A Clinical Study of Cusatuzumab Plus Azacitidine in Patients With Newly Diagnosed Acute Myeloid Leukemia who are not Candidates for Intensive Chemotherapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

OncoVerity Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 Aug 2019 → 6 Mar 2026

Decision date (initial)

2024-07-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

OncoVerity, Inc

External identifiers

EU CT number

2024-513283-26-00

EudraCT number

2019-000473-23

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Others, Pharmacokinetic, Therapy, Safety, Efficacy

To determine the efficacy of cusatuzumab in combination with azacitidine in patients with previously untreated acute myeloid leukemia (AML) who are not eligible for intensive chemotherapy

Secondary objectives 6

1. To determine the below responses a) Complete response (CR) b) CR with incomplete recovery (CRi) c) CR with partial hematological revovery (CRh) d) CR without MRD (CRMRD-) e) Morphologic leukemia-free state (MLFS) f) Partial response (PR) g) Stable disease h) Relapse after CR, CRi, CRh i) Progressive Disease
2. To assess time to response and duration of response
3. To determine transfusion independence
4. To assess the safety profile of cusatuzumab in combination with azacitidine
5. To assess the pharmacokinetics of cusatuzumab alone and in combination with azacitidine
6. To assess the immunogenicity of cusatuzumab alone and in combination with azacitidine

Conditions and MedDRA coding

Acute Myeloid Leukemia

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. ≥18 years of age
2. Criterion modified per Amendment 1 2.1. AML according to WHO 2016 criteria and fulfilling all of the following criteria that defines those who are "not candidates for intensive chemotherapy": ● ≥75 years of age or ● <75 years of age with of at least one of the following comorbidities: o Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 o Severe cardiac comorbidity defined as congestive heart failure or ejection fraction ≤50% o Severe pulmonary comorbidity defined as documented pulmonary disease with lung diffusing capacity for carbon monoxide (DLCO) ≤65% of expected, or forced expiratory volume in 1 second (FEV1) ≤65% of expected or dyspnea at rest requiring oxygen o Moderate hepatic impairment defined according to National Cancer Institute (NCI) organ dysfunction classification criteria (total bilirubin ≥1.5 up to 3 times upper limit of normal [ULN]) o Creatinine clearance <45 mL/ min/1.73 m² (by MDRD formula) o Comorbidity that, in the Investigator's opinion, makes the patient unsuitable for intensive chemotherapy and must be documented and approved by the Sponsor before randomization
3. Criterion numbering modified per Amendment 1 3.1. De novo or secondary AML;
4. Criterion modified per Amendment 1 4.1. Previously untreated AML (except: emergency leukapheresis, hydroxyurea, and /or 1 dose of cytarabine [eg, 1-2g/m^2] during the screening phase to control hyperleukocytosis. Theses treatments mst be discontinued ≥ 24 hours prior to start of study drug). Empiric all trans retinoic acid (ATRA) treatment for presumed acute promyelocytic leukemia (APL) is permited but APL mus be ruled out and ATRA mus be discontinued ≥ 24 hours prior to the start of the study drug;
5. Criterion numbering modified per Amendment 1 5.1. Not eligible for an allogeneic hematopoietic stem cell transplantation.
6. Criterion numbering modified per Amendment 1 6.1. ECOG Performance Status score of 0, 1 or 2.
7. Criterion numbering modified per Amendment 1 7.1. The following clinical laboratory values at screening: ● Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <3 times ULN; for participants with leukemic infiltration of the liver (documented by biopsy or imaging), AST and ALT <5 times ULN is permitted ● Total bilirubin ≤ 3 times ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin or in case of liver infiltration by AML (documented by biopsy or imaging) serum total bilirubin <5 times ULN ● Creatinine Clearance >30 mL/min (by MDRD formula)
8. Criterion numbering modified per Amendment 1 8.1. A woman must be either: ● Not of childbearing potential: postmenopausal (>45 years of age with amenorrhea for at least 12 months); ● Of childbearing potential and practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for participants participating in the clinical study while receiving study tratment and for at least 3 months after the last dose of study treatment. A woman of childbearing potential must have a negative highly-sensitive serum (β-human chorionic gonadotropin [β-hCG]) or urine pregnancy test at screening. A woman fo childbearing potential must agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study treatment and for 3 months after the last dose of study treatment. Note: If the childbearing potential changes after start of the study (eg, woman who is not heterosexually active becomes active, premenarchal woman experiences menarche) a woman must begin a highly effective method of birth control, as described above.
9. Criterion modified per Amendment 1 9.1. A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control eg, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository for at least 3 months after last study treatment. ● Must agree to not donate sperm during the study treatment and for 3 months after the last dose of study treatment. ● Not plan to father a chld during the study treatment and for 3 months after the last dose os study treatment.
10. Criterion modified per Amendment 10.1. Must sign and informed consent form (ICF) indicating that he or she (or their legally acceptable representative) understands the purpose of, and procedures required for, the study and is willing to participate in the study.

