Clinical trial NCT06068868: Study to Evaluate Adverse Events and Movement of Intravenously (IV) Infused ABBV-787 in Adult Participants With Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)
Official title: A Phase 1 First-in-Human Study Evaluating Safety, Pharmacokinetics and Efficacy of ABBV-787 in Adult Subjects With Acute Myeloid Leukemia (AML)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Keywords: Acute Myeloid Leukemia
AML
ABBV-787
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2023-10-05
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Acute myeloid leukemia (AML) is the second most common type of leukemia diagnosed in adults and children, but most cases occur in adults. This study is to evaluate how safe ABBV-787 is and how it moves within the body in adult participants with relapsed/refractory (R/R) acute myeloid leukemia (AML). Adverse events and maximum tolerated dose (MTD) of ABBV-787 will be assessed.

ABBV-787 is an investigational drug being developed for the treatment of AML. Participants will receive ABBV-787 in escalating doses until the maximum tolerated dose (MTD) is determined. Approximately 60 adult participants with a diagnosis of AML will be enrolled worldwide.

Participants will receive intravenous (IV) infusions of ABBV-787 during the approximately 3 year duration a participant is followed.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests and checking for side effects.


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Laboratory Criteria matching those outlined in the protocol.
* QT interval corrected for heart rate (QTc) \<= 470 msec using Fridericia's correction, and no other clinically significant cardiac abnormalities.
* Documented diagnosis of non-promyelocytic acute myeloid leukemia (AML), per 2022 European Leukemia Net (ELN) criteria.
* Participants with relapsed/refractory (R/R) acute myeloid leukemia (AML) who have been treated with up to 3 prior lines of therapy and are refractory to or intolerant of all established AML therapies that are known to clearly provide clinical benefit at the judgement of the investigator.
* Must have a white blood cell (WBC) count \< 25 × 10\^9 /L prior to initiation of study drug (Note: Hydroxyurea or leukapheresis is permitted to meet this criterion and for use through Cycle 3 to control for hyperleukocytosis.).

Exclusion Criteria:

* Have received a CD33-targeting therapy within 3 months prior to the first dose of ABBV-787.
* Stem cell transplant within 3 months prior to first dose of study drug.
* Have received anticancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within 14 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of ABBV-787.
* History of documented pneumonitis that required treatment with systemic steroids within the last 6 months, nor any evidence of active pneumonitis.
* Unresolved toxicity of Grade \>= 2 from prior anticancer therapy, or to levels dictated in the eligibility criteria, with the exception of alopecia.
* Known active severe or poorly controlled acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Primary outcomes:
measure: Number of Participants with Adverse Events (AE)
timeFrame: Up to Approximately 3 Years
measure: Maximum Tolerated Dose (MTD) Based on Dose-Limiting Toxicities (DLT)
timeFrame: Up to approximately 28 Days
Secondary outcomes:
measure: Area Under the Plasma Concentration-time Curve (AUC) of ABBV-787
timeFrame: Up to Approximately 1 Year
measure: Maximum Observed Concentration (Cmax) of ABBV-787
timeFrame: Up to Approximately 1 Year
measure: Time to Cmax (Tmax) of ABBV-787
timeFrame: Up to Approximately 1 Year
measure: Half-life (t1/2) of ABBV-787
timeFrame: Up to Approximately 1 Year
measure: Total Antibody Concentration
timeFrame: Up to Approximately 1 Year
measure: Plasma Concentrations of Unconjugated Bromodomain and Extra-terminal Domain (BET) Degrader Payload
timeFrame: Up to Approximately 1 Year
measure: Antidrug Antibody (ADA)
timeFrame: Up to Approximately 1 Year
measure: Neutralizing Antibody (nAb)
timeFrame: Up to Approximately 1 Year
measure: Percentage of Participants Achieving Complete Remission (CR)
timeFrame: Up to Approximately 1 Year
measure: Rate of Participants Achieving CR with partial hematologic recovery (CRh)
timeFrame: Up to Approximately 1 Year
measure: Rate of Participants Achieving CR with incomplete hematologic recovery (CRi)
timeFrame: Up to Approximately 1 Year
measure: Rate of Participants Achieving Composite CR (CR, CRh, or CRi)
timeFrame: Up to Approximately 1 Year
measure: Rate of Participants Achieving Partial Remission (PR)
timeFrame: Up to Approximately 1 Year
measure: Duration of Response (DOR)
timeFrame: Up to Approximately 1 Year
measure: Number of Participants proceeding to hematopoietic stem cell transplant (HSCT)
timeFrame: Up to Approximately 3 Years
measure: Event-free Survival (EFS)
timeFrame: Up to Approximately 3 Years
measure: Relapse free survival (RFS)
timeFrame: Up to Approximately 3 Years
measure: Overall survival (OS)
timeFrame: Up to Approximately 3 Years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope /ID# 253727
state: California
city: Sacramento
country: United States
facility: University of California Davis Health /ID# 252723
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine /ID# 252724
state: Connecticut
city: Chicago
country: United States
facility: Northwestern Memorial Hospital /ID# 252800
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical /ID# 252764
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland, Baltimore /ID# 253726
state: Maryland
city: Grand Rapids
country: United States
facility: Cancer & Hematology Centers /ID# 252803
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center-Koch Center /ID# 252515
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College /ID# 252516
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania /ID# 252789
state: Pennsylvania
city: Austin
country: United States
facility: St. David's South Austin Medical Center /ID# 252790
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center /ID# 252514
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center /ID# 253730
state: Washington
city: Milwaukee
country: United States
facility: Wisconsin Medical Center /ID# 252513
state: Wisconsin
city: Clayton
country: Australia
facility: Monash Health - Monash Medical Centre /ID# 253841
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Ctr /ID# 252517
state: Victoria
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center /ID# 252913
state: Tel-Aviv
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center /ID# 252914
state: Tel-Aviv
city: Jerusalem
country: Israel
facility: Hadassah Medical Center-Hebrew University /ID# 252915
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East /ID# 252519
state: Chiba
city: Yamagata-shi
country: Japan
facility: Yamagata University Hospital /ID# 254105
state: Yamagata
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital /ID# 252916
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center /ID# 253955
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System Severance Hospital /ID# 253956
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: