BGB-11417 for Acute Myeloid Leukemia and Myelodysplastic Syndrome

Recruiting at 85 trial locations

Overseen By BeiGene

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BeiGene

Must not be taking: B-cell lymphoma-2 inhibitors

Disqualifiers: Acute promyelocytic leukemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

260 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BGB-11417 (Sonrotoclax), both alone and with azacitidine (Vidaza or 5-azacytidine). It focuses on individuals with specific blood disorders: acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), including a type that mixes with myeloproliferative neoplasm (MPN). The study aims to determine the safety and effectiveness of these treatments. Individuals diagnosed with AML or MDS who can manage daily life with these conditions might be suitable candidates for this trial. As a Phase 1/Phase 2 trial, this research seeks to understand how the treatment works in people and measures its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking medical advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of BGB-11417 and azacitidine is generally well tolerated by patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In earlier studies, this treatment demonstrated activity against leukemia cells, helping to combat them. Patients reported managing the treatment well without severe side effects.

One study found that most patients noticed positive effects by the end of the first treatment cycle. This suggests the treatment could be safe and effective early on. However, as this trial is in its early stages, more research is needed to fully understand any potential risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BGB-11417 for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) because it represents a novel approach by targeting a different mechanism than traditional treatments like chemotherapy. BGB-11417 works as a BCL-2 inhibitor, aiming to induce cancer cell death more effectively by disrupting the survival signals of the cancer cells, which is different from the DNA damage approach of azacitidine. This targeted action could potentially lead to better outcomes with fewer side effects. Additionally, the trial explores the interaction of BGB-11417 with posaconazole, which could provide insights into optimizing treatment combinations for enhanced efficacy.

What evidence suggests that this trial's treatments could be effective for AML and MDS?

In this trial, participants with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) will receive BGB-11417, also known as sonrotoclax, with some receiving it alongside azacitidine. Previous studies have shown that BGB-11417 holds promise for treating AML and MDS. Research indicates that combining BGB-11417 with azacitidine helps fight leukemia cells. Early results revealed that many patients experienced complete remission (CR), meaning the signs of cancer were reduced or disappeared, by the end of the first treatment cycle. The treatment has generally been well tolerated, suggesting it is relatively safe for patients. Overall, the combination of BGB-11417 and azacitidine has shown encouraging results in combating these blood cancers. ^{1 2 6 7 8}

Who Is on the Research Team?

David Simpson, MD

Principal Investigator

BeiGene

Are You a Good Fit for This Trial?

This trial is for adults with certain blood disorders like AML, MDS, or MDS/MPN. They should be relatively active (able to care for themselves), have kidneys and liver working well, and expected to live more than 12 weeks. People can't join if they've had leukemia in the brain, certain other cancers in the last 2 years, specific blood diseases including myelofibrosis or polycythemia vera, or previous treatments with similar drugs.

Inclusion Criteria

I have been diagnosed with AML, MDS, or MDS/MPN and can care for myself.

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; Life expectancy of > 12 weeks; Ability to comply with the requirements of the study.

Exclusion Criteria

My leukemia has spread to my brain or spinal cord.

I haven't had cancer in the last 2 years, except for certain treated early-stage cancers.

I have not taken B-cell lymphoma-2 inhibitors or azacitidine, or I meet the criteria for HMA failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BGB-11417 as monotherapy or in combination with azacitidine on a 28-day cycle

24 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• BGB-11417

Trial Overview The study tests BGB-11417 alone and combined with azacitidine to find a safe dose and see how effective it is against acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Posaconazole is also used as part of the treatment regimen.

How Is the Trial Designed?

Group I: Parts 1 and 2: MDS Cohorts Experimental Treatment 2 Interventions

Participants with MDS will receive BGB-11417 and azacitidine on a 28-day cycle.

Group II: Parts 1 and 2: AML Cohorts Experimental Treatment 2 Interventions

Participants with AML will receive BGB-11417 and azacitidine on a 28-day cycle.

Group III: Part 3: AML and MDS Cohorts Experimental Treatment 3 Interventions

Participants with AML and MDS will receive BGB-11417 and azacitidine on a 28-day cycle. A subset of the participants will receive a modified second cycle of treatment to explore drug-drug interactions (DDI) with posaconazole.

Group IV: Part 3: AML and MDS Cohort Experimental Treatment 1 Intervention

Participants with MDS and R/R AML (China only) will receive BGB-11417 on a 28-day cycle.

