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:

A Phase II Clinical Trial of Combination Nivolumab (Opdivo), Ipilimumab (Yervoy), and Taxane in Patients with Untreated Metastatic Non-Small Cell Lung Cancer (NSCLC) (The OPTIMAL Trial)

Administered By
Duke Cancer Institute
Awarded By
Bristol-Myers Squibb Company
Role
Principal Investigator
Start Date
End Date

A Phase 2 Study of Poziotinib in Patients with Non-Small Cell Lung Cancer, Locally Advanced or Metastatic, with EGFR or HER2 Exon 20 Insertion Mutation (POZITIVE20-1)

Administered By
Duke Cancer Institute
Awarded By
Spectrum Pharmaceuticals, Inc
Role
Principal Investigator
Start Date
End Date

A Phase 1 Dose Escalation and Phase 2 Randomized, Open-Label Study of Nivolumab and Veliparib in Combination with Platinum Doublet Chemotherapy in Subjects with Metastatic or Advanced Non-Small Cell Lung Cancer (NSCLC)

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

An open-label Phase I dose-escalation study to evaluate the safety, tolerability, max. tolerated dose, pharmacokinetics,and pharmacodynamics of the anti-C4.4a antibody drug conjugate BAY 1129980 in subjects w/ advanced solid tumors known to expressC4

Administered By
Duke Cancer Institute
Awarded By
Bayer HealthCare AG
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
Awarded By
Adaptimmune Limited
Role
Principal Investigator
Start Date
End Date

Publications:

Veliparib and nivolumab in combination with platinum doublet chemotherapy in patients with metastatic or advanced non-small cell lung cancer: A phase 1 dose escalation study.

OBJECTIVES: Both combinations of the PARP inhibitor veliparib plus platinum doublet chemotherapy (CT), and the programmed death receptor-1 (PD-1) inhibitor nivolumab plus CT have demonstrated encouraging efficacy for treatment of non-small cell lung cancer (NSCLC). This phase 1 dose-escalation study (NCT02944396) evaluated the quadruple combination of veliparib with nivolumab and doublet CT in patients with unresectable advanced/metastatic NSCLC. MATERIALS AND METHODS: Patients were enrolled into five dosing cohorts: patients received veliparib 120 mg twice daily (BID) combined with nivolumab 360 mg, carboplatin AUC 6 mg/mL∙min, and paclitaxel 200 mg/m2 (C/PAC) or veliparib 80/120/200/240 mg BID in combination with nivolumab 360 mg, carboplatin AUC 6 mg/mL∙min, and pemetrexed 500 mg/m2 (C/PEM). Primary objective was to identify the recommended phase 2 dose (RP2D) of veliparib + nivolumab + CT. Safety, tolerability, and efficacy of this combination were also assessed. RESULTS: Twenty-five patients were enrolled: 6 patients received veliparib 120 mg BID + nivolumab + C/PAC and 19 received veliparib (80-240 mg BID) + nivolumab + C/PEM. No dose-limiting toxicities were reported, and the RP2Ds were veliparib 120 mg BID + nivolumab + C/PAC, and veliparib 240 mg BID + nivolumab + C/PEM. The most common any-grade adverse events (AEs) were fatigue (56%), nausea (52%), and anemia (48%). Grade 3/4 AEs included anemia (32%) and neutropenia (24%), and the most frequent serious AE was malignant neoplasm progression (12%). Veliparib exhibited approximately dose proportional kinetics in the dose range 80-240 mg BID combined with nivolumab and C/PEM, with no effects on pemetrexed pharmacokinetics. Overall, the confirmed objective response rate was 40%, and best overall response was 64%. CONCLUSION: Veliparib combined with nivolumab and platinum doublet CT was tolerated in patients with advanced/metastatic NSCLC, and no evidence of drug-drug interaction was observed. Although preliminary, this quadruple therapy may have promising antitumor activity.
Authors
Clarke, JM; Patel, JD; Robert, F; Kio, EA; Thara, E; Ross Camidge, D; Dunbar, M; Nuthalapati, S; Dinh, MH; Bach, BA
MLA Citation
Clarke, Jeffrey M., et al. “Veliparib and nivolumab in combination with platinum doublet chemotherapy in patients with metastatic or advanced non-small cell lung cancer: A phase 1 dose escalation study.Lung Cancer, vol. 161, Nov. 2021, pp. 180–88. Pubmed, doi:10.1016/j.lungcan.2021.09.004.
URI
https://scholars.duke.edu/individual/pub1498511
PMID
34607210
Source
pubmed
Published In
Lung Cancer
Volume
161
Published Date
Start Page
180
End Page
188
DOI
10.1016/j.lungcan.2021.09.004

Immune Checkpoint Inhibitors in the Aged.