Exclusion criteria 14

1. Criterion modified per Amendment 1 1.1. Acute promyelocytic leukemia
2. Leukemic involvement or clinical symptoms of leukemic involvement of the central nervous system.
3. Criterion modified per Amendment 1 3.1. Use of immune suppressive agents for the past 4 weeks before the first administration of cusatuzumab on Cycle 1 Day 3. For regular use of systemic corticosteroids, participants may only be included if free of systemic corticosteroids for a minimum of 5 days before the first administration of cusatuzumab. Treatment of adrenal insufficiency with physiologic replacement doses of corticosteroids are allowed.
4. Prior treatment with a hypomethylating agent for treatment of AML or MDS
5. Criterion modified per Amendment 1 5.1. Active malignancies (ie, progressing or requiring treatment in the last 24 months) other than the disease being treated under study. The only allowed exceptions are: ● Non-melanoma skin cancer treated within the last 24 months that is considered completely cured ● Adequately treated breast lobular carcinoma in situ and breast ductal carcinoma in situ ● Adequately treated cervical carcinoma in situ without evidence of disease ● History of localized breast cancer and receiving antihormonal agents, or history of localized prostate cancer (N0M0) and receiving androgen deprivation therapy ● Malignancy that is considered cured with minimal risk of recurrence
6. Criterion modified per Amendment 1 6.1. Any active systemic infection
7. Criterion modified per Amendment 1 7.1. A history of human immunodeficiency virus (HIV) antibody positive or tests positive for HIV at screening
8. Criterion modified per Amendment 1 8.1. Active hepatitis B or C infection or other clinically active liver disease Seropositive for hepatitis B: defined by a positive test for hepatitis B surface antigen [HBsAg]. Participants with resolved infection (ie, participants who are HBsAg negative with antibodies to total hepatitis B core antigen [anti-HBc] with or without the presence of hepatitis B surface antibody [anti-HBs]) must be screened using real-time polymerase chain reaction (RT-PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are RT-PCR positive will be excluded. Participants with serologic findings suggestive of HBV vaccination (antiHBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by RT-PCR. Known Hepatitis C infection or positive serologic testing for Hepatitis C (anti-HCV antibody)
9. New York Heart Association Class IV heart failure or ongoing unstable angina
10. Known allergies, hypersensitivity, or intolerance to cusatuzumab or azacitidine or its excipients (ie, mannitol, an excipient of azacitidine).
11. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or physical limitations that could prevent, limit, or confound the protocol-specified assessments.
12. Criterion modified per Amendment 1 12.1. Major surgery, (eg, requiring general anesthesia) within 4 weeks prior to initiation of the study.
13. Women who are breastfeeding.
14. Received a live, attenuated vaccine within 4 weeks prior to initiation of study treatment. NOTE: Investigators should ensure that all study enrollment (inclusion/exclusion) criteria have been met at screening and prior to the first dose of study intervention. If a participant's clinical status changes (including any available laboratory results or receipt of additional medical records) after screening but before the first dose of study intervention is given such that he or she no longer meets all eligibility criteria, then the participant should be excluded from participation in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Complete response (CR) rate per ELN 2017 (Dohner 2017)

Secondary endpoints 11

1. Rate of CRh
2. Rate of CR + CRh
3. Rate of Cri
4. Overall response rate (ORR) = Rate of CR+ CRh+ CRi
5. Rate of CR without MRD
6. Rate of MRD negativity among participants achieving CR, CRh, CRi, or MLFS; defined as less than 1 blast or leukemic stem cell in 1,000 leukocytes (MRD level <10^-3)
7. Time to response, defined as time from randomization in Part 1 or enrollment in Part 2 to achieving the first response of CR, CRh, or CRi; duration of response, defined as time from achieving the first response of CR, CRh, or CRi to disease relapse or death from any cause.
8. Transfusion independence (RBC or platelets) is defined as a period of at least 56 consecutive days with no transfusion between first dose of study drug and the last dose of study drug + 30 days.
9. Safety profile of Adverse Events (AE) and Serious Adverse Events (SAE)
10. Pharmacokinetics
11. Immunogenicity / anti-drug antibody testing

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

OncoVerity Inc.

Sponsor organisation

OncoVerity Inc.

Address

12635 East Montview Boulevard

City

Aurora

Postcode

80045-7335

Country

United States

Scientific contact point

Organisation

OncoVerity Inc.

Contact name

OncoVerity Help Desk

Public contact point

Organisation

OncoVerity Inc.

Contact name

OncoVerity Help Desk

Third parties 7

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications