Jeffrey Clarke

Positions:

Assistant Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2008

Indiana University School of Medicine

Categorical Internal Medicine Residency, Medicine

Duke University School of Medicine

Hematology and Medical Oncology Fellowship, Medicine

Duke University School of Medicine

Internal Medicine Chief Resident, Medicine

Duke University School of Medicine

Grants:

TOP 1705

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

SPI-POZ-202

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

M15-534

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

Bayer 16044

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

A screening protocol to determine tumor antigen expression and HLA sub-type ofr eligibility determination for clinical trials evaluating the safety and efficacy of Autologous T Cell expressing enhance

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

Publications:

Use of low-frequency driver mutations detected by cell-free circulating tumor DNA to guide targeted therapy in non-small-cell lung cancer: A multicenter case series

© 2019 American Society of Clinical Oncology. Purpose To evaluate the clinical outcome of patients with non-small-cell lung cancer treated by targeting low variant allelic frequency (VAF) driver mutations identified through cell-free DNA (cfDNA) next-generation sequencing (NGS). Detection of driver mutations in cancer is critically important in the age of targeted therapy, where both tumor-based as well as cfDNA sequencing methods have been used for therapeutic decision making. We hypothesized that VAF should not be predictive of response and that low VAF alterations detected by cfDNA NGS can respond to targeted therapy. Patients and Methods A multicenter retrospective case review was performed to identify patients with non-small-cell lung cancer who received targeted molecular therapy on the basis of findings of low VAF alterations in cfDNA NGS. Mutations at low VAF were defined as < 0.2% mutated cfDNA molecules in a background of wild-type cfDNA. Results One hundred seventy-two patients underwent cfDNA NGS testing. Of the 172 patients, 12 were identified as having low VAF driver alterations and were considered for targeted therapy. The median progression-free survival (PFS) for all patients was 52 weeks (range, 17 to 88 weeks). For patients with EGFR exon 19 deletion (n = 7), the median PFS was 52 weeks (range, 17 to 60.5 weeks). For patients with EML4-ALK fusions (n = 3), the median PFS was 60 weeks (range, 18 to 88 weeks). The median overall survival for all patients after diagnosis was 57.6 weeks. Conclusion Targeted treatment response for driver mutations detected by cfDNA may be independent of VAF, even in relation to other higher VAF aberrations in plasma, and directly dependent on the underlying disease biology and ability to treat the patient with appropriate targeted therapy.
Authors
Jacobs, MT; Mohindra, NA; Shantzer, L; Chen, IL; Phull, H; Mitchell, W; Raymond, VM; Banks, KC; Nagy, RJ; Lanman, RB; Christensen, J; Patel, JD; Clarke, J; Patel, SP
MLA Citation
URI
https://scholars.duke.edu/individual/pub1428069
Source
scopus
Published In
Jco Precision Oncology
Volume
2
Published Date
DOI
10.1200/PO.17.00318

EBUS-FNA cytologic-histologic correlation of PD-L1 immunohistochemistry in non-small cell lung cancer.