Azacitidine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Published Research Related to This Trial

The Vidaza Access Program in Belgium successfully facilitated access to azacitidine treatment for 175 patients with myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML) by streamlining the approval process for patient dossiers.

Out of the 175 patient dossiers submitted, 163 were approved by Celgene, demonstrating the program's effectiveness in ensuring timely treatment initiation without financial risk to hospitals, which is crucial for patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine access program for Belgian patients with myelodysplastic syndromes, acute myeloid leukemia or chronic myelomonocytic leukemia. Meers, S., Selleslag, D., Potier, H., et al.[2018]

Azacitidine is an effective and well-tolerated treatment for patients with higher-risk myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML), including older patients who are ineligible for stem cell transplants, as demonstrated in pivotal phase 3 trials.

It is the only approved hypomethylating agent that has been shown to prolong overall survival compared to conventional care, making it the recommended first-line treatment for most patients with higher-risk MDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine: A Review in Myelodysplastic Syndromes and Acute Myeloid Leukaemia. Scott, LJ.[2022]

In a study of 149 patients with higher-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML), azacitidine treatment resulted in a median progression-free survival (PFS) of 10.9 months and an overall survival (OS) of 14.1 months, demonstrating its effectiveness in a real-world clinical setting.

The safety profile of azacitidine was consistent with previous clinical trials, and factors such as Eastern Cooperative Oncology Group (ECOG) performance status and red blood cell transfusion prior to treatment were identified as predictive factors for better PFS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of performance status and transfusion dependency on outcome of patients with myelodysplastic syndrome, acute myeloid leukemia and chronic myelomonocytic leukemia treated with azacitidine (PIAZA study). Wehmeyer, J., Zaiss, M., Losem, C., et al.[2019]

In a Japanese subgroup of the phase 3 VIALE-A trial, venetoclax-azacitidine significantly improved overall survival rates compared to placebo-azacitidine, with 67% of patients alive at 12 months versus 46% in the placebo group.

The treatment also resulted in a high complete response (CR) and CR with incomplete hematologic recovery (CRi) rate of 67%, while maintaining a safety profile similar to the global study, indicating it is a viable first-line treatment for Japanese patients with acute myeloid leukemia ineligible for intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. Yamamoto, K., Shinagawa, A., DiNardo, CD., et al.[2023]

In the HiDDAV study involving 42 newly diagnosed AML patients, higher doses of venetoclax (600 mg daily) were found to be tolerable but did not show significant clinical improvement compared to the standard 400 mg dose.

The study revealed that using minimal residual disease (MRD) status to guide the discontinuation of azacitidine did not lead to better outcomes in terms of duration of response or overall survival, suggesting that alternative strategies are needed to optimize treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher-dose venetoclax with measurable residual disease-guided azacitidine discontinuation in newly diagnosed acute myeloid leukemia. Gutman, JA., Winters, A., Kent, A., et al.[2023]

The combination of azacitidine and venetoclax is safe and well-tolerated in patients with high-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia, with a recommended phase 2 dose established as azacitidine 75 mg/m2 for 5 days plus venetoclax 400 mg for 14 days.

The treatment showed a high overall response rate of 87% among the 23 enrolled patients, indicating promising preliminary activity for this combination therapy in treatment-naive and relapsed or refractory cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine plus venetoclax in patients with high-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia: phase 1 results of a single-centre, dose-escalation, dose-expansion, phase 1-2 study. Bazinet, A., Darbaniyan, F., Jabbour, E., et al.[2022]

In patients with newly diagnosed unfit acute myeloid leukemia (AML), the combination of azacitidine and venetoclax is a standard first-line treatment.

However, patients with TP53-mutated AML and poor-risk cytogenetics do not benefit from adding venetoclax to azacitidine, suggesting that alternative treatment regimens should be considered for these individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TP53 or Not TP53: That Is the Question. Green, SD., Zeidner, JF.[2023]

In a long-term follow-up study of patients with acute myeloid leukemia (AML), the combination of venetoclax with azacitidine or decitabine showed a high complete remission rate of 71% and 74%, respectively, indicating strong efficacy for patients ineligible for intensive chemotherapy.

