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:

Diagnosis and Treatment of ERBB2-Positive Metastatic Colorectal Cancer: A Review.

Importance: Amplification of ERBB2 (formerly referred to as HER2) is present in nearly 3% of patients with metastatic colorectal cancer overall and 5% of patients with KRAS and NRAS wild-type tumors. Despite the availability of several ERBB2-targeted therapeutic options for patients with ERBB2-positive breast and gastric/gastroesophageal tumors, to date, there are currently no approved therapies for patients with ERBB2-positive metastatic colorectal cancer, although ERBB2-targeted therapies are recommended in National Comprehensive Cancer Network guidelines. Recent evidence indicates that anti-ERBB2 therapeutic strategies are active in patients with ERBB2-positive metastatic colorectal cancer and could potentially represent a new standard-of-care. Observations: The protein ERBB2 is a member of a family of epidermal growth factor receptors that also includes epidermal growth factor receptor (ERBB1), ERBB3, and ERBB4. Amplification of ERBB2 leads to overexpression of the ERBB2 tyrosine kinase receptor, resulting in aberrant signaling and cell migration, growth, adhesion, and differentiation. Colorectal tumors that harbor ERBB2 amplification are more likely to originate on the left side of the colon, are associated with primary and acquired resistance to anti-epidermal growth factor receptor therapies, and have increased incidence of central nervous system metastases. Using immunohistochemistry, fluorescence in situ hybridization, next-generation sequencing, and liquid biopsy techniques, several randomized clinical trials have evaluated the efficacy of ERBB2-targeted therapies in patients with ERBB2-positive metastatic colorectal cancer. These therapies include monoclonal antibodies, antibody-drug conjugates, and tyrosine kinase inhibitors, many of which were associated with favorable efficacy and safety profiles when treating patients with ERBB2-positive metastatic colorectal cancer. Conclusions and Relevance: The results of this review suggest the ERBB2 receptor is a promising target for patients with metastatic colorectal cancer; however, to date, no therapies are approved for use in this patient population. Therefore, it is imperative to continue to work to address this unmet need so that patients with ERBB2-positive metastatic colorectal cancer have therapeutic options should they become refractory to treatment with standard therapies.
Authors
Strickler, JH; Yoshino, T; Graham, RP; Siena, S; Bekaii-Saab, T
MLA Citation
Strickler, John H., et al. “Diagnosis and Treatment of ERBB2-Positive Metastatic Colorectal Cancer: A Review.Jama Oncol, vol. 8, no. 5, May 2022, pp. 760–69. Pubmed, doi:10.1001/jamaoncol.2021.8196.
URI
https://scholars.duke.edu/individual/pub1511996
PMID
35238866
Source
pubmed
Published In
Jama Oncol
Volume
8
Published Date
Start Page
760
End Page
769
DOI
10.1001/jamaoncol.2021.8196

Perioperative and Oncologic Outcomes of Hepatic Artery Infusion Pump Therapy at an Expanding HAI Program

Authors
Sharib, JM; Liu, A; Creasy, J; Wildman-Tobriner, B; Uronis, H; Hsu, D; Strickler, J; Zani, S; Allen, P; Lidsky, ME
MLA Citation
Sharib, Jeremy M., et al. “Perioperative and Oncologic Outcomes of Hepatic Artery Infusion Pump Therapy at an Expanding HAI Program.” Annals of Surgical Oncology, vol. 29, no. SUPPL 2, 2022, pp. 507–507.
URI
https://scholars.duke.edu/individual/pub1520984
Source
wos-lite
Published In
Annals of Surgical Oncology
Volume
29
Published Date
Start Page
507
End Page
507

A Phase 1a/b Open-Label, Dose-Escalation Study of Etigilimab Alone or in Combination with Nivolumab in Patients with Locally Advanced or Metastatic Solid Tumors.

