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:

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

Barriers and potential solutions to international collaboration in neuro-oncology clinical trials: Challenges from the Australian perspective.

AIM: The neuro-oncology community in Australia is well positioned to collaborate internationally, with a motivated trials group, strong regulatory bodies and an attractive fiscal environment. We sought to identify gaps in the Australian neuro-oncology clinical trials landscape and describe strategies to increase international trial access in Australia. METHODS: We searched clinical trial registries to identify active adult primary brain cancer trials. We compared the participation rate and phase of these trials between tumour types and countries. A survey was distributed to the Cooperative Trials Group for Neuro-Oncology membership to identify barriers and solutions to effective international collaboration. RESULTS: Globally, 307 trials for adult primary brain cancers were identified. These included 50% pharmaceutical agents, 18% cellular therapies and 9% radiation therapy. Twelve adult primary brain cancer trials were actively recruiting in Australia at the time the survey was sent out. There were more early phase brain cancer trials (34%) compared with colorectal and breast cancer (21% and 24%, respectively). In Australia, 92% of brain cancer trials were involving pharmaceutical agents. The most commonly cited barrier was lack of funding for international trials (86%) and insufficient research time (75%). High ranking solutions included increasing the availability of funding for international trials and creating opportunities to develop personal relationships with collaborators. Accreditation of clinical research key performance indicators into practice (88%) and hospital accreditation (73%) also ranked highly. CONCLUSIONS: Participation in international research in Australia could be improved by embedding clinical research targets into institutional funding, provision of funding for early phase studies and streamlining mutual ethics schemes.
Authors
Kong, BY; Carter, C; Nowak, AK; Hovey, E; Lwin, Z; Haghighi, N; Gan, HK; Sim, H-W; Ziegler, DS; Barton, K; Parkinson, J; Leonard, R; Khasraw, M; Foote, M
MLA Citation
Kong, Benjamin Y., et al. “Barriers and potential solutions to international collaboration in neuro-oncology clinical trials: Challenges from the Australian perspective.Asia Pac J Clin Oncol, June 2021. Pubmed, doi:10.1111/ajco.13606.
URI
https://scholars.duke.edu/individual/pub1486094
PMID
34166569
Source
pubmed
Published In
Asia Pac J Clin Oncol
Published Date
DOI
10.1111/ajco.13606

EPCT-01. A NOVEL PEPTIDE VACCINE DIRECTED TO CMV PP65 FOR TREATMENT OF RECURRENT MALIGNANT GLIOMA AND MEDULLOBLASTOMA IN CHILDREN AND YOUNG ADULTS: PRELIMINARY RESULTS OF A PHASE I TRIAL

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Introduction</jats:title> <jats:p>The cytomegalovirus (CMV) antigen, pp65, is ubiquitously expressed in malignant glioma and medulloblastoma but not in healthy brain. The objective of this Phase I trial (NCT03299309) was to assess the safety and feasibility of a novel pp65 peptide vaccine (PEP-CMV) in children and young adults with recurrent medulloblastoma and malignant glioma.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Vaccines contain a synthetic long peptide (SLP) of 26 amino acids encoding multiple potential class I, class II, and antibody epitopes of CMV pp65 across several haplotypes. This SLP is administered as an emulsion in Montanide ISA 51. Patients receive a single course of temozolomide to induce lymphopenia, tetanus/diphtheria toxoid site preconditioning, then vaccines administered intradermally every two weeks for 3 doses, then monthly.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>To date, 22 patients have been enrolled. Diagnoses include medulloblastoma (n=2), glioblastoma (n=12), anaplastic oligodendroglioma (n=2), anaplastic astrocytoma (n=3), and malignant glioma NOS (n=3). Mean number of prior treatment regimens is 4.9 (range 1–12). Mean age is 22yo (range 6–35) and 45% of patients are male. The median KPS is 80. The median number of vaccines given at time of analysis is 3.3 (range 1–12). There have been no ≥ 3 Grade toxicities related to the vaccine. One patient developed nausea, vomiting, palpitations, and tachycardia after vaccination and had elevated inflammatory cytokines consistent with cytokine release syndrome. Median PFS is 2.5 months (95% CI: 1.7,4.5) and median OS is 6.5 months (95% CI 3.3, 7.9). Immune response to pp65 as determined by ELISpot was found in 75% of patients. On MRI 6 of the 11 evaluable patients have had at least stable disease with three of those having a partial response.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Preliminary results demonstrate that PEP-CMV is well-tolerated and elicits an immune response in heavily pretreated, multiply recurrent patients. A multi-institutional Phase II trial is scheduled to open fall 2021.</jats:p> </jats:sec>
Authors
Thompson, E; Landi, D; Archer, G; Lipp, E; Walter, A; Archambault, B; Balajonda, B; Flahiff, C; Jaggers, D; Herndon, J; Buckley, E; Schroeder, K; Randazzo, D; Desjardins, A; Johnson, M; Peters, K; Khasraw, M; Malinzak, M; Michell, D; Ashley, D; Sampson, J
MLA Citation
Thompson, Eric, et al. “EPCT-01. A NOVEL PEPTIDE VACCINE DIRECTED TO CMV PP65 FOR TREATMENT OF RECURRENT MALIGNANT GLIOMA AND MEDULLOBLASTOMA IN CHILDREN AND YOUNG ADULTS: PRELIMINARY RESULTS OF A PHASE I TRIAL.” Neuro Oncology, vol. 23, no. Supplement_1, Oxford University Press (OUP), 2021, pp. i46–i46. Crossref, doi:10.1093/neuonc/noab090.187.
URI
https://scholars.duke.edu/individual/pub1489722
Source
crossref
Published In
Neuro Oncology
Volume
23
Published Date
Start Page
i46
End Page
i46
DOI
10.1093/neuonc/noab090.187

Leveraging external data in the design and analysis of clinical trials in neuro-oncology.

Integration of external control data, with patient-level information, in clinical trials has the potential to accelerate the development of new treatments in neuro-oncology by contextualising single-arm studies and improving decision making (eg, early stopping decisions). Based on a series of presentations at the 2020 Clinical Trials Think Tank hosted by the Society of Neuro-Oncology, we provide an overview on the use of external control data representative of the standard of care in the design and analysis of clinical trials. High-quality patient-level records, rigorous methods, and validation analyses are necessary to effectively leverage external data. We review study designs, statistical methods, risks, and potential distortions in using external data from completed trials and real-world data, as well as data sources, data sharing models, ongoing work, and applications in glioblastoma.
Authors
Rahman, R; Ventz, S; McDunn, J; Louv, B; Reyes-Rivera, I; Polley, M-YC; Merchant, F; Abrey, LE; Allen, JE; Aguilar, LK; Aguilar-Cordova, E; Arons, D; Tanner, K; Bagley, S; Khasraw, M; Cloughesy, T; Wen, PY; Alexander, BM; Trippa, L
MLA Citation
Rahman, Rifaquat, et al. “Leveraging external data in the design and analysis of clinical trials in neuro-oncology.Lancet Oncol, vol. 22, no. 10, Oct. 2021, pp. e456–65. Pubmed, doi:10.1016/S1470-2045(21)00488-5.
URI
https://scholars.duke.edu/individual/pub1498359
PMID
34592195
Source
pubmed
Published In
Lancet Oncol
Volume
22
Published Date
Start Page
e456
End Page
e465
DOI
10.1016/S1470-2045(21)00488-5

Research Areas:

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