Open-label Study of FT-2102 With or Without Azacitidine or Cytarabine in Patients With AML or MDS With an IDH1 Mutation

NCT02719574 | Completed Phase 1 Results

• 1 other identifier: 2102-HEM-101
• Study Type: interventional
• Target: 336
• Locations: 9 countries
• Sites: 60

Brief Summary

This Phase 1/2 study will evaluate the safety, efficacy, PK, and PD of FT-2102 (olutasidenib) as a single agent or in combination with azacitidine or cytarabine. The Phase 1 stage of the study is split into 2 distinct parts: a dose escalation part, which will utilize an open-label design of FT-2102 (olutasidenib) (single agent) and FT-2102 (olutasidenib) + azacitidine (combination agent) administered via one or more intermittent dosing schedules followed by a dose expansion part. The dose expansion part will enroll patients in up to 5 expansion cohorts, exploring single-agent FT-2102 (olutasidenib) activity as well as combination activity with azacitidine or cytarabine. Following the completion of the relevant Phase 1 cohorts, Phase 2 will begin enrollment. Patients will be enrolled across 8 different cohorts, examining the effect of FT-2102 (olutasidenib) (as a single agent) and FT-2102 (olutasidenib) + azacitidine (combination) on various AML/MDS disease states.

Conditions

Acute Myeloid Leukemia; Acute Myelogenous Leukemia; Myelodysplastic Syndrome

Keywords

AML; MDS; IDH1; IDH

Outcome Measures

Primary Outcomes (7)

• Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  A TEAE was defined as an adverse event (AE) that emerges during treatment, having been absent pre-treatment, or worsens relative to the pre-treatment state. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, or is life-threatening, or requires inpatient hospitalization or causes prolongation of existing hospitalization results in persistent or significant disability/incapacity, or may have caused a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. Number of participants with TEAEs and SAEs is reported. Safety analysis set (SAS) included all the participants who have received at least one dose of study drug (FT-2102, azacitidine, or cytarabine).

  Phase 1: From start of drug administration (Day 1) up to 28 days after last dose of study drug (up to 82 months)

• Phase 1: Number of Participants With Change From Baseline in Clinically Significant Abnormal Laboratory Values

  Number of participants with change from baseline in clinically significant abnormal laboratory values for hematology, chemistry and coagulation with Grade \<1 to 4 is reported. National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 toxicity grade used to determine severity of AE. Grade 1: mild;asymptomatic/mild symptoms; Grade 2: moderate; minimal; Grade 3: severe/medically significant; Grade 4: life-threatening consequences, Grade 5: death.

  Phase 1: From Baseline up to 28 days after last dose of study drug (up to 82 months)

• Phase 1: Number of Participants With Change From Baseline in Clinically Significant Abnormal Electrocardiogram (ECG)

  Number of participants with change from baseline in clinically significant abnormal ECG parameter (QTcF) is reported. QT interval was the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF was the QT interval corrected for heart rate using Fridericia's formula: QTcF = QT divided by cube root of 60/heart rate.

  Phase 1: From Baseline up to 28 days after last dose of study drug (up to 82 months)

• Phase 2, Cohort 1: Percentage of Participants With Complete Remission (CR) Plus Complete Remission With Partial Hematological Recovery (CRh) for Acute Myeloid Leukemia Assessed by Investigator Based on International Working Group (IWG) Response Criteria

  Percentage of participants with CR plus CRh (CR, Molecular CR \[CRm\], Cytogenetic CR \[CRc\], CRh) is re-ported. CR is defined as bone marrow blasts less than (\<) 5 percent (%) (in aspirate with spicules and 200 nucleated cells), no blasts with auer rods, no extramedullary disease, absolute neutrophil count (ANC) greater than or equal to (\>=) 1000/μL, platelet count \>=100,000/μL and transfusion independ-ence. CRc is defined as CR with no residual cytogenetic abnormalities. CRm is defined as CR with unde-tectable IDH1m minimal residual disease (MRD) and CRh is defined as bone marrow blasts and partial recovery of peripheral blood counts (platelet count \>50 × 10\^9/L and ANC \> 0.5 × 10\^9/L).

  Phase 2: up to 3 weeks post last dose of study drug or until the introduction of new anticancer therapy, whichever is earlier (up to 82 months)

• Phase 2, Cohort 3, 4, 5, 6, 7, 8: Percentage of Participants With CR Plus CRh for Acute Myeloid Leukemia Assessed by Investigator Based on IWG Response Criteria

  Percentage of participants with CR plus CRh (CR, Molecular CR \[CRm\]), Cytogenetic CR \[CRc\], CRh) is re-ported. CR is defined as bone marrow blasts \<5 % (in aspirate with spicules and 200 nucleated cells), no blasts with auer rods, no extramedullary disease, ANC \>=1000/μL, platelet count \>=100,000/μL and transfusion independ-ence. CRc is defined as CR with no residual cytogenetic abnormalities. CRm is de-fined as CR with undetectable IDH1m MRD and CRh is defined as bone marrow blasts and partial recovery of peripheral blood counts (platelet count \>50 × 10\^9/L and ANC \> 0.5 × 10\^9/L).

  Phase 2: up to 3 weeks post last dose of study drug or until the introduction of new anticancer therapy, whichever is earlier (up to 82 months)

• Phase 2, Cohort 4 and 5: Percentage of Participants With CR for MDS Assessed by IWG Response Criteria

  Percentage of participants with complete remission (CR) is reported. CR is defined as bone marrow blast ≤ 5% myeloblasts with normal maturation of all cell lines, peripheral blood: Hgb ≥11 grams per deciliter (g/dL), platelets ≥ 100 × 10\^9/L, neutrophils ≥ 1.0 × 10\^9/L and blasts 0%.

  Phase 2: up to 3 weeks post last dose of study drug or until the introduction of new anticancer therapy, whichever is earlier (up to 82 months)

• Phase 2, Cohort 2: Four-month Relapse Free Survival (RFS) Rate

  RFS is defined as the time between the date of first dose until relapse or death from any cause, whichever occurs first. RFS is calculated for all participants in Phase 2 Cohort 2. 4-Month RFS rate is defined as the percentage of participants in Phase 2 Cohort 2 who have not relapsed or died on or before their 4-month response evaluation.

  Phase 2: From the date of first dose until relapse or death from any cause, whichever occurs first (up to 4 months)

Secondary Outcomes (20)

• Phase 1: Area Under the Curve (AUClast) for FT-2102

  Phase 1: Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle length= 28 days)

• Phase 1: Maximum Plasma Concentration (Cmax) for FT-2102

  Phase 1: Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle length= 28 days)

• Phase 1: Time to Maximum Plasma Concentration (Tmax) for FT-2102

  Phase 1: Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle length= 28 days)

• Phase 1: Time to Response (TTR) for AML

  Phase 1: Time from first dose of study drug until documentation of the first overall response (up to 82 months)

• Phase 1: Duration of Overall Response for AML

  Phase 1: From date of the first response to the date of the relapse or death (up to 82 months)

Study Arms (11)

PH1 Dose Escalation & Expansion FT-2102 (olutasidenib)

EXPERIMENTAL

Drug: FT-2102 (olutasidenib)

PH1 Esc. and Exp. FT-2102 (olutasidenib)+Azacitidine

EXPERIMENTAL

Drug: FT-2102 (olutasidenib); Drug: Azacitidine

PH1 Esc. and Exp. FT-2102 (olutasidenib)+Cytarabine

EXPERIMENTAL

Drug: FT-2102 (olutasidenib); Drug: Cytarabine

PH2 Cohort 1 FT-2102 (olutasidenib) Single Agent

EXPERIMENTAL

Relapsed or Refractory (R/R) AML

Drug: FT-2102 (olutasidenib)

