A Phase 1, Multicenter, Open-Label, Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Orally Administered FHD-286, as Monotherapy or Combination Therapy, in Subjects With Advanced Hematologic Malignancies
Overview
- Phase
- Phase 1
- Intervention
- FHD-286
- Conditions
- Advanced Hematologic Malignancy
- Sponsor
- Foghorn Therapeutics Inc.
- Enrollment
- 144
- Locations
- 5
- Primary Endpoint
- Incidence of AEs, dose-limiting toxicities (DLTs), serious AEs (SAEs), AEs leading to discontinuation, and adverse events of special interest (AESIs); safety laboratory assessments
- Status
- Active, not recruiting
- Last Updated
- 9 months ago
Overview
Brief Summary
This Phase 1, multicenter, open-label, dose escalation study is designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of FHD-286 administered orally as monotherapy or combination therapy, in subjects with advanced hematologic malignancies.
Detailed Description
This study is primarily intended to evaluate the safety and tolerability of FHD-286 when administered orally as monotherapy or in combination with either LDAC or decitabine to subjects with R/R AML, R/R MDS, and R/R CMML not in blast crisis. In each arm of the study, successive cohorts of participants will receive increasing oral doses of FHD-286 as a single agent or in combination with LDAC or decitabine to determine the RP2D(s) in this population. The data from this study in subjects with advanced hematologic malignancies, including safety, tolerability, PK/PD findings, and antitumor activity, will form the basis for subsequent clinical development of FHD-286.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject must be ≥16 years of age.
- •Subject must:
- •Have a confirmed diagnosis of R/R AML, R/R MDS, or R/R CMML not in blast crisis AND
- •Have received ≤4 prior lines of systemic anticancer therapy for their disease under study; subjects who have received \>4 prior lines of systemic anticancer therapy for their disease under study must receive Sponsor approval. AND
- •Be an appropriate candidate for treatment with LDAC (Arm A) or decitabine (Arm B)
- •Subject or their parent or legal guardian (when applicable) must be able to understand and be willing to sign an informed consent and, when applicable, subject must sign an assent form.
- •Subject must be willing and able to comply with scheduled study visits and treatment plans.
- •Subject must be willing to undergo all study procedures unless contraindicated due to medical risk.
- •Subject must have an ECOG PS of ≤
- •Subject must have a life expectancy of ≥3 months.
Exclusion Criteria
- •Subject is unable to provide informed consent and/or to follow protocol requirements.
- •Has undergone chimeric antigen receptor T cell therapy or HSCT within 60 days of the first dose of study treatment OR
- •Has clinically significant GVHD
- •Subject has evidence (or suspicion) of extramedullary involvement, unless approved by Sponsor.
- •Subject has an immediately life-threatening, severe complication(s) of advanced myeloid malignancy, such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.
- •Subject has other malignancy that may interfere with the diagnosis and/or treatment of advanced hematologic malignancies.
- •Subject has active HBV or HCV infections; Subject has known positive HIV antibody results, or AIDS-related illness.
- •Subject has an active severe infection that requires anti-infective therapy or has an unexplained temperature of \>38.5°C during screening visits or on their first day of study treatment.
- •Subject has an uncontrolled intercurrent illness.
- •Subject has QTcF \>470 msec or other factors that increase the risk of QTc prolongation or arrhythmic events.
Arms & Interventions
FHD-286 in Combination with Decitabine
FHD-286 administered orally + decitabine administered intravenously (IV)
Intervention: FHD-286
FHD-286 Monotherapy
Closed to Enrollment
Intervention: FHD-286
FHD-286 in Combination with LDAC
FHD-286 administered orally + LDAC administered subcutaneously
Intervention: FHD-286
FHD-286 in Combination with LDAC
FHD-286 administered orally + LDAC administered subcutaneously
Intervention: Low Dose Cytarabine
FHD-286 in Combination with Decitabine
FHD-286 administered orally + decitabine administered intravenously (IV)
Intervention: Decitabine
Outcomes
Primary Outcomes
Incidence of AEs, dose-limiting toxicities (DLTs), serious AEs (SAEs), AEs leading to discontinuation, and adverse events of special interest (AESIs); safety laboratory assessments
Time Frame: Up to 18 months
Secondary Outcomes
- AML: Duration of CR + CRh(Up 18 months)
- AML: Transfusion independence rate(Up 18 months)
- MDS & CMML: Hematologic Improvement rate(Up to 18 months)
- AML: Event free survival (EFS)(Up 42 months)
- AML: Duration of CR(Up 18 months)
- AML: CR + CR with partial hematologic recovery (CRh) rate(Up 18 months)
- MDS & CMML: Duration of CR(Up to 18 months)
- MDS & CMML: Duration of PR(Up to 18 months)
- MDS & CMML: CR + PR(Up to 18 months)
- MDS & CMML: Duration of CR + PR(Up to 18 months)
- AML: Complete remission (CR) rate(Up to 18 months)
- AML: Overall survival (OS)(Up to 42 months)
- MDS: CR rate(Up to 18 months)
- MDS & CMML: Partial remission (PR) rate(Up to 18 months)
- MDS & CMML: EFS(Up to 42 months)
- MDS: OS(Up to 42 months)
- PK parameter: Area under the plasma concentration time curve (AUC)(Day 1 and day 8 of cycle 1 (each cycle is 28 days))
- Plasma concentration vs. time profiles(Day 1 and day 8 of cycle 1 (each cycle is 28 days))