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:

Phase I Study of 2- or 3-Week Dosing of Telisotuzumab Vedotin, an Antibody-Drug Conjugate Targeting c-Met, Monotherapy in Patients with Advanced Non-Small Cell Lung Carcinoma.

PURPOSE: Telisotuzumab vedotin (Teliso-V) is an anti-c-Met-directed antibody-drug conjugate. Here, we present safety and efficacy data from a phase I/Ib study of Teliso-V monotherapy evaluated in once every 2 weeks/once every 3 weeks schedules in patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: During dose escalation, patients received Teliso-V monotherapy intravenously once every 3 weeks (0.15-3.3 mg/kg) or once every 2 weeks (1.6-2.2 mg/kg). The dose-expansion phase enrolled patients with NSCLC and c-Met H-score ≥150 (c-Met+) or MET amplification/exon 14 skipping mutations. Safety, pharmacokinetics, and efficacy were assessed. Herein, the analysis of patients receiving ≥1.6 mg/kg once every 2 weeks or ≥2.4 mg/kg once every 3 weeks Teliso-V is reported. RESULTS: Fifty-two patients with NSCLC were enrolled and received ≥1.6 mg/kg Teliso-V once every 2 weeks (n = 28) or ≥2.4 mg/kg Teliso-V once every 3 weeks (n = 24). The most common adverse events were fatigue (54%), peripheral neuropathy (42%), and nausea (38%). No dose-limiting toxicities were observed for Teliso-V once every 2 weeks and once every 3 weeks up to 2.2 and 2.7 mg/kg, respectively. The recommended phase II dose was established at 1.9 mg/kg once every 2 weeks and 2.7 mg/kg once every 3 weeks on the basis of overall safety and pharmacokinetics. Forty of 52 patients were c-Met+ (33 nonsquamous, 6 squamous, 1 mixed histology) and were included in the efficacy-evaluable population. Of those, 9 (23%) had objective responses with median duration of response of 8.7 months; median progression-free survival was 5.2 months. CONCLUSIONS: Teliso-V monotherapy was tolerated and showed antitumor activity in c-Met+ NSCLC. On the basis of overall safety, pharmacokinetics, and efficacy outcomes, 1.9 mg/kg Teliso-V once every 2 weeks and 2.7 mg/kg once every 3 weeks schedules were selected for further clinical development.
Authors
Camidge, DR; Morgensztern, D; Heist, RS; Barve, M; Vokes, E; Goldman, JW; Hong, DS; Bauer, TM; Strickler, JH; Angevin, E; Motwani, M; Parikh, A; Sun, Z; Bach, BA; Wu, J; Komarnitsky, PB; Kelly, K
MLA Citation
Camidge, D. Ross, et al. “Phase I Study of 2- or 3-Week Dosing of Telisotuzumab Vedotin, an Antibody-Drug Conjugate Targeting c-Met, Monotherapy in Patients with Advanced Non-Small Cell Lung Carcinoma.Clin Cancer Res, vol. 27, no. 21, Nov. 2021, pp. 5781–92. Pubmed, doi:10.1158/1078-0432.CCR-21-0765.
URI
https://scholars.duke.edu/individual/pub1494545
PMID
34426443
Source
pubmed
Published In
Clinical Cancer Research
Volume
27
Published Date
Start Page
5781
End Page
5792
DOI
10.1158/1078-0432.CCR-21-0765

Safety, Efficacy, and Biomarker Results from a Phase Ib Study of the Anti-DKK1 Antibody DKN-01 in Combination with Pembrolizumab in Advanced Esophagogastric Cancers.

