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A Phase 1, Multicenter, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Orally Administered AG-120 in Subjects With Advanced Solid Tumors, Including Glioma, With an IDH1 Mutation

Trial Profile

A Phase 1, Multicenter, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Orally Administered AG-120 in Subjects With Advanced Solid Tumors, Including Glioma, With an IDH1 Mutation

Status: Active, no longer recruiting
Phase of Trial: Phase I

Latest Information Update: 12 Jun 2020

At a glance

  • Drugs Ivosidenib (Primary)
  • Indications Astrocytoma; Cholangiocarcinoma; Chondrosarcoma; Glioma; Oligodendroglioma; Solid tumours
  • Focus Adverse reactions
  • Sponsors Agios Pharmaceuticals
  • Most Recent Events

    • 12 Jun 2020 Results (data cutoff date January 16, 2019; n=66) determining safety and tolerability of oral ivosidenib as a single agent in patients with glioma, published in the Journal of Clinical Oncology
    • 24 Mar 2020 Results (n=21) assessing safety and clinical activity in patients With advanced chondrosarcoma, published in the Journal of Clinical Oncology
    • 26 Apr 2019 Results (n=168, data cut off: May 12, 2017) published in the Investigational New Drugs

Trial Overview

Purpose

This study is investigating the safety, tolerability, pharmacokinetics and pharmacodynamics of AG-120 in patients with IDH1 mutated advanced solid tumours, including glioma.
This study is divided in two parts, first part is dose escalation and second part is dose expansion.
AG-120 was administered at the following dose levels and schedules in the dose-escalation cohort: 100 mg twice daily, and 300, 400, 500, 800 and 1200 mg once a day over a 28 day cycle length. In the dose expansion cohort, patients received 500 mg once a day.

Primary Endpoints

Safety/tolerability: incidence of adverse events

safety_issue: Yes
time_frame: Up to 26 weeks, on average

Maximum Tolerated Dose and/or the recommended Phase II dose of AG-120 in subjects with advanced solid tumors, including glioma

safety_issue: Yes
time_frame: Up to 26 weeks, on average

Other Endpoints

Dose Limiting Toxicities of AG-120 in subjects with advanced solid tumors, including glioma

safety_issue: Yes time_frame: Up to 26 weeks, on average

Pharmacokinetics of AG-120 in subjects with advanced solid tumors, including glioma

safety_issue: Yes description: Descriptive statistics will be used to summarize PK parameters for each dose group and, where appropriate, for the entire population. Such parameters will include max concentration (Cmax), time to maximum concentration (Tmax), AUC, elimination half-life. time_frame: Up to 26 weeks, on average

Pharmacodynamic relationship of AG-120 and 2-HG

safety_issue: Yes description: PD parameters will be summarized using the following descriptive statistics: n, Mean, SD, CV%, Median, Min, and Max, GeoMean, and GeoCV%. PK/PD correlations between exposure to AG-120 and the extent of suppression of 2-HG will be explored using graphical display of data. time_frame: Up to 26 weeks, on average

Clinical Activity associated with AG-120 in subjects with advanced solid tumors, including glioma

safety_issue: Yes description: The clinical activity of AG-120 will be evaluated by assessing response to treatment according to RECIST v1.1 for subjects without glioma or by modified RANO criteria for subjects with glioma time_frame: Up to 26 weeks, on average [1]

Diseases Treated

Indication Qualifiers Patient Segments
Astrocytoma treatment high grade, low grade, stage III, stage IV
Cholangiocarcinoma treatment second-line or greater therapy, stage II, stage III, stage IV
Chondrosarcoma treatment stage III, stage IV
Glioma treatment second-line or greater therapy, stage III, stage IV
Oligodendroglioma - high grade, low grade, stage III, stage IV
Solid tumours treatment first-line therapy, stage III, stage IV

