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

The University of Chicago

Residency, Medicine

University of Washington

Fellowship in Hematology-Oncology, Medicine

Duke University School of Medicine

Grants:

A Phase 1/1b first-in-human dose escalation and expansion study for theevaluation of safety, pharmacokinetics, pharmacodynamics and anti-tumor activity of SAR439459 administered intravenously as monotherapy and in combination with REGN2810 in adult

Administered By
Duke Cancer Institute
Awarded By
Sanofi US
Role
Principal Investigator
Start Date
End Date

A Phase 1 Open-label Dose Escalation and Dose Expansion Study of CGX1321 in Subjects with Advanced Solid Tumors and Phase 1b Study of CGX1321 in Combination with Pembrolizumab in Subjects with Advanced Gastrointestinal Tumors

Administered By
Duke Cancer Institute
Awarded By
Curegenix Inc.
Role
Principal Investigator
Start Date
End Date

A PHASE Ib, MULTICENTER, OPEN-LABELSTUDY TO EVALUATE THE SAFETY, EFFICACY, AND PHARMACOKINETICS OF CIBISATAMAB IN COMBINATION WITH ATEZOLIZUMAB AFTER PRETREATMENT WITH OBINUTUZUMAB IN PATIENTS WITH PREVIOUSLY TREATED METASTATIC, MICROSATELLITE-STABL

Administered By
Duke Cancer Institute
Awarded By
Genentech, Inc.
Role
Principal Investigator
Start Date
End Date

A PHASE 1/2, OPEN-LABEL, MULTICENTER, DOSE ESCALATION AND DOSE EXPANSION STUDY OF NKTR-262 IN COMBINATION WITH NKTR-214 AND IN COMBINATION WITH NKTR-214 PLUS NIVOLUMAB IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC SOLID TUMOR MALIGNANCIES

Administered By
Duke Cancer Institute
Awarded By
Nektar Therapeutics
Role
Principal Investigator
Start Date
End Date

Phase 2 Study Comparing Efficacy and Safety of ABT-165 plus FOLFIRI vs Bevacizumab plus FOLFIRI in Metastatic Colorectal Cancer Previously Treated with Fluoropyrimidine/Oxaliplatin and Bevacizumab

Administered By
Duke Cancer Institute
Awarded By
AbbVie Inc.
Role
Principal Investigator
Start Date
End Date

Publications:

First-In-Human, First-In-Class, Phase I Trial of the Fucosylation Inhibitor SGN-2FF in Patients with Advanced Solid Tumors.

<h4>Lessons learned</h4>Inhibition of glycoprotein fucosylation, as monotherapy and in combination with immune checkpoint blockade, is a promising therapeutic strategy for treating a broad range of cancers. In this first-in-human, first-in-class, phase I study in advanced solid tumors, SGN-2FF demonstrated dose-proportional pharmacokinetics, evidence of pharmacodynamic target inhibition of glycoprotein fucosylation, and preliminary antitumor activity. SGN-2FF was associated with thromboembolic events that led to study termination.<h4>Background</h4>We conducted a first-in-human, first-in-class, phase I study of SGN-2FF, a potent small-molecule inhibitor of glycoprotein fucosylation, in patients with advanced solid tumors.<h4>Methods</h4>The study consisted of four parts: SGN-2FF monotherapy dose-escalation (part A) and expansion (part B), and SGN-2FF + pembrolizumab dose-escalation (part C) and expansion (part D). The objectives were to evaluate safety and tolerability, maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of SGN-2FF monotherapy and SGN-2FF + pembrolizumab.<h4>Results</h4>Forty-six patients were enrolled (part A, n = 33; part B, n = 6; part C, n = 7; part D did not enroll any patients). During part A (n = 32) exploring 1-15 g once daily (QD) and 2-5 g twice daily (b.i.d.), grade 3 dose-limiting toxicities were diarrhea (2 g and 15 g QD) and increased lipase (2 g QD). The MTD was 10 g daily. In part A, common toxicities were grades 1-2 diarrhea, fatigue, and nausea (each 47%); thromboembolic events (grades 2-5) occurred in 5 of 32 patients (16%). Safety measures included concurrent prophylactic anticoagulation with low-molecular weight heparin (LMWH). In part C, despite the safety measures implemented, a thromboembolic event occurred in one of seven patients (14%) during the SGN-2FF lead-in period. Of 28 evaluable patients in part A, 1 patient with advanced head and neck squamous cell carcinoma achieved Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 complete response (CR) and 10 (36%) had RECIST v1.1 stable disease, including 1 patient with advanced triple-negative breast cancer with 51% tumor burden reduction. SGN-2FF administration led to dose-proportional increases in exposure and PD reduction in protein fucosylation.<h4>Conclusion</h4>SGN-2FF demonstrated proof-of-mechanism and preliminary antitumor activity but was associated with thromboembolic events leading to study termination.
Authors
Do, KT; Chow, LQM; Reckamp, K; Sanborn, RE; Burris, H; Robert, F; Camidge, DR; Steuer, CE; Strickler, JH; Weise, A; Specht, JM; Gutierrez, M; Haughney, P; Hengel, S; Derleth, CL; Yap, TA
MLA Citation
Do, Khanh T., et al. “First-In-Human, First-In-Class, Phase I Trial of the Fucosylation Inhibitor SGN-2FF in Patients with Advanced Solid Tumors.The Oncologist, July 2021. Epmc, doi:10.1002/onco.13911.
URI
https://scholars.duke.edu/individual/pub1488775
PMID
34288257
Source
epmc
Published In
The Oncologist
Published Date
DOI
10.1002/onco.13911

PD-1 MOUNTAINEER: Open-label, phase 2 study of tucatinib combined with trastuzumab for HER2-positive metastatic colorectal cancer (SGNTUC-017, trial in progress)

