Richard Riedel

Overview:

Novel therapies for soft tissue and bone sarcomas

Positions:

Associate Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2000

Thomas Jefferson University

Resident in Medicine, Medicine

Duke University

Fellow in Hematology-Oncology, Medicine

Duke University

Fellow in Hematology-Oncology, Medicine

Duke University

Grants:

An International, Multicenter, Open-label, Randomized, Phase 3 Study of BLU-285 vs Regorafenib in Patients with Locally Advanced Unresectable or Metastatic Gastrointestinal Stromal Tumor (GIST)

Administered By
Duke Cancer Institute
Awarded By
Blueprint Medicines Corporation
Role
Principal Investigator
Start Date
End Date

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Nirogacestat Versus Placebo in Adult Patients With Progressing Desmoid Tumors/Aggressive Fibromatosis (DT/AF)

Administered By
Duke Cancer Institute
Awarded By
SpringWorks Therapeutics
Role
Principal Investigator
Start Date
End Date

A Phase 3, Interventional, Randomized, Multicenter, Open-Label Study of DCC-2618 vs Sunitinib in Patients with Advanced Gastrointestinal Stromal Tumors after Treatment with Imatinib

Administered By
Duke Cancer Institute
Awarded By
Deciphera Pharmaceuticals, LLC
Role
Principal Investigator
Start Date
End Date

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Determine the Efficacy and Safety of MB305 in Unresectable Locally-advanced or Metastatic NY-ESO-1+ Synovial Sarcoma Subjects Following First-line Systemic Anti-cancer Therapy

Administered By
Duke Cancer Institute
Awarded By
Immune Design Corp.
Role
Principal Investigator
Start Date
End Date

A Phase 1, Dose Escalation Study of Intravenous TK216 in Patients with Relapsed or Refractory Ewing Sarcoma

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

Publications:

Dual energy analysis of TKI response in GIST - results of a prospective trial

Authors
Hohenberger, P; Meyer, M; Henzler, T; Riedel, RF; Messiou, C; Marin, D; Schoenberg, S
MLA Citation
Hohenberger, Peter, et al. “Dual energy analysis of TKI response in GIST - results of a prospective trial.” Cancer Research, vol. 82, no. 12, 2022.
URI
https://scholars.duke.edu/individual/pub1571661
Source
wos-lite
Published In
Cancer Research
Volume
82
Published Date

Hydropneumodissection-Assisted Cryoablation of Recurrent Sarcoma Adjacent to the Sciatic Nerve as a Limb-Sparing Alternative to Hindquarter Amputation.

MLA Citation
Sag, Alan A., et al. “Hydropneumodissection-Assisted Cryoablation of Recurrent Sarcoma Adjacent to the Sciatic Nerve as a Limb-Sparing Alternative to Hindquarter Amputation.J Vasc Interv Radiol, vol. 34, no. 5, May 2023, pp. 923-926.e1. Pubmed, doi:10.1016/j.jvir.2022.12.469.
URI
https://scholars.duke.edu/individual/pub1561049
PMID
36584809
Source
pubmed
Published In
J Vasc Interv Radiol
Volume
34
Published Date
Start Page
923
End Page
926.e1
DOI
10.1016/j.jvir.2022.12.469

Emerging predictive biomarkers in the management of bone and soft tissue sarcomas.

INTRODUCTION: Soft tissue and bone sarcomas are a heterogeneous group of malignancies, each with a unique biology and clinical course. As our understanding of individual sarcoma subtypes and their molecular landscapes increases, predictive biomarkers are emerging to improve patient selection for chemotherapies, targeted therapies, and immunotherapy approaches. AREAS COVERED: This review highlights predictive biomarkers rooted in molecular mechanisms of sarcoma biology, focusing on cell cycle regulation, DNA damage repair, and immune microenvironment interactions. We review CDK4/6 inhibitor predictive biomarkers, including CDKN2A loss, ATRX status, MDM2 levels, and Rb1 status. We discuss homologous recombination deficiency (HRD) biomarkers that predict vulnerability to DNA damage repair (DDR) pathway inhibitors, such as molecular signatures and functional HRD markers. We describe tertiary lymphoid structures and suppressive myeloid cells in the sarcoma immune microenvironment that may influence immunotherapy efficacy. EXPERT OPINION: While predictive biomarkers are not routinely used in sarcoma clinical practice currently, emerging biomarkers are being developed alongside clinical advancements. Novel therapies and predictive biomarkers will be essential for individualizing future approaches to sarcoma management and improving patient outcomes.
Authors
Haddox, CL; Riedel, RF
MLA Citation
Haddox, Candace L., and Richard F. Riedel. “Emerging predictive biomarkers in the management of bone and soft tissue sarcomas.Expert Rev Anticancer Ther, vol. 23, no. 5, May 2023, pp. 495–502. Pubmed, doi:10.1080/14737140.2023.2200169.
URI
https://scholars.duke.edu/individual/pub1571671
PMID
37017995
Source
pubmed
Published In
Expert Rev Anticancer Ther
Volume
23
Published Date
Start Page
495
End Page
502
DOI
10.1080/14737140.2023.2200169

Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors.

