Annick Desjardins

Positions:

Professor of Neurosurgery

Neurosurgery, Neuro-Oncology
School of Medicine

Associate Professor in Neurology

Neurology, General & Community Neurology
School of Medicine

Professor in Neurology

Neurology, General & Community Neurology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1998

University of Sherbrooke (Canada)

Resident, Neurology

University of Sherbrooke (Canada)

Fellow in Neuro-Oncology, Medicine

Duke University

Grants:

Phase 3 randomized, open-label study to evaluate Eflornithine with Lomustine compared to Lomustine (STELLAR) alone in patients with Anaplastic Astrocytoma

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

Phase 1 Multicenter, Open-Label, Dose-Escalation, Combination Study of Marizomib and Bevacizumab-Naive Subjects with Grade IV Malignant Glioma

Administered By
Duke Cancer Institute
Awarded By
Celgene Research and Development
Role
Principal Investigator
Start Date
End Date

Phase 1b, Multicenter, Open-Label Study of Marizomib with Temozolomide and Radiotherapy in Patients with Newly Diagnosed WHO Grade IV Malignant Glioma. MRZ112

Administered By
Duke Cancer Institute
Awarded By
Triphase Research and Development Corp
Role
Principal Investigator
Start Date
End Date

A Phase 1 Dose Escalation Study Evaluating the Safety and Tolerability of PF-06840003 in Patients with Malignant Glioma

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

Phase 2 study of SYM004 for adult patients with recurrent glioblastoma

Administered By
Duke Cancer Institute
Awarded By
Symphogen A/S
Role
Principal Investigator
Start Date
End Date

Publications:

A phase 1 study of PF-06840003, an oral indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor in patients with recurrent malignant glioma.

Background PF-06840003 is a highly selective indoleamine 2, 3-dioxygenase (IDO1) inhibitor with antitumor effects in preclinical models. This first-in-human phase 1 study evaluated safety, pharmacokinetics/pharmacodynamics, and preliminary efficacy in recurrent malignant glioma to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Methods Patients (N = 17) received oral PF-06840003 in four dose-escalation groups: 125 mg once-daily (QD; n = 2); 250 mg QD (n = 4); 250 mg twice-daily (BID; n = 3); 500 mg BID (n = 8). A modified toxicity probability interval method determined the MTD. Results Four patients experienced serious adverse events (SAEs); one with treatment-related SAEs (grade 4 alanine and aspartate aminotransferase elevations). The dose-limiting toxicity (DLT) rate at 500 mg BID was 12.5% (n = 1/8); the MTD was not reached. Following PF-06840003 dosing, median time to maximum plasma concentration for the active enantiomer PF-06840002 was 1.5-3.0 hr and mean elimination half-life was 2 to 4 hr (Cycle 1 Day 1). Urinary recovery of PF-06840002 was low (< 1%). At 500 mg BID, maximum mean percentage inhibition of 13C10 kynurenine vs endogenous kynurenine was 75% vs 24%. PF-06840002 CSF-to-plasma ratio was 1.00. Disease control occurred in eight patients (47%). Mean duration of stable disease (SD) was 32.1 (12.1-72.3) weeks. Two patients with SD discontinued the study at 450 and 561 days and continued PF-06840003 on compassionate use. Conclusion PF‑06840003 up to 500 mg BID was generally well tolerated with evidence of a pharmacodynamic effect and durable clinical benefit in a subset of patients with recurrent malignant glioma. ClinicalTrials.gov, NCT02764151, registered April 2016.
Authors
Reardon, DA; Desjardins, A; Rixe, O; Cloughesy, T; Alekar, S; Williams, JH; Li, R; Taylor, CT; Lassman, AB
MLA Citation
Reardon, David A., et al. “A phase 1 study of PF-06840003, an oral indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor in patients with recurrent malignant glioma.Invest New Drugs, vol. 38, no. 6, 2020, pp. 1784–95. Pubmed, doi:10.1007/s10637-020-00950-1.
URI
https://scholars.duke.edu/individual/pub1288223
PMID
32436060
Source
pubmed
Published In
Invest New Drugs
Volume
38
Published Date
Start Page
1784
End Page
1795
DOI
10.1007/s10637-020-00950-1

Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor-beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant glioma.

