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:

A Phase 2 Clinical Trial of Combination Nivolumab, Ipilimumab, and Paclitaxel in Patients With Untreated Metastatic NSCLC: The OPTIMAL Trial.

Introduction: Most patients with advanced NSCLC will experience disease progression and death within 2 years. Novel approaches are needed to improve outcomes. Methods: We conducted an open-label, nonrandomized, phase 2 trial in patients with treatment-naive, advanced NSCLC to assess the safety and efficacy of nivolumab 360 mg every 3 weeks, ipilimumab 1 mg/kg every 6 weeks, and four to six cycles of paclitaxel 80 mg/m2 on days 1 and 8 of every 21-day treatment. The primary end point of the study was median progression-free survival (PFS), with secondary end points of safety, objective response rate, and median overall survival (OS). Results: A total of 46 patients underwent consent and received treatment. The median age was 66 (range: 48-82) years, most had adenocarcinoma (63%), and 50% (23) had programmed death-ligand 1 greater than or equal to 1%. The median follow-up on the study as of October 2021 was 19 months. The primary end point of median PFS was 9.4 months (95% confidence interval [CI]: 5.9-16.6) in all patients regardless of programmed death-ligand 1 expression. The objective response rate for patients in the study was 47.8% (95% CI: 33.4-62.3). The 12-month OS rate was 69.5% (95% CI: 53%-81%), and median OS was not yet reached. Treatment-related grade greater than or equal to 3 adverse events was found in 54.3% of the patients. Conclusions: The toxicity observed was consistent with other reported chemo-immunotherapeutic combinations and was manageable. The primary end point of exceeding median PFS of 9 months was achieved with nivolumab, ipilimumab, and weekly paclitaxel and should be evaluated further in a randomized trial.
MLA Citation
Clarke, Jeffrey M., et al. “A Phase 2 Clinical Trial of Combination Nivolumab, Ipilimumab, and Paclitaxel in Patients With Untreated Metastatic NSCLC: The OPTIMAL Trial.Jto Clin Res Rep, vol. 3, no. 6, June 2022, p. 100337. Pubmed, doi:10.1016/j.jtocrr.2022.100337.
URI
https://scholars.duke.edu/individual/pub1524906
PMID
35719867
Source
pubmed
Published In
Jto Clinical and Research Reports
Volume
3
Published Date
Start Page
100337
DOI
10.1016/j.jtocrr.2022.100337

Poziotinib in Non-Small-Cell Lung Cancer Harboring HER2 Exon 20 Insertion Mutations After Prior Therapies: ZENITH20-2 Trial.

PURPOSE: Insertion mutations in Erb-b2 receptor tyrosine kinase 2 gene (ERBB2 or HER2) exon 20 occur in 2%-5% of non-small-cell lung cancers (NSCLCs) and function as an oncogenic driver. Poziotinib, a tyrosine kinase inhibitor, was evaluated in previously treated patients with NSCLC with HER2 exon 20 insertions. METHODS: ZENITH20, a multicenter, multicohort, open-label phase II study, evaluated poziotinib in patients with advanced or metastatic NSCLC. In cohort 2, patients received poziotinib (16 mg) once daily. The primary end point was objective response rate evaluated by independent review committee (RECIST v1.1); secondary outcome measures were disease control rate, duration of response, progression-free survival, and safety and tolerability. Quality of life was assessed. RESULTS: Between October 2017 and March 2021, 90 patients with a median of two prior lines of therapy (range, 1-6) were treated. With a median follow-up of 9.0 months, objective response rate was 27.8% (95% CI, 18.9 to 38.2); 25 of 90 patients achieved a partial response. Disease control rate was 70.0% (95% CI, 59.4 to 79.2). Most patients (74%) had tumor reduction (median reduction 22%). Median progression-free survival was 5.5 months (95% CI, 3.9 to 5.8); median duration of response was 5.1 months (95% CI, 4.2 to 5.5). Clinical benefit was seen regardless of lines and types of prior therapy, presence of central nervous system metastasis, and types of HER2 mutations. Grade 3 or higher treatment-related adverse events included rash (48.9%), diarrhea (25.6%), and stomatitis (24.4%). Most patients had poziotinib dose reductions (76.7%), with median relative dose intensity of 71.5%. Permanent treatment discontinuation because of treatment-related adverse events occurred in 13.3% of patients. CONCLUSION: Poziotinib demonstrates antitumor activity in previously treated patients with HER2 exon 20 insertion NSCLC.
Authors
Le, X; Cornelissen, R; Garassino, M; Clarke, JM; Tchekmedyian, N; Goldman, JW; Leu, S-Y; Bhat, G; Lebel, F; Heymach, JV; Socinski, MA
MLA Citation
Le, Xiuning, et al. “Poziotinib in Non-Small-Cell Lung Cancer Harboring HER2 Exon 20 Insertion Mutations After Prior Therapies: ZENITH20-2 Trial.J Clin Oncol, vol. 40, no. 7, Mar. 2022, pp. 710–18. Pubmed, doi:10.1200/JCO.21.01323.
URI
https://scholars.duke.edu/individual/pub1502990
PMID
34843401
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
40
Published Date
Start Page
710
End Page
718
DOI
10.1200/JCO.21.01323