PURPOSE OF REVIEW: Large phase III trials have established the benefit of checkpoint blockade across multiple tumor types, but patient representation is limited in some subgroups including the aged population. There are several changes in the immune system that occur with age (termed immunosenescence) that could potentially limit efficacy in aged populations. RECENT FINDINGS: Despite the concerns stated above, available evidence from prospective trials, retrospective cohorts, and registry data suggest that elderly patients achieve similar benefit with immune checkpoint blockade in comparison to the general population and do not have increased toxicity. However, as patients age, they are at higher risk of developing a decline in multiple physiologic systems (including the immune system) and reduced ability to recover from illness. Clinical evidence shows that patients who have a poor performance status have inferior outcomes and limited clinical benefit from checkpoint blockade. Clinicians should take an individualized approach that accounts for each patient's health status rather than considering age alone when determining who should be offered checkpoint blockade therapy.
Authors
Isaacs, J; Antonia, S; Clarke, J
MLA Citation
Isaacs, James, et al. “Immune Checkpoint Inhibitors in the Aged.Curr Oncol Rep, vol. 23, no. 10, Aug. 2021, p. 115. Pubmed, doi:10.1007/s11912-021-01106-x.
URI
https://scholars.duke.edu/individual/pub1492893
PMID
34342733
Source
pubmed
Published In
Current Oncology Reports
Volume
23
Published Date
Start Page
115
DOI
10.1007/s11912-021-01106-x

Pleural effusions associated with squamous cell lung carcinoma have a low diagnostic yield and a poor prognosis.

Background: Malignant pleural effusion (MPE) portends a poor prognosis in non-small cell lung cancer (NSCLC). However, the yield of pleural fluid cytology as well as survival of patients with MPE associated with squamous cell carcinoma versus adenocarcinoma is not well understood. We conducted this study to assess the diagnostic yield of pleural cytology and survival of patients with NSCLC related MPE. Methods: We performed a single-center, retrospective analysis of patients with NSCLC related MPE between 2010 and 2017. Kaplan-Meier method was used to compare survival and Cox proportional hazards analysis to assess if squamous cell cytopathology was associated with mortality. Results: We identified 277 patients, 29 with squamous cell and 248 with adenocarcinoma MPE. Pleural fluid cytology from initial thoracentesis was diagnostic in 13.8% (4/29) patients with squamous cell and 80.2% (199/248) with adenocarcinoma (P<0.001). Cytology from second thoracentesis was diagnostic in 13.3% (2/15) patients with squamous cell carcinoma, compared to 37.5% (12/32) with adenocarcinoma (P=0.17). There was no statistically significant difference in the pleural biopsy yield from medical pleuroscopy or video-assisted thoracoscopic surgery (VATS) in the two groups. The median survival of patients with squamous cell MPE was 112 [interquartile range (IQR): 44-220] days versus 194 (IQR: 54-523) days in adenocarcinoma (Log-rank test P=0.04). Multivariate Cox proportional hazards analysis showed that squamous cell cytopathology was independent predictor of mortality (hazard ratio for death of 1.73, 95% CI: 1.1-2.6; P=0.01). Conclusions: Pleural fluid cytology has a low diagnostic yield in squamous cell carcinoma MPE, and these patients have a poor survival compared to lung adenocarcinoma.
Authors
Dorry, M; Davidson, K; Dash, R; Jug, R; Clarke, JM; Nixon, AB; Mahmood, K
MLA Citation
Dorry, Michael, et al. “Pleural effusions associated with squamous cell lung carcinoma have a low diagnostic yield and a poor prognosis.Transl Lung Cancer Res, vol. 10, no. 6, June 2021, pp. 2500–08. Pubmed, doi:10.21037/tlcr-21-123.
URI
https://scholars.duke.edu/individual/pub1487860
PMID
34295657
Source
pubmed
Published In
Translational Lung Cancer Research
Volume
10
Published Date
Start Page
2500
End Page
2508
DOI
10.21037/tlcr-21-123