The median overall survival for patients treated with venetoclax plus azacitidine was 16.4 months, and 16.2 months for those treated with decitabine, demonstrating that this treatment combination is a viable frontline option for AML patients who cannot undergo more aggressive therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax with azacitidine or decitabine in patients with newly diagnosed acute myeloid leukemia: Long term follow-up from a phase 1b study. Pollyea, DA., Pratz, K., Letai, A., et al.[2021]

In a phase II study involving 60 older or unfit patients with newly diagnosed acute myeloid leukemia (AML), the combination of venetoclax with cladribine and low-dose cytarabine alternating with venetoclax and 5-azacitidine resulted in a high composite complete response rate of 93%.

The treatment showed promising overall survival and disease-free survival rates, with only one death occurring within 4 weeks, indicating that this regimen is effective and has a favorable safety profile for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia. Kadia, TM., Reville, PK., Wang, X., et al.[2023]

In a study of 259 adults with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), the combination of azacitidine (AZA) and vorinostat (VOR) did not improve overall response rates or survival compared to AZA alone, indicating that VOR does not enhance the efficacy of AZA in treating these conditions.

The study identified specific genetic mutations (CDKN2A, IDH1, and TP53) that are associated with poorer overall survival, suggesting that these mutations could help predict patient outcomes and that AZA may work by inducing cell-cycle arrest in affected cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of Azacitidine Therapy in Acute Myeloid Leukemia Is not Improved by Concurrent Vorinostat Therapy but Is Predicted by a Diagnostic Molecular Signature. Craddock, CF., Houlton, AE., Quek, LS., et al.[2022]

Azacitidine (Vidaza) is the only drug approved in the EU that significantly prolongs survival in adults with high-risk myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML), making it a crucial treatment option for patients not eligible for stem cell transplantation.

The treatment is associated with a lower risk of AML progression and higher rates of remission and blood transfusion independence, while maintaining an acceptable safety profile, with peripheral cytopenias being the most common side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine: a review of its use in higher-risk myelodysplastic syndromes/acute myeloid leukaemia. Keating, GM.[2021]

Citations

1. beonemedinfo.com beonemedinfo.com/CongressDocuments/Montesinos_BGB-11417-103_RR_AML_EHA_Poster_2025.pdf

Updated Safety and Antileukemic Activity Data for ... Sonrotoclax + azacitidine combination treatment was generally well tolerated and demonstrated antileukemic activity in patients with R/R AML.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11938950/

Risk-stratified treatment of sonrotoclax with chemotherapy in ... This study protocol evaluates the efficacy and safety of sonrotoclax combined with chemotherapy as a first-line treatment for newly diagnosed ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04771130

NCT04771130 | A Study of BGB-11417 in Participants With ... The study will determine the safety, tolerability, recommended Phase 2 dose (RP2D) and preliminary efficacy of BGB-11417 as monotherapy and in combination ...

4. journals.lww.com journals.lww.com/hemasphere/fulltext/2022/06003/p590__preliminary_safety_and_efficacy_of.489.aspx

p590: preliminary safety and efficacy of bgb-11417, ... Preliminary results show that a 10-day regimen of BGB-11417 plus azacitidine resulted in a majority of CR observed by the end of Cycle 1 and was well tolerated ...

5. beonemedaffairs.com beonemedaffairs.com/us/wp-content/uploads/sites/11/2025/06/BGB-11417-103-TN-AML_Shortt_Poster_EHA_Final.pdf

Updated Safety & Antileukemic Activity Data of Sonrotoclax ... Sonrotoclax + azacitidine combination treatment was generally well tolerated and demonstrated antileukemic activity in patients with TN ...

6. library.ehaweb.org library.ehaweb.org/eha/2025/eha2025-congress/4159884/jake.shortt.updated.safety.26.antileukemic.activity.data.of.sonrotoclax.html

UPDATED SAFETY & ANTILEUKEMIC ACTIVITY DATA OF ... UPDATED SAFETY & ANTILEUKEMIC ACTIVITY DATA OF SONROTOCLAX (BGB-11417), A POTENT AND SELECTIVE BCL2 INHIBITOR, IN TREATMENT-NAIVE PATIENTS ...

7. beonemedinfo.com beonemedinfo.com/CongressDocuments/Montesinos_BGB-11417-103_RR_AML_EHA_Abstract_2025.pdf

updated safety and antileukemic activity data for sonrotoclax Methods: BGB-11417-103 (NCT04771130) is an ongoing, global, dose-escalation/expansion study of sonrotoclax + azacitidine in patients with AML, myelodysplastic ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04771130

NCT04771130 | A Study of BGB-11417 in Participants With ... The study will determine the safety, tolerability, recommended Phase 2 dose (RP2D) and preliminary efficacy of BGB-11417 as monotherapy and in combination ...