Therapeutic combinations targeting innate and adaptive immunity and predictive biomarkers of response in esophagogastric cancer (EGC) are needed. We assessed safety and clinical utility of DKN-01 (a novel DKK1-neutralizing IgG4 antibody) combined with pembrolizumab and retrospectively determined DKK1 tumoral expression as a biomarker. Patients with advanced EGC received intravenous DKN-01 (150 or 300 mg) on days 1 and 15 with pembrolizumab 200 mg on day 1 in 21-day cycles. Clinical response was assessed by RECIST v1.1. Association of tumoral DKK1 mRNA expression (H-score: high ≥ upper-tertile, low < upper-tertile) with response was assessed with PD-L1 levels as a covariate. Sixty-three patients received DKN-01 150 mg (n = 2) or 300 mg (n = 61) plus pembrolizumab. Common adverse events were fatigue, anemia, blood alkaline phosphatase elevation, aspartate aminotransferase elevation, and hyponatremia. Among evaluable anti-PD-1/PD-L1-naïve patients receiving DKN-01 300 mg and pembrolizumab, objective response rate (ORR) was 11.4% (5/44) and 18.5% (5/27) in patients with gastroesophageal junction or gastric cancer (GEJ/GC). Among response-evaluable anti-PD-1/PD-L1-naïve patients with GEJ/GC and known tumoral DKK1 expression, ORR was 50% in DKK1-high and 0% in DKK1-low patients, median PFS was 22.1 vs. 5.9 weeks (HR, 0.24; 95% CI, 0.08-0.67), respectively, and median OS was 31.6 weeks vs. 17.4 weeks (HR, 0.41; 95% CI, 0.16-1.07), respectively. Association of DKK1 expression with PFS was independent of PD-L1 expression (adjusted HR, 0.21; 95% CI, 0.06-0.69). DKN-01 combined with pembrolizumab was well tolerated with no new safety signals. Antitumor activity was enriched in anti-PD-1/PD-L1-naïve patients with GEJ/GC whose tumors expressed high DKK1.
Authors
Klempner, SJ; Bendell, JC; Villaflor, VM; Tenner, LL; Stein, SM; Rottman, JB; Naik, GS; Sirard, CA; Kagey, MH; Chaney, MF; Strickler, JH
MLA Citation
Klempner, Samuel J., et al. “Safety, Efficacy, and Biomarker Results from a Phase Ib Study of the Anti-DKK1 Antibody DKN-01 in Combination with Pembrolizumab in Advanced Esophagogastric Cancers.Mol Cancer Ther, vol. 20, no. 11, Nov. 2021, pp. 2240–49. Pubmed, doi:10.1158/1535-7163.MCT-21-0273.
URI
https://scholars.duke.edu/individual/pub1496567
PMID
34482288
Source
pubmed
Published In
Mol Cancer Ther
Volume
20
Published Date
Start Page
2240
End Page
2249
DOI
10.1158/1535-7163.MCT-21-0273

Addressing Resistance to Targeted Therapies in Metastatic Colorectal Cancer.

Metastatic colorectal cancer (mCRC) is the second most common cause of cancer-related death worldwide. In the mid-1980s, the median overall survival (OS) for patients with mCRC ranged from 10 to 12 months from the time of initial diagnosis. In more recent studies, this median has more than doubled and is commonly reported at more than 25 to 30 months. These improvements are due, in large part, to the introduction of multiple novel agents during the last 3 decades. Despite these improvements, however, nearly all patients treated with palliative chemotherapy will eventually develop resistance and ultimately succumb to progression of metastatic disease. Understanding the mechanisms by which malignant cells evade treatment could unlock novel therapeutic strategies that overcome resistance and improve survival. In this review, we will discuss some of the drivers of therapeutic resistance in patients with mCRC and present some novel strategies to overcome resistance.
Authors
Jones, J; Ciombor, K; Wu, C; Bekaii-Saab, T; Strickler, J
MLA Citation
Jones, Jeremy, et al. “Addressing Resistance to Targeted Therapies in Metastatic Colorectal Cancer.Oncology (Williston Park), vol. 35, no. 10, Oct. 2021, pp. 654–60. Pubmed, doi:10.46883/ONC.2021.3510.0654.
URI
https://scholars.duke.edu/individual/pub1499303
PMID
34677922
Source
pubmed
Published In
Oncology (Williston Park, N.Y.)
Volume
35
Published Date
Start Page
654
End Page
660
DOI
10.46883/ONC.2021.3510.0654

Phase I Open-Label Study Evaluating the Safety, Pharmacokinetics, and Preliminary Efficacy of Dilpacimab in Patients with Advanced Solid Tumors.