Immune Checkpoint Combinations with Inflammatory Pathway Modulators

Immune checkpoint inhibition of program death protein-1 (PD-1) and its ligands PD-L1 and PD-L2 is an established therapeutic modality in melanoma, non-small cell lung cancer, renal cell carcinoma, and other tumor types. Unfortunately, 60 to 80% of all patients experience disease progression and become refractory to immune checkpoint therapies. Broadly, mechanisms of immune checkpoint inhibitor resistance can be categorized as presence of oncogenic driver mutations, severe T cell exhaustion, neoantigen burden, epigenetic alterations, or mutations involved in critical pathways including PTEN, JAK, or Wnt signaling. The dysregulation of inflammatory signaling pathways (namely, genes involved in angiogenesis, chemotaxis, matrix remodeling, wound healing, and mesenchymal transition) is of critical importance to response to immune checkpoint therapies. Inflammatory cytokine signaling pathways exert downstream effects on immunosuppressive elements such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) which inhibit the function of effector T cells, NK cells, and dendritic cells, promoting immune tolerance and tumor growth. We herein review three targets for inflammatory pathway modulation: indoleamine 2,3-dioxygenase (IDO), transforming growth factor β (TGFβ), and adenosine. Targeting these pathways may address the unmet need to develop novel therapeutic approaches to increase response rates to immune checkpoint inhibitors and improve clinical outcomes.
MLA Citation
DeVito, N., et al. “Immune Checkpoint Combinations with Inflammatory Pathway Modulators.” Current Cancer Research, 2018, pp. 219–41. Scopus, doi:10.1007/978-3-319-63757-0_8.
URI
https://scholars.duke.edu/individual/pub1494214
Source
scopus
Published Date
Start Page
219
End Page
241
DOI
10.1007/978-3-319-63757-0_8

Predictive Value of Combining Biomarkers for Clinical Outcomes in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors.

INTRODUCTION: A high tumor mutational burden (TMB) (≥10 mut/Mb) has been associated with improved clinical benefit in non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI) and is a tumor agnostic indication for pembrolizumab across tumor types. We explored whether combining TMB with programmed cell death ligand 1 (PD-L1) and pretreatment neutrophil-lymphocyte ratio (NLR) was associated with improved outcomes in ICI-treated NSCLC. METHODS: We retrospectively analyzed patients treated with ICI with Foundation One genomic testing, including TMB. Optimal cutoff for prediction of response by TMB was determined by receiver operating characteristic analysis, and area under the curve (AUC) was calculated for all 3 biomarkers and combinations. Cox model was used to assess prognostic factors of overall survival (OS) and time to progression (TTP). Survival cutoffs calculated with Kaplan-Meier survival curves were TMB ≥10 mut/Mb, PD-L1 ≥50%, NLR <5, and combined biomarkers. RESULTS: Data from 88 patients treated were analyzed. The optimal TMB cutoff was 9.24 mut/Mb (AUC, 0.62), improving to 0.74 combining all 3 biomarkers. Adjusted Cox model showed that TMB ≥10 mut/Mb was an independent factor of OS (hazard ratio [HR], 0.31; 95% confidence interval; 0.14-0.69; P = .004) and TTP (HR, 0.46; 95% CI, 0.27-0.77; P = .003). The combination of high TMB with positive PD-L1 and low NLR was significantly associated with OS (P = .038) but not TTP. CONCLUSIONS: TMB has modest predictive and prognostic power for clinical outcomes after ICI treatment. The combination of TMB, PD-L1, and NLR status improves this power.
Authors
Kao, C; Powers, E; Wu, Y; Datto, MB; Green, MF; Strickler, JH; Ready, NE; Zhang, T; Clarke, JM
MLA Citation
URI
https://scholars.duke.edu/individual/pub1481799
PMID
33972172
Source
pubmed
Published In
Clin Lung Cancer
Published Date
DOI
10.1016/j.cllc.2021.03.017