Racial Differences in Survival Among Advanced-stage Non-small-Cell Lung Cancer Patients Who Received Immunotherapy: An Analysis of the US National Cancer Database (NCDB).

Lung cancer is the most common cause of cancer death among men and women in the United States, with significant racial disparities in survival. It is unclear whether these disparities persist upon equal utilization of immunotherapy. The purpose of this study was to evaluate the association between race and all-cause mortality among non-small-cell lung cancer (NSCLC) patients who received immunotherapy. We obtained data from the 2016 National Cancer Database on patients diagnosed with advanced-stage (III-IV) NSCLC from 2015 to 2016. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) by race/ethnicity. A total of 2940 patients were included. Non-Hispanic (NH)-Black patients had a lower risk of death relative to NH-White patients (HR: 0.85; 95% CI: 0.73, 0.98) after adjusting for sociodemographic, clinical, and treatment factors. Formal tests of interaction evaluating race with Charlson-Deyo comorbidity score and race with area-level median income were nonsignificant. However, in stratified analyses, NH-Black versus NH-White patients had a lower risk of death in models adjusted for sociodemographic factors among those with at least 1 comorbidity (HR: 0.75; 95% CI: 0.57, 0.97), and those living in regions within the 2 lowest quartiles of median income (HR: 0.82; 95% CI: 0.68, 0.99). Among advanced-stage NSCLC patients who received immunotherapy, NH-Black patients experienced higher survival compared with NH-White patients. We urge the implementation of policies and interventions that seek to equalize access to care as a means of addressing differences in overall NSCLC survival by race.
Authors
Gupta, A; Zhang, D; Braithwaite, D; Karanth, SD; Tailor, TD; Clarke, JM; Akinyemiju, T
MLA Citation
Gupta, Anjali, et al. “Racial Differences in Survival Among Advanced-stage Non-small-Cell Lung Cancer Patients Who Received Immunotherapy: An Analysis of the US National Cancer Database (NCDB).J Immunother, vol. 45, no. 2, Feb. 2022, pp. 132–37. Pubmed, doi:10.1097/CJI.0000000000000400.
URI
https://scholars.duke.edu/individual/pub1500610
PMID
34747372
Source
pubmed
Published In
J Immunother
Volume
45
Published Date
Start Page
132
End Page
137
DOI
10.1097/CJI.0000000000000400

Phase I/IIa Trial of BMS-986148, an Anti-mesothelin Antibody-drug Conjugate, Alone or in Combination with Nivolumab in Patients with Advanced Solid Tumors.

PURPOSE: To assess the safety and tolerability of BMS-986148, a mesothelin-directed antibody-drug conjugate (ADC) ± nivolumab, in patients with selected tumors. PATIENTS AND METHODS: In an international phase I/IIa study [NCT02341625 (CA008-002)], patients received BMS-986148 monotherapy (0.1-1.6 mg/kg intravenously (i.v.) every 3 weeks or 0.4 or 0.6 mg/kg i.v. once weekly; n = 96) or BMS-986148 0.8 mg/kg + nivolumab 360 mg i.v. every 3 weeks (n = 30). The primary endpoint was safety and tolerability. RESULTS: In CA008-002, the most common (≥ 10%) treatment-related adverse events (TRAEs) included increased aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Grade 3/4 TRAEs occurred in 42 patients (49%) receiving BMS-986148 every 3 weeks monotherapy, three (25%) receiving BMS-986148 once-weekly monotherapy, and 10 (33%) receiving BMS-986148 + nivolumab every 3 weeks. Overall, 17 of 126 patients (13%) discontinued because of a TRAE. The MTD of BMS-986148 was 1.2 mg/kg i.v. every 3 weeks. The safety profile of BMS-986148 + nivolumab was similar to that of BMS-986148 monotherapy (0.8 mg/kg). Active ADC exposures increased in a dose-proportional manner with both dosing regimens (every 3 weeks and once weekly). Preliminary clinical activity was observed with BMS-986148 ± nivolumab. No association between mesothelin expression and response was detected. CONCLUSIONS: BMS-986148 ± nivolumab demonstrated a clinically manageable safety profile and preliminary evidence of clinical activity, supporting additional studies combining directed cytotoxic therapies with checkpoint inhibitors as potential multimodal therapeutic strategies in patients with advanced solid tumors.
Authors
Rottey, S; Clarke, J; Aung, K; Machiels, J-P; Markman, B; Heinhuis, KM; Millward, M; Lolkema, M; Patel, SP; de Souza, P; Duca, M; Curigliano, G; Santoro, A; Koyama, T; Brown, M; Vezina, H; He, C; Chu, QS-C
MLA Citation
Rottey, Sylvie, et al. “Phase I/IIa Trial of BMS-986148, an Anti-mesothelin Antibody-drug Conjugate, Alone or in Combination with Nivolumab in Patients with Advanced Solid Tumors.Clin Cancer Res, vol. 28, no. 1, Jan. 2022, pp. 95–105. Pubmed, doi:10.1158/1078-0432.CCR-21-1181.
URI
https://scholars.duke.edu/individual/pub1498440
PMID
34615718
Source
pubmed
Published In
Clinical Cancer Research
Volume
28
Published Date
Start Page
95
End Page
105
DOI
10.1158/1078-0432.CCR-21-1181

A Need for More Molecular Profiling in Brain Metastases.

As local disease control improves, the public health impact of brain metastases (BrM) continues to grow. Molecular features are frequently different between primary and metastatic tumors as a result of clonal evolution during neoplasm migration, selective pressures imposed by systemic treatments, and differences in the local microenvironment. However, biomarker information in BrM is not routinely obtained despite emerging evidence of its clinical value. We review evidence of discordance in clinically actionable biomarkers between primary tumors, extracranial metastases, and BrM. Although BrM biopsy/resection imposes clinical risks, these risks must be weighed against the potential benefits of assessing biomarkers in BrM. First, new treatment targets unique to a patient's BrM may be identified. Second, as BrM may occur late in a patient's disease course, resistance to initial targeted therapies and/or loss of previously identified biomarkers can occur by the time of occult BrM, rendering initial and other targeted therapies ineffective. Thus, current biomarker data can inform real-time treatment options. Third, biomarker information in BrM may provide useful prognostic information for patients. Appreciating the importance of biomarker analyses in BrM tissue, including how it may identify specific drivers of BrM, is critical for the development of more effective treatment strategies to improve outcomes for this growing patient population.
Authors
Shen, E; Van Swearingen, AED; Price, MJ; Bulsara, K; Verhaak, RGW; Baëta, C; Painter, BD; Reitman, ZJ; Salama, AKS; Clarke, JM; Anders, CK; Fecci, PE; Goodwin, CR; Walsh, KM
MLA Citation
Shen, Erica, et al. “A Need for More Molecular Profiling in Brain Metastases.Front Oncol, vol. 11, 2021, p. 785064. Pubmed, doi:10.3389/fonc.2021.785064.
URI
https://scholars.duke.edu/individual/pub1509906
PMID
35145903
Source
pubmed
Published In
Frontiers in Oncology
Volume
11
Published Date
Start Page
785064
DOI
10.3389/fonc.2021.785064