INTRODUCTION: Immune checkpoint pathway markers induce immune tolerance to non-small cell lung cancer (NSCLC). Therapeutic antibodies targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway have demonstrated efficacy in tumors expressing relatively high PD-L1 levels. Minimally invasive endobronchial ultrasound-guided fine needle aspiration allows patients with inoperable tumors or comorbidities to attain a confirmatory diagnosis. The aims of the present study were to determine whether PD-L1 testing is equivalent to cytology and biopsy or resection specimens at different tumor proportion score cutoffs and for different NSCLC subtypes. MATERIALS AND METHODS: Data were retrospectively collected for patients with paired NSCLC cytology and surgical resection specimens from May 4, 2007 to May 4, 2017. The Food and Drug Administration-approved Dako PD-L1 immunohistochemistry 22C3 pharmDx kit was used to measure PD-L1 on paired cytology cell block and biopsy or resection specimens, and the PD-L1 tumor proportion scores were recorded. Statistical analysis of categorical and continuous variables was performed using SAS, version 9.4. RESULTS: A total of 53 paired cytology and resection samples (27 adenocarcinoma, 25 squamous cell carcinoma, and 1 unclassified) were analyzed. Supposing the resection specimen to reflect the true PD-L1 expression, the sensitivity, specificity, positive predictive value, negative predictive value, and overall agreement for the cytology method was 73.3%, 65.2%, 73.3%, 65.2%, and 69.8%, respectively. For high PD-L1 expression (≥50%), the cytology method demonstrated an overall agreement of 79.2%. The overall agreement between methods was 81.5% and 76% for cases of adenocarcinoma and squamous cell carcinoma, respectively. CONCLUSIONS: NSCLC cytology samples from endobronchial ultrasound-guided fine needle aspiration are suitable for PD-L1 testing, especially using a high PD-L1 expression cutoff of ≥50% and for adenocarcinoma.
Authors
Jug, R; Giovacchini, CX; Liu, B; Green, CL; Clarke, JM; Mahmood, K; Pavlisko, EN
MLA Citation
Jug, Rachel, et al. “EBUS-FNA cytologic-histologic correlation of PD-L1 immunohistochemistry in non-small cell lung cancer.J Am Soc Cytopathol, Apr. 2020. Pubmed, doi:10.1016/j.jasc.2020.04.003.
URI
https://scholars.duke.edu/individual/pub1438217
PMID
32336671
Source
pubmed
Published In
J Am Soc Cytopathol
Published Date
DOI
10.1016/j.jasc.2020.04.003

Current multidisciplinary management of brain metastases.

Brain metastasis (BM), the most common adult brain tumor, develops in 20% to 40% of patients with late-stage cancer and traditionally are associated with a poor prognosis. The management of patients with BM has become increasingly complex because of new and emerging systemic therapies and advancements in radiation oncology and neurosurgery. Current therapies include stereotactic radiosurgery, whole-brain radiation therapy, surgical resection, laser-interstitial thermal therapy, systemic cytotoxic chemotherapy, targeted agents, and immune-checkpoint inhibitors. Determining the optimal treatment for a specific patient has become increasingly individualized, emphasizing the need for multidisciplinary discussions of patients with BM. Recognizing and addressing the sequelae of BMs and their treatment while maintaining quality of life and neurocognition is especially important because survival for patients with BMs has improved. The authors present current and emerging treatment options for patients with BM and suggest approaches for managing sequelae and disease recurrence.
Authors
MLA Citation
Moravan, Michael J., et al. “Current multidisciplinary management of brain metastases.Cancer, vol. 126, no. 7, Apr. 2020, pp. 1390–406. Pubmed, doi:10.1002/cncr.32714.
URI
https://scholars.duke.edu/individual/pub1428070
PMID
31971613
Source
pubmed
Published In
Cancer
Volume
126
Published Date
Start Page
1390
End Page
1406
DOI
10.1002/cncr.32714

Definitive Radiotherapy for Inoperable Stage IIB Non-small-cell Lung Cancer: Patterns of Care and Comparative Effectiveness.