PH2 Cohort 2 FT-2102 (olutasidenib) Single Agent

EXPERIMENTAL

AML in morphologic complete remission or complete remission with incomplete blood count recovery (CR/CRi) after prior therapy with residual IDH1-R132 mutation

Drug: FT-2102 (olutasidenib)

PH2 Cohort 3 FT-2102 (olutasidenib) Single Agent

EXPERIMENTAL

R/R AML/MDS, previously treated with FT-2102

Drug: FT-2102 (olutasidenib)

PH2 Cohort 4 FT-2102 (olutasidenib)+Azacitidine

EXPERIMENTAL

R/R AML/MDS that are naïve to prior hypomethylating therapy and IDH1 inhibitor therapy

Drug: FT-2102 (olutasidenib); Drug: Azacitidine

PH2 Cohort 5 FT-2102 (olutasidenib)+Azacitidine

EXPERIMENTAL

R/R AML/MDS that have inadequately responded to or have progressed on prior hypomethylating therapy

Drug: FT-2102 (olutasidenib); Drug: Azacitidine

PH2 Cohort 6 FT-2102 (olutasidenib)+Azacitidine

EXPERIMENTAL

R/R AML/MDS that have been previously treated with single-agent FT-2102 as their last therapy prior to study enrollment

Drug: FT-2102 (olutasidenib); Drug: Azacitidine

PH2 Cohort 7 FT-2102 (olutasidenib) Single Agent

EXPERIMENTAL

Treatment naïve AML for whom standard treatments are contraindicated

Drug: FT-2102 (olutasidenib)

PH2 Cohort 8 FT-2102 (olutasidenib)+Azacitidine

EXPERIMENTAL

Treatment naïve AML who are candidates for azacitidine first line treatment

Drug: FT-2102 (olutasidenib); Drug: Azacitidine

Interventions

FT-2102 (olutasidenib) DRUG

FT-2102 (olutasidenib) will be supplied as 50 mg or 150 mg capsules and will be administered per the protocol defined frequency and dose level

PH1 Dose Escalation & Expansion FT-2102 (olutasidenib); PH1 Esc. and Exp. FT-2102 (olutasidenib)+Azacitidine; PH1 Esc. and Exp. FT-2102 (olutasidenib)+Cytarabine; PH2 Cohort 1 FT-2102 (olutasidenib) Single Agent; PH2 Cohort 2 FT-2102 (olutasidenib) Single Agent; PH2 Cohort 3 FT-2102 (olutasidenib) Single Agent; PH2 Cohort 4 FT-2102 (olutasidenib)+Azacitidine; PH2 Cohort 5 FT-2102 (olutasidenib)+Azacitidine; PH2 Cohort 6 FT-2102 (olutasidenib)+Azacitidine; PH2 Cohort 7 FT-2102 (olutasidenib) Single Agent; PH2 Cohort 8 FT-2102 (olutasidenib)+Azacitidine

Azacitidine DRUG

azacitidine will be administered per site's standard of care

Also known as: Vidaza

PH1 Esc. and Exp. FT-2102 (olutasidenib)+Azacitidine; PH2 Cohort 4 FT-2102 (olutasidenib)+Azacitidine; PH2 Cohort 5 FT-2102 (olutasidenib)+Azacitidine; PH2 Cohort 6 FT-2102 (olutasidenib)+Azacitidine; PH2 Cohort 8 FT-2102 (olutasidenib)+Azacitidine

Cytarabine DRUG

low-dose cytarabine will be administered per site's standard of care

PH1 Esc. and Exp. FT-2102 (olutasidenib)+Cytarabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically proven acute myeloid leukemia (AML) (except acute promyelocytic leukemia \[APL\] with the t(15;17) translocation) or intermediate, high-risk, or very high risk Myelodysplastic Syndrome (MDS) as defined by the World Health Organization (WHO) criteria or Revised International Prognostic Scoring System (IPSS-R) which is relapsed or refractory (R/R) to standard therapy and/or for which standard therapy is contraindicated or which has not adequately responded to standard therapy.
• Patients must have documented IDH1-R132 gene-mutated disease as evaluated by the site
• Good performance status
• Good kidney and liver function

