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

Forma Therapeutics

Status and phase: Completed; Phase 2; Phase 1

Conditions: Acute Myelogenous Leukemia; Myelodysplastic Syndrome; Acute Myeloid Leukemia

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02719574

2102-HEM-101

Details and patient eligibility

About

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.

Enrollment: 336 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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336 participants in 11 patient groups

PH1 Dose Escalation & Expansion FT-2102 (olutasidenib)

Experimental group

Treatment:

Drug: FT-2102 (olutasidenib)

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

Experimental group

Treatment:

Drug: Azacitidine

Drug: FT-2102 (olutasidenib)

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

Experimental group

Treatment:

Drug: FT-2102 (olutasidenib)

Drug: Cytarabine

PH2 Cohort 1 FT-2102 (olutasidenib) Single Agent

Experimental group

Description:

Relapsed or Refractory (R/R) AML

Treatment:

Drug: FT-2102 (olutasidenib)

PH2 Cohort 2 FT-2102 (olutasidenib) Single Agent

Experimental group

Description:

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

Treatment:

Drug: FT-2102 (olutasidenib)

PH2 Cohort 3 FT-2102 (olutasidenib) Single Agent

Experimental group

Description:

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

Treatment:

Drug: FT-2102 (olutasidenib)

PH2 Cohort 4 FT-2102 (olutasidenib)+Azacitidine

Experimental group

Description:

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

Treatment:

Drug: Azacitidine

Drug: FT-2102 (olutasidenib)

PH2 Cohort 5 FT-2102 (olutasidenib)+Azacitidine

Experimental group

Description:

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

Treatment:

Drug: Azacitidine

Drug: FT-2102 (olutasidenib)

PH2 Cohort 6 FT-2102 (olutasidenib)+Azacitidine

Experimental group

Description:

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

Treatment:

Drug: Azacitidine

Drug: FT-2102 (olutasidenib)

PH2 Cohort 7 FT-2102 (olutasidenib) Single Agent

Experimental group

Description:

Treatment naïve AML for whom standard treatments are contraindicated

Treatment:

Drug: FT-2102 (olutasidenib)

PH2 Cohort 8 FT-2102 (olutasidenib)+Azacitidine

Experimental group

Description:

Treatment naïve AML who are candidates for azacitidine first line treatment

Treatment:

Drug: Azacitidine

Drug: FT-2102 (olutasidenib)