Study of APVO436 in Elderly or Unfit Patients With Newly Diagnosed AML

NCT04973618 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: 5002
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this Phase IB study is to evaluate the safety and tolerability of APVO436 in naïve elderly unfit patients with newly diagnosed primary AML at the RP2D level when it is used as an adjunct to the standard of care and obtain a preliminary assessment of the anti-leukemia activity of an APVO436-containing combination therapy. Study Objectives: \- Primary Objective: Evaluate the safety and tolerability of APVO436 at the RP2D level when it is used as an adjunct to the standard of care (venetoclax and azacitidine). \- Secondary Objectives:

• Obtain a preliminary assessment of the anti-leukemia activity of APVO436-containing experimental triple drug combination therapy modalities.
• Determine pharmacodynamics (PD) of APVO436, including changes in CD123 antigen density and measures of T cell number and function over time.
• Determine correlations between response and MRD level and cytogenetic and molecular genetic profiles.

Conditions

AML

Keywords

APVO436

Outcome Measures

Primary Outcomes (1)

• Safety - Incidence of Grade 3-4 AEs and SAEs

  The cumulative incidence of Grade 3-4 AEs, and SAEs, and the incidence of AES of interest (≥Grade 2 CRS, ≥Grade 2 Infusion related reaction, ≥2 cardiac toxicity and ≥2 neurotoxicity as complications of CRS) for safety

  during first 28 to 35 days of treatment

Secondary Outcomes (6)

• Efficacy - Incidence of composite CR (CR + CRi + CRh)

  Patient will have assessment at the end of each Cycle (each Cycle is 28 days) up to 6 months

• Efficacy - Incidence of HSCT

  Patient will have assessment after 1 year

• Exploratory - LFS rate

  up to 6 months

• Exploratory - 1-year LFS rate

  1 year

• Exploratory - 2-year LFS rate

  2 year

Study Arms (1)

APVO436

EXPERIMENTAL

CD123 and CD3 epsilon bispecific antibody

Biological: APVO436

Interventions

APVO436 BIOLOGICAL

APVO436 Dosage: APVO436 will be administered at a fixed dosage of 18 mcg after a weekly ramp up during Cycle 1 (Step-up dosing: C1D15: 6 mcg over 22 hours, C1D22: 12 mcg over 8 hours, C2D1: 18 mcg over 6 hours, C2D8: 18 mcg over 4 hours), totaling 18 µg in Cycle 1 and 72 µg/cycle for Cycles 2-4 for a total of 234 µg for the projected 4-cycle treatment course. Dosage Form: IV Solutions for Intravenous Administration Frequency: Weekly

APVO436

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals eligible to participate in this study must meet all of the following:
• All patients must meet the following criteria prior to the first dose of study drug:
• Signed informed consent. Consent must be obtained prior to any study-related procedure.
• Age ≥60 years
• Histologically confirmed AML: Subjects must have de novo (primary) or secondary AML (any WHO 2016 classification excluding acute promyelocytic leukemia) who have either comorbidities and/or advanced age (≥ 75 years) that preclude use of intensive induction chemotherapy as determined by the investigator.
• Patients must be therapy-naïve (newly diagnosed)
• Patients must have CD123-positive AML as confirmed by centralized flow cytometry (or immunohistochemistry \[IHC\]).
• Patients with precedent MDS are eligible
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
• Patients with previously untreated AML (by the World Health Organization (WHO) criteria, i.e. \>/= 20% blasts). Prior biologic therapies (such as growth factors) and targeted therapies administered for the treatment of prior myelodysplastic syndrome are allowed (such as lenalidomide or luspatercept), with the exception of hypomethylating agents 5-azacytidine or decitabine. Patients must have been off such therapy for 1 week prior to entering this study and recovered from the toxic effects of that therapy, unless there is evidence of rapidly progressive disease. Hydroxyurea is permitted for control of counts prior to treatment.
• Life expectancy of \> 2 months in the Investigator's opinion
• Creatinine ≤ 2.5 × upper limit of normal (ULN)
• Adequate liver test parameters: total bilirubin \< 2.5 × ULN (if disease related or secondary to Gilbert's disease, then total bilirubin \< 3.5 mg/dL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) \< 5 × ULN
• Prothrombin time (PT) / international normalized ratio (INR) and partial thromboplastin time (PTT) \< 2 × ULN
• Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) may participate, provided they meet the following conditions:

You may not qualify if:

• Subjects with any of the following will not be eligible for study participation:
• Acute promyelocytic leukemia (APL) with t(15;17) translocation
• Absolute peripheral blood myeloblast count greater than 20,000/mm3 - may receive hydroxyurea to reduce and control the myeloblast count down prior to and during the first week of the first cycle of treatment with study drug if necessary if deemed medically necessary and appropriate by the treating physician
• Patients with active central nervous system (CNS) involvement by AML will be excluded. A lumbar puncture does not need to be performed unless there is clinical suspicion of CNS involvement per investigator judgement. Concurrent therapy for CNS prophylaxis or continuation of therapy for controlled CNS AML is allowed with the approval of the sponsor.
• History of seizures
• Prior solid organ transplant is acceptable provided the patient is on no immunosuppressive therapy.
• Any therapy or experimental treatment for AML within 7 days of the first dose of study drug. The use of hydroxyurea is acceptable and does not exclude the patient.
• Active, uncontrolled infection requiring systemic therapy. If the infection is controlled or has resolved, maintenance and/or prophylactic systemic antimicrobials are permitted.
• Major surgery within 3 weeks prior to first dose of study drug
• Known to be positive for HIV, hepatitis B virus surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV)
• Uncontrolled hypertension, defined as blood pressure ≥ 140/90 mm Hg despite maximum medical intervention
• History of congenital long QT syndrome or torsades de pointes
• Pathologic bradycardia or heart block (excluding first degree heart block)
• Prolonged baseline QTc, defined as QTcF (Fredericia correction) interval \>480 msec (other correction formulas may be used for patients with bundle branch block or ventricular pacemaker)
• History of ventricular arrhythmia (excluding PVCs)

Sponsors & Collaborators

• Aptevo Therapeutics: lead

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: APVO436 will be administered at a fixed dosage of 18 mcg after a weekly ramp up during Cycle 1 (Step-up dosing: C1D15: 6 mcg over 22 hours, C1D22: 12 mcg over 8 hours, C2D1: 18 mcg over 6 hours, C2D8: 18 mcg over 4 hours), totaling 18 µg in Cycle 1 and 72 µg/cycle for Cycles 2-4 for a total of 234 µg for the projected 4-cycle treatment course.

Study Record Dates

• First Submitted: July 12, 2021
• First Posted: July 22, 2021
• Study Start: January 1, 2025
• Primary Completion: January 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: December 1, 2021

Record last verified: 2021-11