Mustafa Khasraw

Overview:

I am a medical oncologist, neuro-oncologist, tenured professor of medicine and neurooncology, and Deputy Director of the Center for Cancer Immunotherapy, Duke Cancer Institute, where are tasked to speed up clinical research and translation for scientists across all departments and all tumor types at Duke, who have made discoveries that show promise for developing new immunotherapies.

I am leading several clinical and translational programs with significant laboratory collaborations with an interest in innovative trials designed to improve the outcome of patients with cancers of the CNS. In addition, I am the principal investigator on first in human phase I immunotherapy clinical trials in solid tumors. 

I serve as an advisor and grant reviewer for several non-profits and patient advocacy groups. I am a Fellow of the Royal Australasian College of Physicians and an Elected Fellow of the Royal College of Physicians (UK). 

Positions:

Professor of Neurosurgery

Neurosurgery
School of Medicine

Professor in Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2001

Rijksuniversiteit Groningen (The Netherlands)

Grants:

Astellas 1951-CL-0101

Administered By
Duke Cancer Institute
Awarded By
Astellas Pharma Global Development, Inc
Role
Principal Investigator
Start Date
End Date

Celldex CDX-527

Administered By
Duke Cancer Institute
Awarded By
Celldex Therapeutics, Inc.
Role
Principal Investigator
Start Date
End Date

Publications:

Glioblastoma Clinical Trials: Current Landscape and Opportunities for Improvement.

Therapeutic advances for glioblastoma have been minimal over the past 2 decades. In light of the multitude of recent phase III trials that have failed to meet their primary endpoints following promising preclinical and early-phase programs, a Society for Neuro-Oncology Think Tank was held in November 2020 to prioritize areas for improvement in the conduct of glioblastoma clinical trials. Here, we review the literature, identify challenges related to clinical trial eligibility criteria and trial design in glioblastoma, and provide recommendations from the Think Tank. In addition, we provide a data-driven context with which to frame this discussion by analyzing key study design features of adult glioblastoma clinical trials listed on ClinicalTrials.gov as "recruiting" or "not yet recruiting" as of February 2021.
Authors
Bagley, SJ; Kothari, S; Rahman, R; Lee, EQ; Dunn, GP; Galanis, E; Chang, SM; Nabors, LB; Ahluwalia, MS; Stupp, R; Mehta, MP; Reardon, DA; Grossman, SA; Sulman, EP; Sampson, JH; Khagi, S; Weller, M; Cloughesy, TF; Wen, PY; Khasraw, M
MLA Citation
Bagley, Stephen J., et al. “Glioblastoma Clinical Trials: Current Landscape and Opportunities for Improvement.Clin Cancer Res, Sept. 2021. Pubmed, doi:10.1158/1078-0432.CCR-21-2750.
URI
https://scholars.duke.edu/individual/pub1497056
PMID
34561269
Source
pubmed
Published In
Clinical Cancer Research
Published Date
DOI
10.1158/1078-0432.CCR-21-2750

Reply to: 'Real-world prevalence across 159 872 patients with cancer supports the clinical utility of TMB-H to define metastatic solid tumors for treatment with pembrolizumab.' by D. Fabrizio et al.

Authors
McGrail, DJ; Pilié, PG; Rashid, NU; Voorwerk, L; Slagter, M; Kok, M; Jonasch, E; Khasraw, M; Heimberger, AB; Ueno, NT; Ferrarotto, R; Chang, JT; Lin, S-Y
MLA Citation
URI
https://scholars.duke.edu/individual/pub1486095
PMID
34166757
Source
pubmed
Published In
Ann Oncol
Volume
32
Published Date
Start Page
1194
End Page
1197
DOI
10.1016/j.annonc.2021.06.017

Immune Microenvironment Landscape in CNS Tumors and Role in Responses to Immunotherapy.

Despite the important evolution of immunotherapeutic agents, brain tumors remain, in general, refractory to immune therapeutics. Recent discoveries have revealed that the glioma microenvironment includes a wide variety of immune cells in various states that play an important role in the process of tumorigenesis. Anti-tumor immune activity may be occurring or induced in immunogenic hot spots or at the invasive edge of central nervous system (CNS) tumors. Understanding the complex heterogeneity of the immune microenvironment in gliomas will likely be the key to unlocking the full potential of immunotherapeutic strategies. An essential consideration will be the induction of immunological effector responses in the setting of the numerous aspects of immunosuppression and evasion. As such, immune therapeutic combinations are a fundamental objective for clinical studies in gliomas. Through immune profiling conducted on immune competent murine models of glioma and ex vivo human glioma tissue, we will discuss how the frequency, distribution of immune cells within the microenvironment, and immune modulatory processes, may be therapeutically modulated to lead to clinical benefits.
Authors
Najem, H; Khasraw, M; Heimberger, AB
MLA Citation
Najem, Hinda, et al. “Immune Microenvironment Landscape in CNS Tumors and Role in Responses to Immunotherapy.Cells, vol. 10, no. 8, Aug. 2021. Epmc, doi:10.3390/cells10082032.
URI
https://scholars.duke.edu/individual/pub1494261
PMID
34440802
Source
epmc
Published In
Cells
Volume
10
Published Date
DOI
10.3390/cells10082032

Clinical Trials with Biologic Primary Endpoints in Immuno-oncology: Concepts and Usage.