You may not qualify if:

• Patients with symptomatic central nervous system (CNS) metastases or other tumor location (such as spinal cord compression, other compressive mass, uncontrolled painful lesion, bone fracture, etc.) necessitating an urgent therapeutic intervention, palliative care, surgery or radiation therapy
• Congestive heart failure (New York Heart Association Class III or IV) or unstable angina pectoris. Previous history of myocardial infarction within 1 year prior to study entry, uncontrolled hypertension or uncontrolled arrhythmias
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy

Sponsors & Collaborators

• Forma Therapeutics, Inc.: lead

Study Sites (60)

UCLA Medical Center

Los Angeles, California, 90024, United States

Location

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Yale University

New Haven, Connecticut, 06510, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Emory Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

New York Medical College

Hawthorne, New York, 10532, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Cornell University Weill Medical College

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University

Portland, Oregon, 97229, United States

Location

Sarah Cannon Research Institute - Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Victoria Cancer Care Center

Parkville, Victoria, 3000, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Box Hill Hospital, Monash University and Eastern Health Clinical School

Box Hill, 3128, Australia

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Service d'Hématologie Clinique, Hôpital Avicenne-APHP-Université Paris

Bobigny, 93000, France

Location

Assistance Publique Hopitaux de Marseille (AP-HM) - Hopital Nord

Marseille, 13005, France

Location

Centre Hospitalier Universitaire Nantes

Nantes, 44093, France

Location

Hôpital Saint-Louis

Paris, 75010, France

Location

Hopitaux Universitaires Est Parisien Hopital Saint-Antoine

Paris, 75012, France

Location

Centre Hospitalier Universitaire (CHU) Bordeaux - Hospitaux du Haut Leveque

Pessac, 33604, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

University Hospital of Rennes

Rennes, 35033, France

Location

Institut Universitaire du Cancer Toulouse - Oncopole

Toulouse, 31059, France

Location

Centre Hospitalier Universitaire de Nancy - Hopital Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Institut de Cancérologie Gustave Roussy

Villejuif, 94805, France

Location

Staedtisches Klinikum Braunschweig gGmbH

Braunschweig, Germany

Location

Universitaetsklinikum Giessen und Marburg GmbH - Klinik fuer Innere Medizin

Giessen, Germany

Location

Landeszentrum fuer Zell- und Gentherapie

Halle, Germany

Location

Universitätsklinikum Münster Medizinische Klinik A, Hämatologie, Hämostaseologi

Münster, Germany

Location

AOU S. Luigi Gonzaga - Orbassano

Orbassano, Turin, Italy

Location

Ospedale Mazzoni - UOC Ematologia Ascoli Piceno

Ascoli Piceno, Italy

Location

Universita di Bologna

Bologna, Italy

Location

Dipartimento di Oncologia Medica - IRST IRCC

Meldola, Italy

Location

Università degli Studi di Parma

Parma, Italy

Location

U.O. Ematologia Ravenna

Ravenna, Italy

Location

Hospital Rimini Hematology, Department of Oncology and Hematoloy

Rimini, Italy

Location

Seoul National University Bundang Hospital

Gumi, 13620, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 8036, Spain

Location

Institut Català d'Oncologia-Hospital Duran i Reynals

Barcelona, 8908, Spain

Location

Hospital Universitario 12 De Octubre

Madrid, 28041, Spain

Location

Hospital Clínico Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital La Fe

Valencia, 46026, Spain

Location

University College London Hospitals NHS Foundation Trust

London, NW1 2PG, United Kingdom

Location

St. George's University Hospital

London, United Kingdom

Location

Churchill Hospital

Oxford, United Kingdom

Location

Southampton General Hospital

Southampton, United Kingdom

Location

Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (5)

• Cortes J, Curti A, Fenaux P, Jonas BA, Krauter J, Montesinos P, Recher C, Taussig DC, Wang ES, Watts J, Wei A, Yee KW, Tian H, Sheppard A, Marzac C, de Botton S. Olutasidenib for mutated IDH1 acute myeloid leukemia: final five-year results from the phase 2 pivotal cohort. J Hematol Oncol. 2025 Nov 14;18(1):102. doi: 10.1186/s13045-025-01751-w.