Dilpacimab (formerly ABT-165), a novel dual-variable domain immunoglobulin, targets both delta-like ligand 4 (DLL4) and VEGF pathways. Here, we present safety, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy data from a phase I study (trial registration ID: NCT01946074) of dilpacimab in patients with advanced solid tumors. Eligible patients (≥18 years) received dilpacimab intravenously on days 1 and 15 in 28-day cycles at escalating dose levels (range, 1.25-7.5 mg/kg) until progressive disease or unacceptable toxicity. As of August 2018, 55 patients with solid tumors were enrolled in the dilpacimab monotherapy dose-escalation and dose-expansion cohorts. The most common treatment-related adverse events (TRAE) included hypertension (60.0%), headache (30.9%), and fatigue (21.8%). A TRAE of special interest was gastrointestinal perforation, occurring in 2 patients (3.6%; 1 with ovarian and 1 with prostate cancer) and resulting in 1 death. The PK of dilpacimab showed a half-life ranging from 4.9 to 9.5 days, and biomarker analysis demonstrated that the drug bound to both VEGF and DLL4 targets. The recommended phase II dose for dilpacimab monotherapy was established as 3.75 mg/kg, primarily on the basis of tolerability through multiple cycles. A partial response was achieved in 10.9% of patients (including 4 of 16 patients with ovarian cancer). The remaining patients had either stable disease (52.7%), progressive disease (23.6%), or were deemed unevaluable (12.7%). These results demonstrate that dilpacimab monotherapy has an acceptable safety profile, with clinical activity observed in patients with advanced solid tumors.
Authors
Gordon, MS; Nemunaitis, J; Barve, M; Wainberg, ZA; Hamilton, EP; Ramanathan, RK; Sledge, GW; Yue, H; Morgan-Lappe, SE; Blaney, M; Kasichayanula, S; Motwani, M; Wang, L; Naumovski, L; Strickler, JH
MLA Citation
Gordon, Michael S., et al. “Phase I Open-Label Study Evaluating the Safety, Pharmacokinetics, and Preliminary Efficacy of Dilpacimab in Patients with Advanced Solid Tumors.Mol Cancer Ther, vol. 20, no. 10, Oct. 2021, pp. 1988–95. Pubmed, doi:10.1158/1535-7163.MCT-20-0985.
URI
https://scholars.duke.edu/individual/pub1493267
PMID
34315767
Source
pubmed
Published In
Mol Cancer Ther
Volume
20
Published Date
Start Page
1988
End Page
1995
DOI
10.1158/1535-7163.MCT-20-0985

The Current Molecular Treatment Landscape of Advanced Colorectal Cancer and Need for the COLOMATE Platform.

Authors
Ciombor, K; Jones, J; Strickler, J; Bekaii-Saab, T; Wu, C
MLA Citation
Ciombor, Kristen, et al. “The Current Molecular Treatment Landscape of Advanced Colorectal Cancer and Need for the COLOMATE Platform.Oncology (Williston Park), vol. 35, no. 9, Sept. 2021, pp. 553–59. Pubmed, doi:10.46883/ONC.2021.3509.0553.
URI
https://scholars.duke.edu/individual/pub1497306
PMID
34524770
Source
pubmed
Published In
Oncology (Williston Park, N.Y.)
Volume
35
Published Date
Start Page
553
End Page
559
DOI
10.46883/ONC.2021.3509.0553