Authors
Siena, S; Elez, E; Peeters, M; André, T; Van den Eynde, M; Ng, K; Cercek, A; Fountzilas, C; Sanchez, F; Hubbard, J; Wu, C; Tabernero, J; Kardosh, A; Saeed, A; Strickler, J; Bekaii-Saab, T; Stecher, M; Palanca-Wessels, M; Van Cutsem, E
MLA Citation
Siena, S., et al. “PD-1 MOUNTAINEER: Open-label, phase 2 study of tucatinib combined with trastuzumab for HER2-positive metastatic colorectal cancer (SGNTUC-017, trial in progress).” Annals of Oncology, vol. 32, Elsevier BV, 2021, pp. S199–S199. Crossref, doi:10.1016/j.annonc.2021.05.019.
URI
https://scholars.duke.edu/individual/pub1488942
Source
crossref
Published In
Annals of Oncology
Volume
32
Published Date
Start Page
S199
End Page
S199
DOI
10.1016/j.annonc.2021.05.019

P-174 MOUNTAINEER-02: Phase 2/3 study of tucatinib, trastuzumab, ramucirumab, and paclitaxel in previously treated HER2+ gastric or gastroesophageal junction adenocarcinoma: Trial in progress

Authors
Strickler, J; Nakamura, Y; Shitara, K; Catenacci, D; Janjigian, Y; Barzi, A; Bekaii-Saab, T; Lenz, H; Lee, J; Van Cutsem, E; Chung, H; Tabernero, J; Yoshino, T; Siena, S; Garrido-Mayor, J; Palanca-Wessels, M; Xie, D; Marshall, J
MLA Citation
Strickler, J., et al. “P-174 MOUNTAINEER-02: Phase 2/3 study of tucatinib, trastuzumab, ramucirumab, and paclitaxel in previously treated HER2+ gastric or gastroesophageal junction adenocarcinoma: Trial in progress.” Annals of Oncology, vol. 32, Elsevier BV, 2021, pp. S159–S159. Crossref, doi:10.1016/j.annonc.2021.05.229.
URI
https://scholars.duke.edu/individual/pub1489185
Source
crossref
Published In
Annals of Oncology
Volume
32
Published Date
Start Page
S159
End Page
S159
DOI
10.1016/j.annonc.2021.05.229

P-111 PERSPECTIVE: Tepotinib plus cetuximab in patients with RAS/BRAF wild-type left-sided metastatic colorectal cancer and acquired resistance to anti-EGFR antibody therapy due to MET amplification

Authors
Tabernero, J; Bekaii-Saab, T; Safont Aguilera, M; Cubillo, A; Garcia-Carbonero, R; Limon, L; Rodríguez-Salas, N; Tournigand, C; Borg, C; Raghav, K; Finley, G; Strickler, J; Beier, F; Salim, S; Esser, R; Liu, E; Adrian, S; López-López, C
MLA Citation
Tabernero, J., et al. “P-111 PERSPECTIVE: Tepotinib plus cetuximab in patients with RAS/BRAF wild-type left-sided metastatic colorectal cancer and acquired resistance to anti-EGFR antibody therapy due to MET amplification.” Annals of Oncology, vol. 32, Elsevier BV, 2021, pp. S136–37. Crossref, doi:10.1016/j.annonc.2021.05.166.
URI
https://scholars.duke.edu/individual/pub1489186
Source
crossref
Published In
Annals of Oncology
Volume
32
Published Date
Start Page
S136
End Page
S137
DOI
10.1016/j.annonc.2021.05.166

Implementation of a Molecular Tumor Registry to Support the Adoption of Precision Oncology Within an Academic Medical Center: The Duke University Experience.

Comprehensive genomic profiling to inform targeted therapy selection is a central part of oncology care. However, the volume and complexity of alterations uncovered through genomic profiling make it difficult for oncologists to choose the most appropriate therapy for their patients. Here, we present a solution to this problem, The Molecular Registry of Tumors (MRT) and our Molecular Tumor Board (MTB). PATIENTS AND METHODS: MRT is an internally developed system that aggregates and normalizes genomic profiling results from multiple sources. MRT serves as the foundation for our MTB, a team that reviews genomic results for all Duke University Health System cancer patients, provides notifications for targeted therapies, matches patients to biomarker-driven trials, and monitors the molecular landscape of tumors at our institution. RESULTS: Among 215 patients reviewed by our MTB over a 6-month period, we identified 176 alterations associated with therapeutic sensitivity, 15 resistance alterations, and 51 alterations with potential germline implications. Of reviewed patients, 17% were subsequently treated with a targeted therapy. For 12 molecular therapies approved during the course of this work, we identified between two and 71 patients who could qualify for treatment based on retrospective MRT data. An analysis of 14 biomarker-driven clinical trials found that MRT successfully identified 42% of patients who ultimately enrolled. Finally, an analysis of 4,130 comprehensive genomic profiles from 3,771 patients revealed that the frequency of clinically significant therapeutic alterations varied from approximately 20% to 70% depending on the tumor type and sequencing test used. CONCLUSION: With robust informatics tools, such as MRT, and the right MTB structure, a precision cancer medicine program can be developed, which provides great benefit to providers and patients with cancer.
Authors
Green, MF; Bell, JL; Hubbard, CB; McCall, SJ; McKinney, MS; Riedel, JE; Menendez, CS; Abbruzzese, JL; Strickler, JH; Datto, MB
MLA Citation
URI
https://scholars.duke.edu/individual/pub1497103
PMID
34568718
Source
pubmed
Published In
Jco Precision Oncology
Volume
5
Published Date
DOI
10.1200/PO.21.00030