
MLA Citation
Strickler, John H., et al. “Phase I Dose-Escalation and -Expansion Study of Telisotuzumab (ABT-700), an Anti-c-Met Antibody, in Patients with Advanced Solid Tumors.Mol Cancer Ther, vol. 19, no. 5, May 2020, pp. 1210–17. Pubmed, doi:10.1158/1535-7163.MCT-19-0529.
URI
https://scholars.duke.edu/individual/pub1434154
PMID
32127466
Source
pubmed
Published In
Mol Cancer Ther
Volume
19
Published Date
Start Page
1210
End Page
1217
DOI
10.1158/1535-7163.MCT-19-0529

Overcoming Resistance to Targeted Therapies in Gastrointestinal Cancers: Progress to Date and Progress to Come.

Targeted therapies have transformed the treatment paradigm in diseases such as non-small cell lung cancer and melanoma but have shown relatively modest clinical benefit in gastrointestinal malignancies. Anti-EGFR therapy in RAS wild-type colorectal cancer, anti-HER2 therapy in HER2- amplified esophagogastric cancer, and FGFR and isocitrate dehydrogenase 1 (IDH1) inhibitors in FGFR2 fusion-positive and IDH1-mutant biliary tract cancers offer antitumor efficacy, but the clinical benefit and durability of response in each case are typically limited. We review targeted therapies in each of these therapeutic areas and discuss their clinical efficacy, mechanisms of primary and acquired resistance, and strategies to overcome this resistance. We discuss lessons learned that we hope will lead to an expanded role for molecularly targeted therapy options for patients with gastrointestinal cancers.
Authors
Chen, C; Di Bartolomeo, M; Corallo, S; Strickler, JH; Goyal, L
MLA Citation
Chen, Christopher, et al. “Overcoming Resistance to Targeted Therapies in Gastrointestinal Cancers: Progress to Date and Progress to Come.American Society of Clinical Oncology Educational Book. American Society of Clinical Oncology. Annual Meeting, vol. 40, May 2020, pp. 161–73. Epmc, doi:10.1200/edbk_280871.
URI
https://scholars.duke.edu/individual/pub1441594
PMID
32421451
Source
epmc
Published In
American Society of Clinical Oncology Educational Book. American Society of Clinical Oncology. Meeting
Volume
40
Published Date
Start Page
161
End Page
173
DOI
10.1200/edbk_280871

Safety, efficacy and pharmacodynamics (PD) of MEDI9447 (oleclumab) alone or in combination with durvalumab in advanced colorectal cancer (CRC) or pancreatic cancer (panc).

Authors
Overman, MJ; LoRusso, P; Strickler, JH; Patel, SP; Clarke, SJ; Noonan, AM; Prasanna, T; Amin, MA; Nemunaitis, JJ; Desai, J; O'Byrne, KJ; George, TJ; Englert, J; She, D; Cooper, ZA; Wu, Y; Khan, A; Kumar, R; Bendell, JC
MLA Citation
Overman, Michael J., et al. “Safety, efficacy and pharmacodynamics (PD) of MEDI9447 (oleclumab) alone or in combination with durvalumab in advanced colorectal cancer (CRC) or pancreatic cancer (panc).Journal of Clinical Oncology, vol. 36, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2018, pp. 4123–4123. Crossref, doi:10.1200/jco.2018.36.15_suppl.4123.
URI
https://scholars.duke.edu/individual/pub1441728
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
36
Published Date
Start Page
4123
End Page
4123
DOI
10.1200/jco.2018.36.15_suppl.4123

Tumor mutational burden (TMB) as a predictive biomarker of immune checkpoint blockade (ICB) in metastatic solid tumors

Authors
MLA Citation
Kao, Chester, et al. “Tumor mutational burden (TMB) as a predictive biomarker of immune checkpoint blockade (ICB) in metastatic solid tumors.” Journal of Clinical Oncology, vol. 38, no. 5, AMER SOC CLINICAL ONCOLOGY, 2020.
URI
https://scholars.duke.edu/individual/pub1441335
Source
wos
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
38
Published Date