Subjects

  • Subject Type patients
  • Number

    Planned: 170

    Actual: 168

  • Sex male & female
  • Age Group ≥ 18 years; adult; elderly

Patient Inclusion Criteria

Key 1. Dose Escalation 1. Subjects must have histologically or cytologically confirmed, IDH1 gene-mutated advanced solid tumors, including glioma, that have recurred or progressed following standard therapy, or that have not responded to standard therapy. 2. Subjects must have evaluable disease by RECIST v1.1 for subjects without glioma or by RANO criteria for subjects with glioma. 2. Dose Expansion: Cholangiocarcinoma 1. Subjects must have histologically-confirmed diagnosis of IDH1 gene-mutated cholangiocarcinoma Stage II, III, or IV (intra-hepatic, extra-hepatic and perihilar) that is not eligible for curative resection, transplantation, or ablative therapies. Tumors of mixed histology are not allowed. 2. Cholangiocarcinoma subjects must have progressed following gemcitabine-based regimen. 3. Cholangiocarcinoma subjects must have radiographically measurable disease in at least one site not previously treated with radiation, chemoembolization, radioembolization, or other local ablative procedures; a new area of tumor progression within or adjacent to a previously-treated lesion, if clearly measurable by a radiologist, is acceptable. 3. Dose Expansion: Chondrosarcoma a. Subjects must have IDH1 gene-mutated chondrosarcoma that is either locally advanced or metastatic and not amenable to complete surgical excision. 4. Dose Expansion: Non-enhancing Glioma 1. Subjects must have progressive glioma that is solely non-enhancing on MRI. 2. Progression of glioma must have occurred over 12 months or less. 3. Subject must have available at least 3 prior full sets of scans (not including screening), each separated by at least 2 months with less than or equal to 5 mm slice thickness and up to 1 mm interslice gap on either 2D T2 weighted image, 3D T2 weighted image, or FLAIR. 4. Subjects must not have had prior surgery (biopsy allowed) or radiation therapy within 6 months of enrollment. 5. Dose Expansion: Solid Tumors Not Otherwise Eligible for the Cholangiocarcinoma, Chondrosarcoma, or Non-enhancing Glioma Cohorts 1. IDH1 gene-mutated solid tumors refractory to conventional therapy or the subject does not tolerate the conventional therapy 2. Subjects must have radiographically measurable disease in at least one site not previously treated with radiation, chemoembolization, radioembolization, or other local ablative procedures; a new area of tumor progression within or adjacent to a previously-treated lesion, if clearly measurable by a radiologist, is acceptable. 6. Subject must be ≥18 years of age. 7. Subjects must have documented IDH1 gene-mutated disease based on local test evaluation. (Centralized testing will be performed retrospectively.) 8. Subjects must be amenable to serial peripheral blood sampling, urine sampling, and biopsies during the study. 9. Subject must be able to understand and willing to sign an informed consent. A legally authorized representative may consent on behalf of a subject who is otherwise unable to provide informed consent, if acceptable to and approved by the site and/or site's Institutional Review Board (IRB)/Independent Ethics Committee (IEC). 10. Subjects must have ECOG PS of 0 to 1. 11. Subjects must have expected survival of ≥3 months. 12. Subjects must have adequate bone marrow function as evidenced by: 1. Absolute neutrophil count ≥1.5 ×109/L; 2. Hemoglobin >9 g/dL (Subjects are allowed to be transfused to this level) 3. Platelets ≥ 75 × 109/L. 13. Subjects must have adequate hepatic function as evidenced by: 1. Serum total bilirubin ≤1.5 × upper limit of normal (ULN), unless considered due to Gilbert's disease or disease involvement following approval by the Medical Monitor; 2. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤2.5 × ULN. For subjects with bone metastases and/or suspected disease-related liver or biliary involvement, ALP must be ≤5 × ULN. 14. Subjects must have adequate renal function as evidenced by: a. Serum creatinine ≤2.0 × ULN OR b. Creatinine clearance >40 mL/min based on the Cockcroft-Gault glomerular filtration rate (GFR) estimation: (140 - Age) x (weight in kg) x (0.85 if female)/72 x serum creatinine 15. Subjects must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer. (For example, subjects with residual Grade 1 toxicity or stable Grade 2 peripheral neuropathy due to prior chemotherapy are allowed with approval of the Medical Monitor.) 16. Female subjects with reproductive potential must agree to undergo medically supervised pregnancy test prior to starting study drug. The first pregnancy test will be performed at screening (within 7 days prior to first study drug administration), and on the day of the first study drug administration and confirmed negative prior to dosing. Subjects with reproductive potential are defined as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy or tubal occlusion or who have not been naturally postmenopausal (i.e., who have not menstruated at all) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). Females of reproductive potential, as well as fertile men with partners who are female of reproductive potential, must agree to abstain from sexual intercourse or to use two highly effective forms of contraception from the time of giving informed consent, during the study and for 90 days (females and males) following the last dose of AG-120. A highly effective form of contraception is defined as hormonal oral contraceptives, injectables, patches, intrauterine devices, double-barrier method (e.g., synthetic condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), or male partner sterilization.