  PMID: 41239466 DERIVED

• Cortes JE, Yang J, Roboz GJ, Dinner SN, Wang ES, Wei AH, Tian H, di Trapani F, Baer MR, Donnellan W, Watts JM. Olutasidenib alone or combined with azacitidine in patients with mutant IDH1 myelodysplastic syndrome. Blood Adv. 2025 Oct 28;9(20):5293-5305. doi: 10.1182/bloodadvances.2025016718.

  PMID: 40668616 DERIVED

• Cortes JE, Roboz GJ, Baer MR, Jonas BA, Schiller GJ, Yee K, Ferrell PB, Yang J, Wang ES, Blum WG, Mims A, Tian H, Sheppard A, de Botton S, Montesinos P, Curti A, Watts JM; Olutasidenib Combination Therapy Study Group. Olutasidenib in combination with azacitidine induces durable complete remissions in patients with relapsed or refractory mIDH1 acute myeloid leukemia: a multicohort open-label phase 1/2 trial. J Hematol Oncol. 2025 Jan 16;18(1):7. doi: 10.1186/s13045-024-01657-z.

  PMID: 39819505 DERIVED

• de Botton S, Fenaux P, Yee K, Recher C, Wei AH, Montesinos P, Taussig DC, Pigneux A, Braun T, Curti A, Grove C, Jonas BA, Khwaja A, Legrand O, Peterlin P, Arnan M, Blum W, Cilloni D, Hiwase DK, Jurcic JG, Krauter J, Thomas X, Watts JM, Yang J, Polyanskaya O, Brevard J, Sweeney J, Barrett E, Cortes J. Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML. Blood Adv. 2023 Jul 11;7(13):3117-3127. doi: 10.1182/bloodadvances.2022009411.

  PMID: 36724515 DERIVED

• Watts JM, Baer MR, Yang J, Prebet T, Lee S, Schiller GJ, Dinner SN, Pigneux A, Montesinos P, Wang ES, Seiter KP, Wei AH, De Botton S, Arnan M, Donnellan W, Schwarer AP, Recher C, Jonas BA, Ferrell PB Jr, Marzac C, Kelly P, Sweeney J, Forsyth S, Guichard SM, Brevard J, Henrick P, Mohamed H, Cortes JE. Olutasidenib alone or with azacitidine in IDH1-mutated acute myeloid leukaemia and myelodysplastic syndrome: phase 1 results of a phase 1/2 trial. Lancet Haematol. 2023 Jan;10(1):e46-e58. doi: 10.1016/S2352-3026(22)00292-7. Epub 2022 Nov 10.

  PMID: 36370742 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

olutasidenib; Azacitidine; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Arabinonucleosides

Results Point of Contact

• Title: Clinical Reporting Anchor and Disclosure (1452)
• Organization: Novo Nordisk A/S

clinicaltrials@novonordisk.com

(+1) 866-867-7178

Study Officials

• Clinical Transparency (dept. 2834)

  Novo Nordisk A/S

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2016
• First Posted: March 25, 2016
• Study Start: April 30, 2016
• Primary Completion: December 28, 2023
• Study Completion: January 24, 2024
• Last Updated: June 26, 2025
• Results First Posted: June 26, 2025

Record last verified: 2025-06

Locations

KR (2); ES (6); US (19); DE (4); CA (1); IT (7); GB (5); FR (11); AU (5)