BACKGROUND: Desmoid tumors are rare, locally aggressive, highly recurrent soft-tissue tumors without approved treatments. METHODS: We conducted a phase 3, international, double-blind, randomized, placebo-controlled trial of nirogacestat in adults with progressing desmoid tumors according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were assigned in a 1:1 ratio to receive the oral γ-secretase inhibitor nirogacestat (150 mg) or placebo twice daily. The primary end point was progression-free survival. RESULTS: From May 2019 through August 2020, a total of 70 patients were assigned to receive nirogacestat and 72 to receive placebo. Nirogacestat had a significant progression-free survival benefit over placebo (hazard ratio for disease progression or death, 0.29; 95% confidence interval, 0.15 to 0.55; P<0.001); the likelihood of being event-free at 2 years was 76% with nirogacestat and 44% with placebo. Between-group differences in progression-free survival were consistent across prespecified subgroups. The percentage of patients who had an objective response was significantly higher with nirogacestat than with placebo (41% vs. 8%; P<0.001), with a median time to response of 5.6 months and 11.1 months, respectively; the percentage of patients with a complete response was 7% and 0%, respectively. Significant between-group differences in secondary patient-reported outcomes, including pain, symptom burden, physical or role functioning, and health-related quality of life, were observed (P≤0.01). Frequent adverse events with nirogacestat included diarrhea (in 84% of the patients), nausea (in 54%), fatigue (in 51%), hypophosphatemia (in 42%), and maculopapular rash (in 32%); 95% of adverse events were of grade 1 or 2. Among women of childbearing potential receiving nirogacestat, 27 of 36 (75%) had adverse events consistent with ovarian dysfunction, which resolved in 20 women (74%). CONCLUSIONS: Nirogacestat was associated with significant benefits with respect to progression-free survival, objective response, pain, symptom burden, physical functioning, role functioning, and health-related quality of life in adults with progressing desmoid tumors. Adverse events with nirogacestat were frequent but mostly low grade. (Funded by SpringWorks Therapeutics; DeFi ClinicalTrials.gov number, NCT03785964.).
Authors
Gounder, M; Ratan, R; Alcindor, T; Schöffski, P; van der Graaf, WT; Wilky, BA; Riedel, RF; Lim, A; Smith, LM; Moody, S; Attia, S; Chawla, S; D'Amato, G; Federman, N; Merriam, P; Van Tine, BA; Vincenzi, B; Benson, C; Bui, NQ; Chugh, R; Tinoco, G; Charlson, J; Dileo, P; Hartner, L; Lapeire, L; Mazzeo, F; Palmerini, E; Reichardt, P; Stacchiotti, S; Bailey, HH; Burgess, MA; Cote, GM; Davis, LE; Deshpande, H; Gelderblom, H; Grignani, G; Loggers, E; Philip, T; Pressey, JG; Kummar, S; Kasper, B
MLA Citation
Gounder, Mrinal, et al. “Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors.N Engl J Med, vol. 388, no. 10, Mar. 2023, pp. 898–912. Pubmed, doi:10.1056/NEJMoa2210140.
URI
https://scholars.duke.edu/individual/pub1567816
PMID
36884323
Source
pubmed
Published In
The New England Journal of Medicine
Volume
388
Published Date
Start Page
898
End Page
912
DOI
10.1056/NEJMoa2210140

Joint Adult and Pediatric Working Group as a Successful Platform to Strengthen Adolescent and Young Adult (AYA) Clinical Trial Collaboration: A Report from the NCTN/SARC AYA Clinical Trials Sarcoma Working Group.

Authors
Whiteway, SL; Weiss, AR; Ahmed, SK; Allen-Rhoades, WA; Avutu, V; Cardona, K; Davis, LE; Davis, EJ; Indelicato, DJ; Isakoff, MS; Janeway, KA; Livingston, JA; Patel, SR; Reed, DR; Riedel, RF; Thornton, KA; Kopp, LM
URI
https://scholars.duke.edu/individual/pub1565357
PMID
36724495
Source
pubmed
Published In
J Adolesc Young Adult Oncol
Published Date
DOI
10.1089/jayao.2022.0179