Study of APVO436 in Patients With AML or MDS

NCT03647800 | Unknown Phase 1 FDA Drug

• 1 other identifier: Protocol 5001
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 12

Brief Summary

The primary objective of the Phase 1 part of the study is to determine the recommended dose of APVO436 administered intravenously to patients with AML or MDS. The primary objective of the Phase 1b part of the study is to evaluate the clinical activity of APVO436 in patients with AML or MDS. APVO436 is being studied in this Phase 1b, open-label, multi-center, two-part dose-escalation/dose expansion study to evaluate the safety, pharmacokinetic/pharmacodynamic (PK/PD), and clinical activity of APVO436 in patients with AML and MDS. The study will be conducted in 2 parts. The first part of this Phase 1B study is an open-label, multiple dose ascending dose escalation phase to determine the recommended dose (RP2D) level of APVO436 for future Phase 2 studies. The goal of the dose expansion phase of the study (Part 2) is to (i) evaluate the safety and tolerability of APVO436 at the RP2D level when it is used as an adjunct to the standard of care and (ii) obtain a preliminary assessment of the anti-leukemia activity of APVO436-containing experimental monotherapy and combination therapy modalities. Study Objectives for Dose Escalation Phase

• Primary Objective is to evaluate the safety and tolerability of APVO436 at the RP2D level when it is used as an adjunct to the standard of care.
• Secondary Objective is to obtain a preliminary assessment of the anti-leukemia activity of APVO436-containing experimental monotherapy and combination therapy modalities.

Conditions

AML; MDS

Keywords

APVO436

Outcome Measures

Primary Outcomes (2)

• Part 1 - Dose Escalation: Maximum Tolerated Dose

  Identify the maximum tolerated dose in dose-escalation (Phase 1) by assessment of dose-limiting toxicities

  during first 28 to 35 days of treatment

• Part 2 - Dose Expansion: Safety

  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 (14)

• Part 1 - Dose Escalation: Frequency and severity of adverse events as assessed by CTCAE v5.0

  Patient will be followed for the duration of treatment, an expected average of 6 months, and for up to 7 days following last treatment

• Part 1 - Dose Escalation: Maximum serum drug concentration

  Patient will have laboratory assessments prior to dosing on Day 1, throughout the study, and up to 7 days following last dose.

• Part 1 - Dose Escalation: Area under the concentration-time curve (AUC)

  Patient will have laboratory assessments prior to dosing on Day 1, throughout the study, and up to 7 days following last dose.

• Part 1 - Dose Escalation: Elimination of half-life

  Patient will have laboratory assessments prior to dosing on Day 1, throughout the study, and up to 7 days following last dose.

• Part 1 - Dose Escalation: Changes in T-cell populations to measure pharmacodynamics of APVO436

  Patient will have laboratory assessments prior to dosing on Day 1, throughout the study, and up to 7 days following last dose.

Study Arms (2)

PART 1 Dose Escalation - 10 dose cohorts

EXPERIMENTAL

CD123 and CD3 epsilon bispecific antibody

Biological: APVO436

PART 2 Dose expansion - 5 cohorts

EXPERIMENTAL

90 patients, 18/cohort in 5 dose expansion cohorts, will receive the recommended dose of APVO436 determined from Part 1

Biological: APVO436

Interventions

APVO436 BIOLOGICAL

APVO436

PART 1 Dose Escalation - 10 dose cohorts; PART 2 Dose expansion - 5 cohorts

Eligibility Criteria

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

You may qualify if:

• 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 ≥ 18 years
• Histologically confirmed AML or MDS:
• AML - relapsed or refractory AML and refuses or is not a candidate for intensive chemotherapy (due to prior failure or not eligible due to expected intolerance) or allogeneic transplant
• MDS - relapsed or refractory MDS with \> 5% blasts in the marrow or any blasts in the peripheral blood. Patients must have failed prior treatment with an HMA (azacitidine, decitabine, or other HMA agent); failure is defined as intolerance to HMA, lack of response (no CR by at least 6 cycles), or have IWG-defined progressive disease during or after treatment with an HMA.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Life expectancy of \> 2 months in the Investigator's opinion
• White blood cells (WBC) ≤ 25,000 cells/mm3 (may receive hydroxyurea to bring WBC count down prior to and during the first cycle of treatment with study drug if necessary)
• Creatinine ≤ 2 × 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) \< 3 × ULN
• Prothrombin time (PT) / international normalized ratio (INR) and partial thromboplastin time (PTT) \< 1.5 × ULN
• Patients and partners of childbearing potential must be willing to use adequate contraception during the study and for 2 months after last study drug administration. Adequate contraception means less than 1% chance of pregnancy may occur with proper use of the method(s).