Patient Exclusion Criteria

1. Subjects who received systemic anticancer therapy or radiotherapy <21 days prior to their first day of study drug administration. 2. Subjects who received an investigational agent <14 days prior to their first day of study drug administration. In addition, the first dose of AG-120 should not occur before a period ≥5 half-lives of the investigational agent has elapsed. 3. Subjects taking the following sensitive cytochrome P450 (CYP) 3A4 substrate medications are excluded from the study unless they can be transferred to other medications prior to enrolling: alfentanil, aprepitant, budesonide, buspirone, conivaptan, darifenacin, darunavir, dronedarone, eletriptan, eplerenone, felodipine, indinavir, fluticasone, lopinavir, lovastatin, lurasidone, maraviroc, midazolam, nisoldipine, quetiapine, saquinavir, sildenafil, simvastatin, tolvaptan, tipranavir, triazolam, ticagrelor, vardenafil and/or the CYP2B6 substrates: bupropion, efavirenz. 4. Subjects taking the following P-glycoprotein (P-gp) transporter-sensitive substrate medications are excluded from the study unless they can be transferred to other medications prior to enrolling: aliskiren, ambrisentan, colchicine, dabigatran etexilate, digoxin, fexofenadine, maraviroc, posaconazole, ranolazine, saxagliptin, sitagliptin, talinolol, and tolvaptan. 5. Subjects for whom potentially curative anticancer therapy is available. 6. Subjects who are pregnant or breast feeding. 7. Subjects with an active severe infection that required anti-infective therapy or with an unexplained fever >38.5°C during screening visits or on their first day of study drug administration (at the discretion of the Investigator, subjects with tumor fever may be enrolled). 8. Subjects with known hypersensitivity to any of the components of AG-120. 9. Subjects with New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF <40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan within approximately 28 days of C1D1. 10. Subjects with a history of myocardial infarction within the last 6 months. 11. Subjects with known unstable or uncontrolled angina pectoris. 12. Subjects with a known history of severe and/or uncontrolled ventricular arrhythmias. 13. Subjects with heart-rate corrected QT (QTc) interval ≥ 450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome). Subjects with right bundle branch block and a prolonged QTc interval should be reviewed by the Medical Monitor for potential inclusion. 14. Subjects taking medications that are known to prolong the QT interval (see Section 9.11.3). 15. Subjects with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C. 16. Subjects with any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate, or participate in the study. 17. Subjects with known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally. 18. Subjects with brain metastases that are untreated, symptomatic, or require therapy to control symptoms; or any radiation, surgery, or other therapy, including those used to control symptoms, within 2 months of first dose. Subjects with glioma who are on a stable, steroid dosing regimen 5 days prior to the screening MRI may be permitted to enroll with Medical Monitor approval. 19. Subjects with a history of Grade 4 astrocytoma (applicable only to subjects enrolled in the dose expansion non-enhancing glioma cohort).

