A Phase 1b/2, Open-Label, Dose Finding, and Expansion Study of the Bcl-2 Inhibitor BGB-11417 in Patients With Myeloid Malignancies BGB-11417

What's the purpose of this trial?

The study will determine the safety, tolerability, recommended Phase 2 dose (RP2D) and preliminary efficacy of BGB-11417 as monotherapy and in combination with azacitidine in participants with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)or MDS/myeloproliferative neoplasm (MPN) .

This trial is currently open and accepting patients.


What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Key Inclusion Criteria:

1. Confirmed diagnosis of one of the following by 2016 World Health Organization criteria:

* AML, nonacute promyelocytic leukemia
* MDS
* MDS/MPN
2. Eastern Cooperative Oncology Group performance status of 0 to 2.
3. Adequate organ function defined as:

* Creatinine clearance ≥ 50 milliliters/minute (mL/min) (or between 30 and 49 mL/min in unfit AML cohort)
* Adequate liver function
4. Life expectancy of \> 12 weeks.
5. Ability to comply with the requirements of the study.

Key Exclusion Criteria:

1. A diagnosis of acute promyelocytic leukemia.
2. Prior malignancy within the past 2 years, except for curatively treated localized skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate cancer.
3. Antecedent MPN including myelofibrosis, essential thrombocytosis, polycythemia vera, or chronic myelogenous leukemia with or without BCR-ABL1 translocation and AML with BCR-ABL1 translocation.
4. Prior therapy with a B-cell lymphoma-2 inhibitor or azacitidine except for participants who meet HMA-failure criteria
5. Known central nervous system involvement by leukemia.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Additional Trial Information

Phase 1/2

Enrollment: 260 patients (estimated)

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Published Results

Preliminary Safety and Efficacy of Bgb-11417, a Novel Bcl-2 Inhibitor, in Combination with Azacitidine in Patients with Acute Myeloid Leukemia (AML)

November 15, 2022

As of June 1, 2022, 51 pts with AML were treated (16 in cohort 1; 17 in cohort 2; 14 in cohort 3; 4 in cohort 4). Median age was 77 yrs (TN, n=28) and 64 yrs (R/R, n=23) (Table 1). At baseline, 23 pts (45.1%) had adverse-risk cytogenetics, 37 (72.5%) had grade ≥3 neutropenia, and 27 (52.9%) had grade ≥3 thrombocytopenia.


At a median follow-up of 2.8 mo (range 0.1-12.3) and median duration of treatment of 1.9 mo (range 0.0-12.3), 2 of 41 evaluable pts experienced DLTs (grade 4 neutropenia and grade 4 thrombocytopenia at 80 mg) (Table 2), which did not meet the safety stopping protocol criteria. Laboratory tumor lysis syndrome (TLS; Howard criteria) was observed in 1 pt (160 mg x 10 days) with a known history of chronic kidney disease; TLS resolved within 4 days.


Twenty-one (41%) pts discontinued study drugs: 7 (13.7%) due to AEs, 5 (9.8%) due to disease progression, 4 (7.8%) proceeded to transplant, 3 (5.9%) withdrew consent, 1 (2.0%) per investigator decision, and 1 (2.0%) started new anti-cancer treatment.


The most common TEAEs were neutropenia (58.8%), thrombocytopenia (45.1%), anemia (43.1%), febrile neutropenia (33.3%), nausea (39.2%), and constipation (37.3%). Neutropenia was the most common grade ≥3 TEAE observed in 30 (58.8%) pts; most cases did not require dose modification. Grade ≥3 infections occurred in 23 (45.1%) pts, mostly in cycle 1. The general incidence of febrile neutropenia and infections decreased with subsequent cycles. Four (7.8%) pts died due to unrelated TEAEs: bronchopulmonary aspergillosis, pneumonia, pulmonary sepsis, and possible intracranial hemorrhage after a fall. TEAEs leading to dose reduction (5.9%) or dose interruption (11.8%) were infrequent.


In TN AML, complete remission (CR)/CR with partial hematologic recovery (CRh) was achieved in 16 (59.3%) and CR in 13 (48.1%) evaluable pts (Table 1). Of the 13 pts in CR, 7 (53.8 %) reached CR by end of cycle 1. In cohort 2 with the longest follow-up, CR was achieved in 8 (72.7%) pts with TN AML. Notably, 7 of these pts are continuing study treatment (median of 5 cycles, range 1-12) without progression. In R/R AML, CR/CRh was seen in 50% of evaluable pts, with a CR rate of 25%. Nine (50.0%; 6 TN, 3 R/R) of 18 evaluable pts with CR/CRh achieved MRD negativity (<0.1% per ELN 2018).


In pts with AML treated with 40, 80, and 160 mg, PK increased in a dose-dependent manner at steady state with no drug-drug interaction observed with aza.

Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.

California

City of Hope Comprehensive Cancer Center Beckman Research Institute

Duarte, CA

Open and Accepting

Florida

Tampa General Hospital Cancer Institute

Tampa, FL

Open and Accepting

Maryland

Maryland Oncology Hematology (Columbia)

Columbia, MD

Open and Accepting

Pennsylvania

UPMC Hillman Cancer Center University of Pittsburgh Medical Center (UPMC)

Pittsburgh, PA

Not Yet Accepting

Texas

MD Anderson Cancer Center The University of Texas

Houston, TX

Open and Accepting

Wisconsin

Medical College of Wisconsin Froedtert Hospital

Milwaukee, WI

Open and Accepting
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