BACKGROUND: The purpose of this study was to analyze practice patterns and perform comparative effectiveness of definitive radiotherapy techniques for inoperable stage IIB (American Joint Committee on Cancer eighth edition) non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Adults in the National Cancer Database diagnosed with T3N0M0 or T1-2N1M0 NCSLC between 2004 and 2015 who received definitive radiotherapy were identified. Cases were divided as stereotactic body radiotherapy (SBRT), hypofractionated radiotherapy (HFRT), or conventionally fractionated radiotherapy (CFRT) and stratified by systemic therapy (ST). Cox proportional hazards models evaluated the effect of covariates on overall survival (OS). Subgroup analysis by tumor size, chest wall invasion, multifocality, and ST use was performed with Kaplan-Meier estimates of OS. RESULTS: A total of 10,081 subjects met inclusion criteria: 4401 T3N0M0 (66.5% CFRT, 11.0% HFRT, and 22.5% SBRT) and 5680 T1-2N1M0 (92.5% CFRT and 7.5% HFRT). For T3N0M0 NSCLC, SBRT utilization increased from 3.7% in 2006% to 35.4% in 2015. Subjects treated with SBRT were more likely to have smaller tumors, multifocal tumors, or adenocarcinoma histology. SBRT resulted in similar or superior OS compared with CFRT for tumors > 5 cm, tumors invading the chest wall, or multifocal tumors. SBRT was significantly associated with improved OS on multivariate analysis (hazard ratio, 0.715; P < .001). For T1-2N1M0 NSCLC, patients treated with HFRT were significantly older and less likely to receive ST; nevertheless, there was no difference in OS between HFRT and CFRT on multivariate analysis. CONCLUSION: CFRT + ST is utilized most frequently to treat stage IIB NSCLC in the United States when surgery is not performed, though it is decreasing. SBRT utilization for T3N0M0 NSCLC is increasing and was associated with improved OS.
Authors
Jacobs, CD; Gao, J; Wang, X; Clarke, JM; Tong, B; Ready, NE; Suneja, G; Kelsey, CR; Torok, JA
MLA Citation
Jacobs, Corbin D., et al. “Definitive Radiotherapy for Inoperable Stage IIB Non-small-cell Lung Cancer: Patterns of Care and Comparative Effectiveness.Clin Lung Cancer, vol. 21, no. 3, May 2020, pp. 238–46. Pubmed, doi:10.1016/j.cllc.2019.10.005.
URI
https://scholars.duke.edu/individual/pub1422411
PMID
31757764
Source
pubmed
Published In
Clin Lung Cancer
Volume
21
Published Date
Start Page
238
End Page
246
DOI
10.1016/j.cllc.2019.10.005

Population pharmacokinetics of vactosertib, a new TGF-β receptor type Ι inhibitor, in patients with advanced solid tumors.

PURPOSE: Vactosertib, a novel inhibitor of transforming growth factor-β type Ι receptor, is under development for the treatment of various cancers. The objective of this study was to characterize the population pharmacokinetics of vactosertib in patients with solid tumors. METHODS: Vactosertib population pharmacokinetics was assessed by nonlinear mixed-effects modelling of plasma concentration-time data obtained from a first-in-human phase 1 trial conducted in patients with advanced solid tumors. The final population pharmacokinetic model was constructed by assessing the effect of covariates on pharmacokinetic parameters including demographic characteristics, laboratory values, hepatic and renal function, and concomitant medications. The robustness of the final model was evaluated using a bootstrap method as well as visual predictive check based on Monte Carlo simulations and goodness-of-fit plots. RESULTS: A total of 559 concentrations from 29 patients were available for pharmacokinetic analysis. A two-compartment linear model with first-order absorption and absorption lag time adequately described the population pharmacokinetics of vactosertib. The estimates of apparent clearance (CL/F) and volume of central compartment (Vc/F) were 31.9 L/h (inter-individual variability, 0.481) and 82.9 L (inter-individual variability, 0.534), respectively. The mixture model accounts for both typical absorption profile in the majority of patients and distinct profile in some patients with uncommon gastrointestinal conditions. Body mass index was significantly associated with Vc/F. CONCLUSIONS: The model developed in this study adequately describes the population pharmacokinetics of vactosertib in patients with advanced solid tumors. The pharmacokinetic characteristics assessed using the model would provide useful quantitative information to assist the future clinical development of vactosertib.
Authors
Jung, SY; Yug, JS; Clarke, JM; Bauer, TM; Keedy, VL; Hwang, S; Kim, S-J; Chung, EK; Lee, JI
MLA Citation
Jung, Su Young, et al. “Population pharmacokinetics of vactosertib, a new TGF-β receptor type Ι inhibitor, in patients with advanced solid tumors.Cancer Chemother Pharmacol, vol. 85, no. 1, Jan. 2020, pp. 173–83. Pubmed, doi:10.1007/s00280-019-03979-z.
URI
https://scholars.duke.edu/individual/pub1418400
PMID
31673825
Source
pubmed
Published In
Cancer Chemother Pharmacol
Volume
85
Published Date
Start Page
173
End Page
183
DOI
10.1007/s00280-019-03979-z