A multicenter, open-label, randomized, phase 2 study of venetoclax and azacitidine plus cusatuzumab versus venetoclax and azacitidine alone in newly diagnosed AML patients who are not candidates for intensive therapy

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

14 Aug 2024 → ongoing

Decision date (initial)

2024-07-19

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

OncoVerity Inc., United States

External identifiers

EU CT number

2024-510991-19-00

ClinicalTrials.gov

NCT06384261

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy, Pharmacodynamic, Pharmacokinetic

To determine the efficacy of adding cusatuzumab to venetoclax plus azacitidine (VAC) compared to venetoclax plus azacitidine (VA) alone

Secondary objectives 4

1. To determine the efficacy of adding cusatuzumab to VA compared to VA alone
2. To determine the efficacy of VAC compared to VA in the adverse, intermediate, and favorable subgroups of participants defined by a newly developed CU VA specific risk stratification model, the ELN 2022 risk model and the risk stratification model published in Bataller et al and Döhner et al.
3. To determine the safety of adding cusatuzumab to VA compared with VA alone
4. To assess the pharmacokinetics (PK) and immunogenicity of cusatuzumab

Conditions and MedDRA coding

Acute myeloid leukemia

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Men and women ≥18 years old.
2. Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.
3. Diagnosis of AML according to ICC 2022 (with the exclusion of MDS/AML with 10-19% blasts).
4. Previously untreated AML except may have received emergency leukapheresis, hydroxyurea, before study entry to control hyperleukocytosis.
5. Deemed unfit for intensive chemotherapy by meeting the criterial listed in the Protocol
6. Adequate liver and renal function, as per defined in the Protocol
7. Women of childbearing potential (WOCBP), defined as fertile women between menarche and post menopause unless permanently sterile, must have a negative highly sensitive serum β-human chorionic gonadotropin (β-hCG) or urine pregnancy test at screening
8. Must be willing to use contraception as consistent with institutional guidelines regarding the use of contraceptive methods for participants participating in clinical studies
9. Participants with HIV infection are eligible for the trial if the criteria included in the Protocol are met

Exclusion criteria 17

1. Any prior treatment for AML (except those outlined in Inclusion Criterion #4)
2. Participant has received a HMA or venetoclax for MDS or myeloproliferative neoplasm
3. Leukemic involvement in the central nervous system
4. Participants with acute promyelocytic leukemia (APL)
5. ECOG performance status of 4 for participants 18 to 74 years of age and ECOG performance status of 3 or 4 for participants ≥75 years of age
6. Use of immune suppressive agents ≤4 weeks before the first administration of cusatuzumab. Participants may be included if free of systemic corticosteroids >5 days before the first administration of cusatuzumab with the exception of corticosteroids at physiologic replacement doses
7. Received a live, attenuated vaccine within 4 weeks prior to initiation of study drug
8. Active malignancies (i.e., progressing or requiring treatment change in the last 24 months), including advanced malignant hepatic tumors, other than the disease being treated under study. Exceptions listed in the protocol.
9. Any active systemic infection
10. History of prior HSCT (allogeneic or autologous transplants).
11. Active hepatitis B or C infection or other clinically active liver diseases as defined in the Protocol
12. Congestive heart failure severity that is New York Heart Association Class III or IV
13. Unstable angina
14. Known allergies, hypersensitivity, or intolerance to cusatuzumab, venetoclax, or azacitidine or their excipients (e.g., mannitol, an excipient of azacitidine)
15. Inability or difficulty swallowing capsules/tablets, malabsorption syndrome, or any disease or medical condition significantly affecting gastrointestinal function
16. Any condition for which, in the investigator’s opinion, participation would not be in the best interest of the participant (e.g., compromise the well-being) or physical limitations that could prevent, limit, or confound the protocol-specified assessments
17. Major surgery (e.g., requiring general anesthesia) ≤4 weeks prior to initiation of study treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival (OS)

Secondary endpoints 18

1. Complete remission (CR) rate defined as rate of complete remission per European Leukemia Network (ELN) 2022
2. Event-free survival (EFS) per ELN 2022
3. Composite CR (CRc) rate = the sum of rates for CR+CRh+CRi (CRh and CRi is defined as CR with partial hematologic recovery and incomplete hematologic recovery respectively) per ELN 2022
4. Rates of CRh, CRi, and MLFS
5. Duration of complete remission defined as the time from first CR to hematological relapse or death from any cause
6. Time to first complete remission defined as time from randomization to first occurrence of CR
7. Rate of measurable residual disease (MRD) negativity in participants achieving CR, CRh or CRi per ELN 2022 guidelines for MRD testing
8. Proportion of participants proceeding to hematopoietic stem cell transplantation (HSCT)
9. OS in participants undergoing HSCT
10. Adverse events (AEs) per NCI CTCAE criteria
11. Serious AEs (SAEs) and AEs leading to study drug discontinuation
12. Incidence of dose modifications (interruptions/delays) due to AEs
13. Clinical laboratory tests, ECGs, physical examination findings, and vital signs
14. Serum concentration-time data and pharmacokinetic parameters as feasible for cusatuzumab
15. Incidence of anti-cusatuzumab antibodies
16. Incidence of neutralizing antibodies (NAb)
17. OS and CR as well as other endpoints
18. Rate of conversion from MRD negativity to MRD positivity in participants achieving CR, CRh or CRi

Investigational products

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

Test 1

Comparator 4

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

2 EU/EEA countries · 9 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 16 files

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

Application history

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