Trial Details

Identifiers

Identifier Owner
NCT02073994 ClinicalTrials.gov: US National Institutes of Health
14-068 Memorial Sloan-Kettering Cancer Center
AG120C002 -

Organisations

  • Sponsors Agios Pharmaceuticals
  • Affiliations Agios Pharmaceuticals

Trial Dates

  • Initiation Dates

    Actual : 14 Mar 2014

  • Primary Completion Dates

    Planned : 01 Jun 2021

  • End Dates

    Planned : 01 Jun 2021

Other Details

  • Design multicentre; open; prospective
  • Phase of Trial Phase I
  • Location France; USA
  • Focus Adverse reactions

Interventions

Drugs Route Formulation
IvosidenibPrimary Drug Oral Tablet

AG-120 (100 mg twice daily and 300, 400, 500, 600, 800, 900, and 1,200 mg once daily)

AG-120 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with AG-120 until disease progression, development of other unacceptable toxicity or Investigator discretion.
Drug: AG-120 (AG-120 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects may continue treatment with AG-120 until disease progression or development of other unacceptable toxicity)

Results

Therapeutic efficacy

Phase I: Updated results of the dose expansion cohort of the phase I study of ivosidenib in patients (n = 35) with progressive low grade isocitrate dehydrogenase-1 mutant (IDH1m) glioma showed durable stable disease and reduction of tumour growth rates observed for patients with low grade glioma, median treatment duration of 16 months (range 1.4 – 27.1 months), with 51% (18/35) of patients remaining on treatment. A daily dose of 500 mg ivosidenib was selected as the expansion dose. The median progression free survival (PFS) for all non-enhancing patients was 13 months, the median PFS for Grade 2 patients (n = 24) was not reached. For patients in the expansion arm (n=24), the average six-month tumour growth was 24% prior to treatment and 11% following treatment with ivosidenib [2] . Treatment of ivosidenib, in patients (n = 73) with IDH1 mutant positive cholangiocarcinoma showed partial response in four patients (5%), at the dose level of 300 mg and 500 mg. Stable disease was demonstrated in 41 patients (56%). The progression free survival observed at six (PFS6) and 12 months (PFS12) were 38.5% and 20.7% respectively. The median progression free survival (PFS) was 3.8 months (95% CI 3.6, 7.3) [3] . Interim results of patients (n = 66) with IDH-1 mutant positive glioma and chondrosarcoma, ivosidenib showed 63% patients with stable disease including 27 patients with non-enhancing disease. The volumetric analysis conducted centrally demonstrated stabilisation or a decrease in tumour growth rate, compared to the pretreatment rate, in 64% (n=14 of 22) of glioma patients with non-enhancing disease receiving ivosidenib. The three-month progression free survival rate observed was 58% [4] .

Adverse events

Phase I: Updated results of the dose expansion cohort of the phase I study in patients (n = 35) with progressive low grade isocitrate dehydrogenase-1 mutant (IDH1m) glioma demonstrated that ivosidenib was well-tolerated with no dose limiting toxicities, and a favourable safety profile in glioma patients. The majority of adverse events (AEs) reported were mild to moderate, and the most common AEs included headache, diarrhoea, nausea and vomiting. There were five patients with serious adverse events (SAEs), but all were deemed unrelated to study treatment [2] . Interim results of patients (n = 73) with IDH1 mutant positive cholangiocarcinoma, was safe and well-tolerated with the favourable safety profile observed. Dose limiting toxicities or treatment-related deaths were not reported. Two patients experienced drug related AEs as fatigue (n=1) and blood alkaline phosphatase increases (n=1), at the dose level of 500 mg. While at the dose level of 1200 mg, two patients experienced drug-related AEs as fatigue (n=1) and blood phosphorous decreases (n=1). One grade two, possibly drug-related AE of worsening leg cramps was observed, for which dose reduction was done for the patient. Interim results of patients (n = 66) with IDH-1 mutant positive glioma and chondrosarcoma showed that the adverse events reported were mild to moderate in nature and commonly observed were headache, nausea, diarrhoea, decreased appetite, QT-prolongation, fatigue and vomiting. There were 11 patients with serious adverse events none of them were drug related and one case of serious adverse event hypophosphataemia was considered to be possibly related to the treatment [3] [4] .