Purpose Galunisertib, a TGF-β inhibitor, has demonstrated antitumor effects in preclinical and radiographic responses in some patients with malignant glioma. This Phase 1b/2a trial investigated the clinical benefit of combining galunisertib with temozolomide-based radiochemotherapy (TMZ/RTX) in patients with newly diagnosed malignant glioma (NCT01220271). Methods This is an open-label, 2-arm Phase 1b/2a study (N = 56) of galunisertib (intermittent dosing: 14 days on/14 days off per cycle of 28 days) in combination with TMZ/RTX (n = 40), versus a control arm (TMZ/RTX, n = 16). The primary objective of Phase 1b was to determine the safe and tolerable Phase 2 dose of galunisertib. The primary objective of Phase 2a was to confirm the tolerability and pharmacodynamic profile of galunisertib with TMZ/RTX, and the secondary objectives included determining the efficacy and pharmacokinetic (PK) profile of galunisertib with TMZ/RTX in patients with glioblastoma. This study also characterized the changes in the major T-cell subsets during TMZ/RTX plus galunisertib treatment. Results In the Phase 2a study, efficacy results for patients treated with galunisertib plus TMZ/RTX or TMZ/RTX were: median overall survival (18.2 vs 17.9 months), median progression-free survival (7.6 vs 11.5 months), and disease control rate (80% [32/40] vs 56% [9/16] patients) respectively. PK profile of galunisertib plus TMZ/RTX regimen was consistent with previously published PK data of galunisertib. The overall safety profile across treatment arms was comparable. Conclusion No differences in efficacy, safety or pharmacokinetic variables were observed between the two treatment arms.
Authors
Wick, A; Desjardins, A; Suarez, C; Forsyth, P; Gueorguieva, I; Burkholder, T; Cleverly, AL; Estrem, ST; Wang, S; Lahn, MM; Guba, SC; Capper, D; Rodon, J
URI
https://scholars.duke.edu/individual/pub1434005
PMID
32140889
Source
pubmed
Published In
Invest New Drugs
Volume
38
Published Date
Start Page
1570
End Page
1579
DOI
10.1007/s10637-020-00910-9

Rindopepimut with Bevacizumab for Patients with Relapsed EGFRvIII-Expressing Glioblastoma (ReACT): Results of a Double-Blind Randomized Phase II Trial.

PURPOSE: Rindopepimut is a vaccine targeting the tumor-specific EGF driver mutation, EGFRvIII. The ReACT study investigated whether the addition of rindopepimut to standard bevacizumab improved outcome for patients with relapsed, EGFRvIII-positive glioblastoma. PATIENTS AND METHODS: In this double-blind, randomized, phase II study (NCT01498328) conducted at 26 hospitals in the United States, bevacizumab-naïve patients with recurrent EGFRvIII-positive glioblastoma were randomized to receive rindopepimut or a control injection of keyhole limpet hemocyanin, each concurrent with bevacizumab. The primary endpoint was 6-month progression-free survival (PFS6) by central review with a one-sided significance of 0.2. RESULTS: Between May 2012 and 2014, 73 patients were randomized (36 rindopepimut, 37 control). Rindopepimut toxicity included transient, low-grade local reactions. As primary endpoint, PFS6 was 28% (10/36) for rindopepimut compared with 16% (6/37) for control (P = 0.12, one-sided). Secondary and exploratory endpoints also favored the rindopepimut group including a statistically significant survival advantage [HR, 0.53; 95% confidence interval (CI), 0.32-0.88; two-sided log-rank P = 0.01], a higher ORR [30% (9/30) vs. 18% (6/34; P = 0.38)], median duration of response [7.8 months (95% CI, 3.5-22.2) vs. 5.6 (95% CI, 3.7-7.4)], and ability to discontinue steroids for ≥6 months [33% (6/18) vs. 0% (0/19)]. Eighty percent of rindopepimut-treated patients achieved robust anti-EGFRvIII titers (≥1:12,800), which were associated with prolonged survival (HR = 0.17; 95% CI, 0.07-0.45; P < 0.0001). CONCLUSIONS: Our randomized trial supports the potential for targeted immunotherapy among patients with GBM, but the therapeutic benefit requires validation due to the small sample size and potential heterogeneity of bevacizumab response among recurrent patients with GBM.See related commentary by Wick and Wagener, p. 1535.
Authors
Reardon, DA; Desjardins, A; Vredenburgh, JJ; O'Rourke, DM; Tran, DD; Fink, KL; Nabors, LB; Li, G; Bota, DA; Lukas, RV; Ashby, LS; Duic, JP; Mrugala, MM; Cruickshank, S; Vitale, L; He, Y; Green, JA; Yellin, MJ; Turner, CD; Keler, T; Davis, TA; Sampson, JH; ReACT trial investigators,
MLA Citation
Reardon, David A., et al. “Rindopepimut with Bevacizumab for Patients with Relapsed EGFRvIII-Expressing Glioblastoma (ReACT): Results of a Double-Blind Randomized Phase II Trial.Clin Cancer Res, vol. 26, no. 7, Apr. 2020, pp. 1586–94. Pubmed, doi:10.1158/1078-0432.CCR-18-1140.
URI
https://scholars.duke.edu/individual/pub1431799
PMID
32034072
Source
pubmed
Published In
Clinical Cancer Research
Volume
26
Published Date
Start Page
1586
End Page
1594
DOI
10.1158/1078-0432.CCR-18-1140

Second primary cancers in long-term survivors of glioblastoma.