You may not qualify if:

• A patient is not eligible to enroll into the study if they have any of the following:
• Any CNS (cerebral/meningeal) disease related to underlying malignancy
• History of seizures
• Acute promyelocytic leukemia
• Prior anti-CD123 therapy outside of this study
• Any clinically significant graft-versus-host disease (GVHD) secondary to prior allogenic transplant. Patients must be \> 90 days from transplant and have been on no immunosuppressive therapy for \> 30 days. Topical corticosteroids for minor skin rash (\<5% body surface area) is acceptable. Prior solid organ transplant is acceptable provided the patient is on no immunosuppressive therapy.
• Any therapy or experimental treatment for MDS or AML within 7 days of the first dose of study drug. Must have recovered to Grade ≤ 1 from any Grade 2 to 4 toxicity from previous treatment. 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)
• Pregnant or breast feeding
• Any other active systemic malignancies. Exceptions: noninvasive non-melanoma skin cancer, in situ carcinoma, cervical intraepithelial neoplasia, and breast or prostate cancer that is well controlled with anti-hormonal therapy
• Any current autoimmune disorder requiring immunosuppressive therapy
• Requires more than a replacement dose of corticosteroids (i.e., \> 10 mg/day of prednisone or equivalent)
• Any uncontrolled medical condition, including but not limited to:

Sponsors & Collaborators

• Aptevo Research and Development LLC: lead

Study Sites (12)

University of California, San Francisco Medical Center

San Francisco, California, 94143, United States

ACTIVE NOT RECRUITING

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

RECRUITING

University of Florida College of Medicine

Gainesville, Florida, 32610, United States

RECRUITING

Sylvester Comprehensive Cancer Center/UMHC

Miami, Florida, 33136, United States

RECRUITING

The University of Kansas Clinical Research Center

Westwood, Kansas, 66205, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

ACTIVE NOT RECRUITING

The Ohio State University Wexner Medical Center/James Cancer Hospital

Columbus, Ohio, 43210, United States

RECRUITING

Greenville Health System, Institute for Translational Oncology Research

Greenville, South Carolina, 29605, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

University of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

RECRUITING

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

ACTIVE NOT RECRUITING

Related Publications (2)

• Uckun FM, Lin TL, Mims AS, Patel P, Lee C, Shahidzadeh A, Shami PJ, Cull E, Cogle CR, Watts J. A Clinical Phase 1B Study of the CD3xCD123 Bispecific Antibody APVO436 in Patients with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome. Cancers (Basel). 2021 Aug 15;13(16):4113. doi: 10.3390/cancers13164113.

  PMID: 34439266 RESULT

• Uckun FM, Watts J, Mims AS, Patel P, Wang E, Shami PJ, Cull E, Lee C, Cogle CR, Lin TL. Risk, Characteristics and Biomarkers of Cytokine Release Syndrome in Patients with Relapsed/Refractory AML or MDS Treated with CD3xCD123 Bispecific Antibody APVO436. Cancers (Basel). 2021 Oct 21;13(21):5287. doi: 10.3390/cancers13215287.

  PMID: 34771451 RESULT

Central Study Contacts

SoYoung Kwon

CONTACT

(206) 859-6604; KwonS@apvo.com

Mona Sharma

CONTACT

SharmaM@apvo.com

Study Design

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

Model Details: The study will be conducted in 2 parts. The first part of this Phase 1B study is an open-label, multiple dose ascending dose escalation phase to determine the recommended dose (RP2D) level of APVO436 for future Phase 2 studies. The goal of the dose expansion phase of the study (Part 2) is to (i) evaluate the safety and tolerability of APVO436 at the RP2D level when it is used as an adjunct to the standard of care and (ii) obtain a preliminary assessment of the anti-leukemia activity of APVO436-containing experimental monotherapy and combination therapy modalities.

Study Record Dates

• First Submitted: August 23, 2018
• First Posted: August 27, 2018
• Study Start: December 13, 2018
• Primary Completion: December 15, 2022
• Study Completion: June 15, 2023
• Last Updated: February 10, 2022

Record last verified: 2022-02

Locations

US (12)