Clinical trials that have a pharmacokinetic or a pharmacodynamic immunologic mechanism of action-based primary outcome could substantially improve the validity and efficiency of early development of immuno-oncology agents. Here, we outline different trial design options in this area, review examples from the literature and their unique immunologic aspects, and highlight how these trials have been underutilized. We illustrate how new technologies and translationally focused approaches can be successfully used to develop different classes of immunotherapeutic agents.
Authors
Isaacs, J; Tan, AC; Hanks, BA; Wang, X; Owzar, K; Herndon, JE; Antonia, SJ; Piantadosi, S; Khasraw, M
MLA Citation
Isaacs, James, et al. “Clinical Trials with Biologic Primary Endpoints in Immuno-oncology: Concepts and Usage.Clin Cancer Res, July 2021. Pubmed, doi:10.1158/1078-0432.CCR-21-1593.
URI
https://scholars.duke.edu/individual/pub1489704
PMID
34312214
Source
pubmed
Published In
Clinical Cancer Research
Published Date
DOI
10.1158/1078-0432.CCR-21-1593

Systematic review of combinations of targeted or immunotherapy in advanced solid tumors.

With rapid advances in our understanding of cancer, there is an expanding number of potential novel combination therapies, including novel-novel combinations. Identifying which combinations are appropriate and in which subpopulations are among the most difficult questions in medical research. We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic review of trials of novel-novel combination therapies involving immunotherapies or molecular targeted therapies in advanced solid tumors. A MEDLINE search was conducted using a modified Cochrane Highly Sensitive Search Strategy for published clinical trials between July 1, 2017, and June 30, 2020, in the top-ranked medical and oncology journals. Trials were evaluated according to a criterion adapted from previously published Food and Drug Administration guidance and other key considerations in designing trials of combinations. This included the presence of a strong biological rationale, the use of a new established or emerging predictive biomarker prospectively incorporated into the clinical trial design, appropriate comparator arms of monotherapy or supportive external data sources and a primary endpoint demonstrating a clinically meaningful benefit. Of 32 identified trials, there were 11 (34%) trials of the novel-novel combination of anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) therapy, and 10 (31%) trials of anti-PD-1/PD-L1 and anti-vascular endothelial growth factor (VEGF) combination therapy. 20 (62.5%) trials were phase II trials, while 12 (37.5%) were phase III trials. Most (72%) trials lacked significant preclinical evidence supporting the development of the combination in the given indication. A majority of trials (69%) were conducted in biomarker unselected populations or used pre-existing biomarkers within the given indication for patient selection. Most studies (66%) were considered to have appropriate comparator arms or had supportive external data sources such as prior studies of monotherapy. All studies were evaluated as selecting a clinically meaningful primary endpoint. In conclusion, designing trials to evaluate novel-novel combination therapies presents numerous challenges to demonstrate efficacy in a comprehensive manner. A greater understanding of biological rationale for combinations and incorporating predictive biomarkers may improve effective evaluation of combination therapies. Innovative statistical methods and increasing use of external data to support combination approaches are potential strategies that may improve the efficiency of trial design. Designing trials to evaluate novel-novel combination therapies presents numerous challenges to demonstrate efficacy in a comprehensive manner. A greater understanding of biological rationale for combinations and incorporating predictive biomarkers may improve effective evaluation of combination therapies. Innovative statistical methods and increasing use of external data to support combination approaches are potential strategies that may improve the efficiency of trial design.
Authors
Tan, AC; Bagley, SJ; Wen, PY; Lim, M; Platten, M; Colman, H; Ashley, DM; Wick, W; Chang, SM; Galanis, E; Mansouri, A; Khagi, S; Mehta, MP; Heimberger, AB; Puduvalli, VK; Reardon, DA; Sahebjam, S; Simes, J; Antonia, SJ; Berry, D; Khasraw, M
MLA Citation
Tan, Aaron C., et al. “Systematic review of combinations of targeted or immunotherapy in advanced solid tumors.J Immunother Cancer, vol. 9, no. 7, July 2021. Pubmed, doi:10.1136/jitc-2021-002459.
URI
https://scholars.duke.edu/individual/pub1488074
PMID
34215688
Source
pubmed
Published In
Journal for Immunotherapy of Cancer
Volume
9
Published Date
DOI
10.1136/jitc-2021-002459

Research Areas:

Anti-cancer
Cancer
Cancer Therapy Resistance
Cancer Vaccines
Cancer genes
Cancer--Immunotherapy
Immunotherapy