Background: Overall survival (OS) in glioblastoma (GBM) is poor at an average of 14 to 18 months, and long-term survivors (LTS) of GBM are rare. LTS of GBM, defined as surviving >5 years postdiagnosis, represent only 2% to 10% of all GBM patients. LTS of cancer are at high risk of developing second primary neoplasms. This study looks at occurrences of second primary neoplasms in LTS of GBM. Methods: Records from adult patients newly diagnosed with GBM between January 1, 1998 and February 8, 2010, were retrospectively reviewed to identify LTS, defined as patients who survived ≥5 years. We focused on the identification of a new diagnosis of cancer occurring at least 2 years after the initial GBM diagnosis. Results: We identified 155 LTS of GBM, with a median OS of 11.0 years (95% CI: 9.0 to 13.1 years) and a median follow-up of 9.6 years (95% CI: 8.7 to 10.7 years). In this cohort of patients, 13 (8.4%) LTS of GBM developed 17 secondary cancers. Eight could potentially be attributed to previous radiation and chemotherapy (skin cancer in radiation field [n = 4], leukemia [n = 2], low-grade glioma [n = 1], and sarcoma of the scalp [n = 1]). The other 9 cases included melanoma (n = 2), prostate cancer (n = 2), bladder cancer (n = 1), endometrioid adenocarcinoma (n = 1), basal cell carcinoma (n = 1), and renal cell carcinoma (n = 1). Conclusions: Although second primary cancers are rare in GBM LTS, providers should continue close monitoring with appropriate oncologic care. Moreover, this highlights the need for survivorship care of patients with GBM.
Authors
Kim, J-Y; Jackman, JG; Woodring, S; McSherry, F; Herndon, JE; Desjardins, A; Friedman, HS; Peters, KB
MLA Citation
Kim, Jung-Young, et al. “Second primary cancers in long-term survivors of glioblastoma.Neurooncol Pract, vol. 6, no. 5, Sept. 2019, pp. 386–91. Pubmed, doi:10.1093/nop/npz001.
URI
https://scholars.duke.edu/individual/pub1411790
PMID
31555453
Source
pubmed
Published In
Neuro Oncology Practice
Volume
6
Published Date
Start Page
386
End Page
391
DOI
10.1093/nop/npz001

Randomized open-label phase II trial of 5-day aprepitant plus ondansetron compared to ondansetron alone in the prevention of chemotherapy-induced nausea-vomiting (CINV) in glioma patients receiving adjuvant temozolomide.

PURPOSE: CINV remains a distressing side effect experienced by glioma patients receiving multi-day temozolomide therapy, in spite of guideline-based antiemetic therapy with selective serotonin-receptor-antagonists. Antiemetic research with aprepitant has routinely excluded glioma patients. In this randomized open-label phase II study, use of a nonstandard 5-day regimen of aprepitant for glioma patients was investigated. METHODS: One hundred thirty-six glioma patients receiving their first cycle of adjuvant temozolomide (150-200 mg/m2/day × 5 days every 28 days) were randomized to Arm-A (ondansetron 8 mg days 1-5 with aprepitant day 1: 125 mg, days 2-5: 80 mg) or Arm-B (ondansetron). Randomization was stratified by tumor grade and number of prior chemotherapy regimens. The primary endpoint was the percentage of patients achieving complete control (CC), defined as no emetic episode or antiemetic rescue medication over the 7-day study period. Secondary endpoints included CINV efficacy in the acute phase (≤ 24 h) and delayed phase (days 2-7), as well as safety and quality of life (QoL). RESULTS: Patients were 61% male, 97% white, 48% with KPS > 90%, 60% non-smokers, mean age 54, 92% with low alcohol use, and 46% with a CINV history. The CC was 58.6% (Arm-A) and 54.5% (Arm-B). Acute-complete response (CR) rates, defined as CC on day 1 in Arm-A and -B, were 97.1% and 87.9%, respectively (p = 0.056). Treatment-related toxicities were mild or moderate in severity. CONCLUSIONS: Aprepitant plus ondansetron may increase acute-CR, may have benefit regarding CINV's effect on QoL, and is safe for 5-day temozolomide compared to ondansetron. This study provides no evidence that aprepitant increases CC rate over ondansetron alone.
Authors
Patel, MP; Woodring, S; Randazzo, DM; Friedman, HS; Desjardins, A; Healy, P; Herndon, JE; McSherry, F; Lipp, ES; Miller, E; Peters, KB; Affronti, ML
MLA Citation
URI
https://scholars.duke.edu/individual/pub1406357
PMID
31440823
Source
pubmed
Published In
Support Care Cancer
Volume
28
Published Date
Start Page
2229
End Page
2238
DOI
10.1007/s00520-019-05039-x