PURPOSE: TIGIT (T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain) is a co-inhibitory receptor of T-cell and natural killer cell activity. Targeting TIGIT with or without PD-1/PD-L1 checkpoint inhibition may enhance antitumor immunity. PATIENTS AND METHODS: This Phase 1a/b trial was a first-in-human, open-label, multicenter, dose-escalation and -expansion study in patients with locally advanced or metastatic solid tumors. Using 3 + 3 design, patients underwent 14-day treatment cycles with anti-TIGIT antibody etigilimab alone (Phase 1a; 0.3, 1.0, 3.0, 10.0, 20.0 mg/kg intravenously) or in combination with anti-PD-1 antibody nivolumab (Phase 1b; 3.0, 10.0, 20.0 mg/kg etigilimab and 240 mg nivolumab). Primary objective was safety and tolerability. RESULTS: Thirty-three patients were enrolled (Phase 1a, n = 23; Phase 1b, n = 10). There were no dose-limiting toxicities (DLT). MTD for single and combination therapy was not determined; maximum administered dose was 20 mg/kg. The most commonly reported adverse events (AE) were rash (43.5%), nausea (34.8%), and fatigue (30.4%) in Phase 1a and decreased appetite (50.0%), nausea (50.0%), and rash (40%) in Phase 1b. Six patients experienced Grade ≥3 treatment-related AEs. In Phase 1a, 7 patients (30.0%) had stable disease. In Phase 1b, 1 patient had a partial response; 1 patient had prolonged stable disease of nearly 8 months. Median progression-free survival was 56.0 days (Phase 1a) and 57.5 days (Phase 1b). Biomarker correlative analyses demonstrated evidence of clear dose-dependent target engagement by etigilimab. CONCLUSIONS: Etigilimab had an acceptable safety profile with preliminary evidence of clinical benefit alone and in combination with nivolumab and warrants further investigation in clinical trials.
Authors
Mettu, NB; Ulahannan, SV; Bendell, JC; Garrido-Laguna, I; Strickler, JH; Moore, KN; Stagg, R; Kapoun, AM; Faoro, L; Sharma, S
MLA Citation
Mettu, Niharika B., et al. “A Phase 1a/b Open-Label, Dose-Escalation Study of Etigilimab Alone or in Combination with Nivolumab in Patients with Locally Advanced or Metastatic Solid Tumors.Clin Cancer Res, vol. 28, no. 5, Mar. 2022, pp. 882–92. Pubmed, doi:10.1158/1078-0432.CCR-21-2780.
URI
https://scholars.duke.edu/individual/pub1502696
PMID
34844977
Source
pubmed
Published In
Clinical Cancer Research
Volume
28
Published Date
Start Page
882
End Page
892
DOI
10.1158/1078-0432.CCR-21-2780

Cabozantinib with or without Panitumumab for RAS wild-type metastatic colorectal cancer: impact of MET amplification on clinical outcomes and circulating biomarkers.

PURPOSE: Acquired resistance to EGFR inhibitors in metastatic colorectal cancer (mCRC) remains a hurdle for effective treatment. MET amplification has been indicated as a driver of acquired resistance. Clinical activity has been demonstrated for the combination of EGFR and MET inhibitors in mCRC. But the impact of this regimen on angiogenesis and inflammation remains largely unknown. METHODS: In this non-randomized, open-label phase Ib/II study, four patients were treated with cabozantinib alone and 25 patients received the combination of cabozantinib and panitumumab. MET amplification was detected in blood in all four patients treated with cabozantinib monotherapy and 5/25 patients treated with cabozantinib and panitumumab combination therapy. Plasma samples from 28 patients were available for biomarker analysis. RESULTS: A panel of circulating protein biomarkers was assessed in patient plasma at baseline and on-treatment. Baseline marker levels were analyzed for prognostic value for clinical outcomes, including MET amplification as a covariate. HGF and OPN were prognostic for both progression-free survival (PFS) and overall survival (OS), while six markers (IL-6, VCAM-1, VEGF-R1, TSP-2, TIMP-1, ICAM-1) were prognostic only for OS. In patients with MET amplification, baseline PDGF-AA, PDGF-BB, TGF-β1, and VEGF-C levels were significantly higher, whereas baseline TGFβ-R3 levels were significantly lower than MET non-amplified patients. On-treatment change of four markers (CD73, PlGF, PDGF-BB, VEGF) were significantly different between MET amplified and non-amplified subpopulations. CONCLUSION: This study identified circulating HGF and several inflammatory and angiogenic proteins as prognostic biomarkers. Furthermore, MET amplification status is associated with both baseline expression and on-treatment modulation of members of angiogenesis and TGF-β pathway proteins. CLINICAL TRIALS REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT02008383.
Authors
Jia, J; Howard, L; Liu, Y; Starr, MD; Brady, JC; Niedzwiecki, D; Strickler, JH; Nixon, AB
MLA Citation
Jia, Jingquan, et al. “Cabozantinib with or without Panitumumab for RAS wild-type metastatic colorectal cancer: impact of MET amplification on clinical outcomes and circulating biomarkers.Cancer Chemother Pharmacol, vol. 89, no. 3, Mar. 2022, pp. 413–22. Pubmed, doi:10.1007/s00280-022-04404-8.
URI
https://scholars.duke.edu/individual/pub1510611
PMID
35171350
Source
pubmed
Published In
Cancer Chemother Pharmacol
Volume
89
Published Date
Start Page
413
End Page
422
DOI
10.1007/s00280-022-04404-8