Pharmacokinetics

Updated results from a phase I study in mIDH1 advanced solid tumours including cholangiocarcinoma showed rapid absorption, good oral exposure and a bi-exponential decline in plasma levels of ivosidenib post single and multiple dose administration. The mean terminal half-life was 40–102 hours. Steady state was achieved within 14 days, along with a moderate accumulation (1.5- to 1.7-fold for AUC at 500 mg QD) in plasma ivosidenib exposure. Ivosidenib exposure and Ivosidenib clearance were unaffected by intrinsic factors and mild/moderate renal impairment, mild hepatic impairment, and concomitant administration of weak CYP3A4 inhibitors/inducers, respectively. The results were reported from 168 patients [5] [6] .

Pharmacodynamics

Phase I: Data from the phase I trial for ivosidenib, conducted in patients with IDH1 mutant positive cholangiocarcinoma, showed morphologic changes suggestive of cellular differentiation which is consistent with the proposed mechanism of action of the drug [3] . Additional data demonstrated that post multiple dosing, plasma 2-HG (oncometabolite D-2-hydroxyglutarate) levels were reduced (up to 98.4% inhibition, achieving levels similar to those in healthy volunteers) and tumour biopsy 2-HG levels were also substantially reduced (by up to 99.9%) at all dose levels tested. No significant pretreatment elevation of plasma 2-HG was observed in glioma patients. The 500 mg QD dose resulted in the largest magnitude of 2-HG inhibition relative to other dose levels. The results were reported from 168 patients [5] [6] [4] .

Publications

  1. Agios Pharmaceuticals. Agios Presents Updated Phase 1 Data from Dose Expansion Cohort of Ivosidenib (AG-120) in Patients with IDH1 Mutant Positive Glioma. Media-Rel 2017;.

    Media Release
  2. Agios Pharmaceuticals. Agios Presents Phase 1 Data from Dose-Escalation and Expansion Cohorts of AG-120 (Ivosidenib) in Patients with Previously Treated IDH1 Mutant Positive Cholangiocarcinoma. Media-Rel 2017;.

    Media Release
  3. Agios Pharmaceuticals. Agios Announces Phase 1 Data from Dose Expansion Cohorts of AG-120 in Patients with IDH1 Mutant Positive Glioma and Chondrosarcoma. Media-Rel 2016;.

    Media Release
  4. Fan B, Mellinghoff IK, Wen PY, Pandya SS, Jiang L, Liu G, et al. Pharmacokinetics/pharmacodynamics (PK/PD) of ivosidenib in patients with IDH1-mutant advanced solid tumors from a phase 1 study. ASCO-2018 2018; abstr. 2577.

    Available from: URL: http://abstracts.asco.org/214/AbstView_214_211401.html
  5. Fan B, Goyal L, Lowery MA, Pandya SS, Manyak E, Le K, et al. Pharmacokinetic/pharmacodynamic (PK/PD) profile of AG-120 in patients with IDH1-mutant cholangiocarcinoma from a phase 1 study of advanced solid tumors. ASCO-2017 2017; abstr. 4082.

    Available from: URL: http://abstracts.asco.org/199/AbstView_199_182082.html
  6. Ishii Y, Sigel C, Lowery MA, Goyal L, Gliser C, Jiang L, et al. AG-120 (ivosidenib), a first-in-class mutant IDH1 inhibitor, promotes morphologic changes and upregulates liver-specific genes in IDH1 mutant cholangiocarcinoma. AACR-NCI-EORTC-2017 2017; abstr. A071 / 71.

    Available from: URL: http://link.adisinsight.com/y7AZe
  7. Aguado-Fraile E, Choe S, Gliser C, Steelman L, Jiang L, Fan B, et al. Detection of IDH1 mutations in plasma cell-free circulating tumor DNA (ctDNA) from patients with cholangiocarcinoma. AACR-2019 2019; abstr. 2275 / 4.