Phase 1b/2, open-label, dose-escalation and expansion trial of tucatinib in combination with trastuzumab with and without oxaliplatin-based chemotherapy or pembrolizumab in patients with unresectable or metastatic HER2+ gastrointestinal cancers (trial in

<jats:p> TPS376 </jats:p><jats:p> Background: Human epidermal growth factor receptor 2 ( HER2) gene amplification or protein overexpression (HER2+) occurs in many gastrointestinal (GI) cancers; thus, there is interest in evaluating HER2-targeted therapies in these tumor types. Tucatinib (TUC) is a highly selective HER2-directed tyrosine kinase inhibitor with minimal EGFR inhibition, approved in multiple regions for HER2+ metastatic breast cancer. In patient-derived xenograft models of HER2+ tumors (including esophageal, gastric, and colorectal cancers), TUC + trastuzumab showed superior anti-tumor activity compared with either agent alone (Kulukian 2020). In the MOUNTAINEER study, TUC + trastuzumab in HER2+ metastatic colorectal cancer (CRC) resulted in an objective response rate of 52% and a median duration of response of 10.4 months (interim results, Strickler 2019). The SGNTUC-024 study (NCT04430738) will evaluate TUC + trastuzumab with and without oxaliplatin-based chemotherapy or pembrolizumab in patients with unresectable or metastatic GI cancers. Methods: SGNTUC-024 is an open-label, dose escalation and expansion phase 1b/2 trial. Phase 1b assesses the safety and tolerability of TUC + trastuzumab + either FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) with or without pembrolizumab. One chemotherapy-free cohort is planned (TUC + trastuzumab + pembrolizumab). The initial phase 1b cohort enrolled patients with gastric, esophageal, and gastroesophageal junction (GEJ) adenocarcinomas; cholangiocarcinoma; gallbladder carcinoma; and CRC to receive TUC (150 mg oral [PO] twice daily [BID]) + trastuzumab + FOLFOX. Subsequent phase 1b cohorts will receive TUC (300 mg PO BID) + trastuzumab + either FOLFOX or CAPOX. Once the recommended dose for use with oxaliplatin is identified, cohorts enrolling patients with gastric, esophageal, and GEJ adenocarcinomas will open with patients receiving TUC (300 mg PO BID) + trastuzumab + pembrolizumab with or without either FOLFOX or CAPOX. Phase 2 will expand the assessment of safety and efficacy and enroll 2 cohorts: patients with gastric, esophageal, and GEJ adenocarcinomas (to receive TUC + trastuzumab + pembrolizumab + either FOLFOX or CAPOX, Cohort A) and patients with CRC (to receive TUC + trastuzumab + FOLFOX, Cohort B). Safety and efficacy will be summarized with descriptive statistics. Patients that receive chemotherapy must be eligible for an oxaliplatin-based regimen as standard of care. Patients with irradiated or resected central nervous system (CNS) lesions may enroll, and patients with known active CNS lesions may be eligible for phase 2. The phase 1b portion of the trial is currently enrolling. Clinical trial information: NCT04430738. </jats:p>
Authors
Park, H; Bekaii-Saab, TS; Kim, SS; Kamath, SD; Pishvaian, MJ; Chen, C; Zhen, DB; Mayor, JG; Tan, Q; Strickler, JH
MLA Citation
Park, Haeseong, et al. “Phase 1b/2, open-label, dose-escalation and expansion trial of tucatinib in combination with trastuzumab with and without oxaliplatin-based chemotherapy or pembrolizumab in patients with unresectable or metastatic HER2+ gastrointestinal cancers (trial in progress).Journal of Clinical Oncology, vol. 40, no. 4_suppl, American Society of Clinical Oncology (ASCO), 2022, pp. TPS376–TPS376. Crossref, doi:10.1200/jco.2022.40.4_suppl.tps376.
URI
https://scholars.duke.edu/individual/pub1517958
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
40
Published Date
Start Page
TPS376
End Page
TPS376
DOI
10.1200/jco.2022.40.4_suppl.tps376