    Available from: URL: http://link.adisinsight.com/Fb49Q
  8. Lowery MA, Abou-Alfa GK, Burris HA, Janku F, Shroff RT, Cleary JM, et al. Phase I study of AG-120, an IDH1 mutant enzyme inhibitor: Results from the cholangiocarcinoma dose escalation and expansion cohorts. ASCO-2017 2017; abstr. 4015.

    Available from: URL: http://abstracts.asco.org/199/AbstView_199_180737.html
  9. Fan B, Mellinghoff IK, Wen PY, Lowery MA, Goyal L, Tap WD, et al. Clinical pharmacokinetics and pharmacodynamics of ivosidenib, an oral, targeted inhibitor of mutant IDH1, in patients with advanced solid tumors. Invest-New-Drugs 2019;.

    PubMed | CrossRef Fulltext
  10. Mellinghoff IK, Ellingson BM, Touat M, Maher E, De La Fuente MI, Holdhoff M, et al. Ivosidenib in Isocitrate Dehydrogenase 1-Mutated Advanced Glioma. . J-Clin-Oncol 2020;JCO1903327.

    PubMed | CrossRef Fulltext
  11. Tap WD, Villalobos VM, Cote GM, Burris H, Janku F, Mir O, et al. Phase I Study of the Mutant IDH1 Inhibitor Ivosidenib: Safety and Clinical Activity in Patients With Advanced Chondrosarcoma. J-Clin-Oncol 2020;JCO1902492.

    PubMed | CrossRef Fulltext
  12. Le K, Poland B, Dai D, Fan B, Liu H, Attar EC, et al. Relationship of Ivosidenib Plasma Concentration to Heart Rate- Corrected Qt Interval in Patients with Idh1-Mutant Advanced Hematologic Malignancies. ASCPT-2019 2019; abstr. PIII-011.

    Available from: URL: https://www.ascpt.org/Meetings/Annual-Meeting

Authors

Author Total Publications First Author Last Author
Abou-Alfa GK 1 - -
Agios Pharmaceuticals 3 3 3
Agresta S 2 - -
Agresta SV 2 - -
Aguado-Fraile E 1 1 -
Attar EC 1 - -
Auer J 2 - -
Azad NS 1 - -
Beeram M 2 - -
Bowden C 1 - -
Burris H 2 - -
Burris HA 1 - -
Choe S 4 - -
Cleary JM 1 - -
Cloughesy TF 1 - -
Cote GM 2 - -
Dai D 4 - 3
De La Fuente MI 1 - -
Deshpande V 1 - 1
Ellingson BM 1 - -
Fan B 7 3 -
Gliser C 5 - -
Gore L 1 - -
Goyal L 4 - -
Hickman D 1 - -
Holdhoff M 1 - -
Hollebecque A 1 - -
Huang R 1 - -
Ishii Y 2 1 -
Janku F 3 - -
Jiang L 8 - -
Le K 3 1 -
Liu G 2 - -
Liu H 1 - -
Lowery MA 5 1 -
Lu M 1 - -
Maher E 1 - -
Maher EA 1 - -
Manyak E 2 - -
Mellinghoff IK 3 1 -
Mir O 1 - -
Nimkar T 2 - -
Pandya S 2 - -
Pandya SS 6 - -
Poland B 1 - -
Prahl Judge M 1 - -
Shroff RT 1 - -
Sigel C 1 - -
Steelman L 2 - -
Tap WD 2 1 -
Touat M 1 - -
Trent JC 2 - 1
Villalobos VM 1 - -
Wagner AJ 1 - -
Wen PY 3 - 1
Wu B 3 - 1
Yang H 3 - 1
Yen K 2 - -
Young RJ 1 - -
Zhu AX 1 - 1

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Agresta S
Phone: 617.649.8621
sam.agresta@agios.com
show details
Agios Pharmaceuticals
-
Chris Korth
617.649.8278 chris.korth@agios.com
show details
-
Prahl M
Phone: 617.649.8635
molly.prahl@agios.com
show details
Agios Pharmaceuticals
-
Sam Agresta, MD, MPH & TM
617.649.8621 sam.agresta@agios.com
show details
-

Centres

Centre Name Location Trial Centre Country
-
-
-
- Aurora, Colorado USA
- Baltimore, Maryland USA
- Boston, Massachusetts USA
- Dallas, Texas USA
- Houston, Texas USA
- Los Angeles, California USA
- Miami, Florida USA
- Nashville, Tennessee USA
- New York, New York USA
- San Antonio, Texas USA
- Villejuif France
Agios Pharmaceuticals
-
-

Trial History

Event Date Event Type Comment
12 Jun 2020 Results Results (data cutoff date January 16, 2019; n=66) determining safety and tolerability of oral ivosidenib as a single agent in patients with glioma, published in the Journal of Clinical Oncology Updated 25 Jun 2020
30 Apr 2020 Other trial event Last checked against ClinicalTrials.gov record. Updated 30 Apr 2020
24 Mar 2020 Results Results (n=21) assessing safety and clinical activity in patients With advanced chondrosarcoma, published in the Journal of Clinical Oncology Updated 01 Apr 2020
26 Apr 2019 Results Results (n=168, data cut off: May 12, 2017) published in the Investigational New Drugs Updated 03 May 2019
03 Apr 2019 Results Results detecting IDH1 mutations in plasma cell-free circulating tumor DNA using plasma samples from AG120-C-002 and AG881-C-002 trials presented at the 110th Annual Meeting of the American Association for Cancer Research Updated 10 Apr 2019
16 Mar 2019 Results Pooled data from 3 studies (NCT02579707, NCT02074839 and NCT02073994) presented at the 120th Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics. Updated 07 May 2019
19 Jul 2018 Completion date Planned End Date changed from 1 Dec 2017 to 1 Jun 2021. Updated 26 Jul 2018
19 Jul 2018 Other trial event Planned primary completion date changed from 1 Dec 2017 to 1 Jun 2021. Updated 26 Jul 2018
05 Jun 2018 Results Results assessing Pharmacokinetics/pharmacodynamics (PK/PD) of ivosidenib presented at the 54th Annual Meeting of the American Society of Clinical Oncology Updated 25 Jun 2018
23 May 2018 Other trial event According to an Agios Pharmaceuticals media release, data will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2018. Updated 23 May 2018
12 Jan 2018 Completion date Planned End Date changed from 1 Aug 2017 to 1 Dec 2017. Updated 16 Jan 2018
12 Jan 2018 Other trial event Planned primary completion date changed from 1 Aug 2017 to 1 Dec 2017. Updated 16 Jan 2018
17 Nov 2017 Results Data (n=35) presented in an Agios Pharmaceuticals Media Release. Updated 24 Nov 2017
17 Nov 2017 Results According to an Agios Pharmaceuticals media release, updated data from glioma expansion cohort were presented at the Society for NeuroOncology Annual Meeting. Updated 24 Nov 2017
30 Oct 2017 Results Results of a gene expression analysis presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics 2017. Updated 31 Oct 2017
08 Aug 2017 Other trial event According to an Agios Pharmaceuticals media release, first data from the expansion phase will be presented at at the 2017 American Society of Hematology Annual Meeting and Exposition (ASH) in December. Updated 11 Aug 2017
08 Aug 2017 Other trial event According to an Agios Pharmaceuticals media release, updated data from glioma expansion cohort will be presented Society for NeuroOncology Annual Meeting in Nov 2017. Updated 11 Aug 2017
06 Jun 2017 Results Results (data cut off: 5 Dec, 2016; n=60) analysing pharmacokinetics and pharmacodynamics of AG-120 in patients with IDH1-mutant cholangiocarcinoma, presented at the 53rd Annual Meeting of the American Society of Clinical Oncology. Updated 22 Jun 2017
06 Jun 2017 Results Results (n=73;data cut off: 16 Dec 2016) assessing safety presented at the 53rd Annual Meeting of the American Society of Clinical Oncology. Updated 21 Jun 2017
03 Jun 2017 Results Results (n=73) from this trial published in an Agios Pharmaceuticals Media Release. Updated 08 Jun 2017
03 Jun 2017 Other trial event According to an Agios Pharmaceuticals media release, As of March 10, 2017, 73 patients with IDH1 mutant positive cholangiocarcinoma have been treated. Updated 08 Jun 2017
03 Jun 2017 Results According to an Agios Pharmaceuticals media release, updated data from the dose-escalation and expansion cohorts of this trial presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2017. Updated 08 Jun 2017
04 May 2017 Other trial event According to Agios Pharmaceuticals media release, first data from the cholangiocarcinoma expansion cohort from this trial will be available at ASCO 2017. Updated 24 May 2017
04 May 2017 Other trial event According to Agios Pharmaceuticals media release, first data from this study will be presented in H2 of 2017. Updated 11 May 2017
04 May 2017 Other trial event According to Agios Pharmaceuticals media release, enrollment of the 125-patient expansion cohort for this trial has been completed. Updated 11 May 2017
16 Feb 2017 Other trial event According to Agios Pharmaceuticals media release, first data from this study will be presented in H1 of 2017. Updated 18 Feb 2017
23 Nov 2016 Other trial event Planned number of patients changed from 145 to 170. Updated 28 Nov 2016
23 Nov 2016 Status change - active, no longer recruiting Status changed from recruiting to active, no longer recruiting. Updated 28 Nov 2016
18 Nov 2016 Results Results in patients with glioma and chondrosarcoma published in an Agios Pharmaceuticals media release. Updated 30 Nov 2016
18 Nov 2016 Other trial event First data from the expansion phase of this trial in chondrosarcoma patients were presented at the 2016 annual meeting of the Connective Tissue Oncology Society (CTOS), according to an Agios Pharmaceuticals media release. Updated 30 Nov 2016
18 Nov 2016 Results Data from dose expansion cohort in glioma patients presented at the Society for Neuro-Oncology (SNO) Annual Meeting 2016, according to an Agios Pharmaceuticals media release. Updated 30 Nov 2016
03 Nov 2016 Other trial event Preliminary data from the expansion phase of this trial in patietns with low-grade glioma will be presented at the Society for NeuroOncology (SNO) Annual Meeting 2016, according to an Agios Pharmaceuticals media release. Updated 15 Nov 2016
03 Nov 2016 Other trial event First data from the expansion phase of this trial in chondrosarcoma patients will be presented at the Connective Tissue Oncology Society (CTOS) Annual Meeting 2016, according to an Agios Pharmaceuticals media release. Updated 15 Nov 2016
12 Jul 2016 Completion date Planned End Date changed from 1 May 2016 to 1 Aug 2017. Updated 15 Jul 2016
12 Jul 2016 Other trial event Planned primary completion date changed from 1 May 2016 to 1 Aug 2017. Updated 15 Jul 2016
05 May 2016 Other trial event According to an Agios Pharmaceuticals media release, data from the expansion phase in advanced IDH1 mutant positive low-grade glioma is expected in the second half of 2016. Updated 12 May 2016
21 Jan 2015 Other trial event Planned number of patients changed from 51 to 145 as reported by ClinicalTrials.gov Updated 29 Jan 2015
21 Jan 2015 Completion date Planned End Date changed from 1 Mar 2016 to 1 May 2016 as reported by ClinicalTrials.gov Updated 29 Jan 2015
21 Jan 2015 Other trial event Planned primary completion date changed from 1 Mar 2016 to 1 May 2016 as repored by ClinicalTrials.gov Updated 29 Jan 2015
05 May 2014 Other trial event New source identified and integrated (Memorial Sloan-Kettering Cancer Center). Updated 03 Jun 2014
24 Mar 2014 Other trial event The first patient has been treated in this trial, according to an Agios Pharmaceuticals media release. Updated 26 Mar 2014
07 Mar 2014 New trial record New trial record Updated 07 Mar 2014

References

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