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N-[4-({[(1R,4R)-4-Hydroxy-4-Methylcyclohexyl]Methyl}Amino)-3- Nitrobenzene-1-Sulfonyl]-4-(2-{(2S)-2-[2-(Propan-2-Yl)Phenyl]Pyrrolidin1-Yl}-7-Azaspiro[3.5]Nonan-7-Yl)-2-[(1H-Pyrrolo[2,3-B]Pyridin-5- Yl)Oxy]Benzamide

This article summarizes clinical trials investigating the use of BGB-11417, also known as sonrotoclax, for treating various blood cancers. BGB-11417 is a novel Bcl-2 inhibitor being studied alone and in combination with other drugs for conditions like chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), multiple myeloma (MM), and myeloid malignancies. The trials aim to determine the safety, efficacy, and optimal dosing of BGB-11417 in these patient populations.

Table of Contents

Overview of BGB-11417

BGB-11417, also known as sonrotoclax, is an investigational drug being developed by BeiGene for the treatment of various blood cancers[1]. It is a new type of medication called a BCL-2 inhibitor. BCL-2 is a protein that helps cancer cells survive, so blocking it can potentially kill cancer cells.

The drug comes in the form of film-coated tablets that are taken by mouth[2]. It is currently being studied in clinical trials to determine if it is safe and effective for treating certain types of blood cancers, either alone or in combination with other medications.

How BGB-11417 Works

BGB-11417 works by targeting and inhibiting a protein called BCL-2. This protein helps keep cancer cells alive by preventing them from undergoing a natural process of cell death called apoptosis. By blocking BCL-2, BGB-11417 aims to make cancer cells more susceptible to dying off[3].

This mechanism of action is similar to another approved drug called venetoclax, but BGB-11417 is a newer compound that may have some advantages. Researchers are studying whether it could be more potent or have fewer side effects than existing treatments.

Conditions Being Studied

BGB-11417 is currently being investigated for several types of blood cancers, including:

  • Chronic lymphocytic leukemia (CLL): A slow-growing cancer of white blood cells[2]
  • Mantle cell lymphoma (MCL): A rare type of non-Hodgkin lymphoma[1]
  • Multiple myeloma: A cancer of plasma cells in the bone marrow[4]
  • Acute myeloid leukemia (AML): A fast-growing cancer of myeloid cells[5]
  • Myelodysplastic syndromes (MDS): A group of disorders where blood cells don’t develop properly[5]

These conditions are all types of blood cancers that affect different types of blood cells. BGB-11417 is being studied in patients whose cancer has either relapsed (come back after treatment) or is refractory (not responding well to other treatments).

Current Clinical Trials

Several clinical trials are currently underway to evaluate BGB-11417:

  • A phase 1/2 study in patients with relapsed or refractory mantle cell lymphoma[1]
  • A phase 3 study comparing BGB-11417 plus zanubrutinib to venetoclax plus obinutuzumab in previously untreated chronic lymphocytic leukemia[2]
  • A phase 1b/2 study in combination with other drugs for relapsed or refractory multiple myeloma[4]
  • A phase 1b/2 study in combination with azacitidine for myeloid malignancies (AML, MDS, and MDS/MPN)[5]

These trials are testing BGB-11417 both alone and in combination with other cancer drugs. They aim to determine the best doses, evaluate how well it works, and monitor for any side effects.

Safety and Side Effects

As BGB-11417 is still in clinical trials, its full safety profile is not yet known. However, researchers are closely monitoring for side effects. Some potential side effects being watched for include:

  • Low blood cell counts (neutropenia, thrombocytopenia, anemia)
  • Infections
  • Tumor lysis syndrome (a condition caused by rapid breakdown of cancer cells)
  • Gastrointestinal effects (nausea, diarrhea)
  • Fatigue

It’s important to note that not all patients will experience these side effects, and the trials are designed to find the safest and most effective doses[1].

Future Directions

BGB-11417 is still in the early to middle stages of clinical development. If the current trials show promising results, it may advance to larger studies and potentially become a new treatment option for certain blood cancers.

Researchers are particularly interested in how BGB-11417 compares to existing treatments and whether it could be effective for patients who haven’t responded well to other therapies. The ongoing studies will help determine which patients might benefit most from this new drug.

As with any experimental treatment, it’s important for patients to discuss the potential risks and benefits with their healthcare providers and to consider clinical trial participation carefully.

Trial Name Cancer Type Phase Treatment Primary Objectives
2022-500687-35-00 Relapsed/Refractory Mantle Cell Lymphoma 1/2 BGB-11417 monotherapy Safety, tolerability, MTD, RP2D, efficacy
2023-504653-12-00 Richter Transformation (CLL to DLBCL) 2 BGB-11417 + zanubrutinib + tislelizumab +/- sonrotoclax Safety, tolerability, efficacy
2023-506948-17-00 Previously Untreated CLL 3 BGB-11417 + zanubrutinib vs. venetoclax + obinutuzumab Progression-free survival
2023-507751-30-00 Relapsed/Refractory Multiple Myeloma 1b/2 BGB-11417 +/- dexamethasone, carfilzomib, daratumumab, or pomalidomide Safety, tolerability, MTD, RP2D, efficacy
2023-508881-14-00 Myeloid Malignancies (AML, MDS, MDS/MPN) 1b/2 BGB-11417 +/- azacitidine Safety, tolerability, RP2D, efficacy

FAQ

  • What is BGB-11417 (sonrotoclax)? BGB-11417, also called sonrotoclax, is a novel Bcl-2 inhibitor. It is a type of drug that targets a protein involved in cancer cell survival. Researchers are studying it as a potential treatment for various blood cancers.
  • What types of blood cancers are being studied with BGB-11417? The clinical trials are investigating BGB-11417 for several blood cancers, including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), multiple myeloma (MM), and myeloid malignancies like acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
  • How is BGB-11417 being administered in these trials? BGB-11417 is being studied both as a single agent (monotherapy) and in combination with other drugs. It is given orally as a film-coated tablet. The trials are testing different doses and schedules to determine the optimal way to give the medication.
  • What are the main goals of these clinical trials? The primary objectives of these trials are to evaluate the safety and tolerability of BGB-11417, determine the appropriate dosing, and assess its effectiveness in treating various blood cancers. Researchers are measuring outcomes like overall response rates, progression-free survival, and overall survival.
  • Are there any specific patient groups being targeted in these studies? Yes, the trials are focusing on specific patient populations. For example, some studies are looking at patients with relapsed or refractory disease, meaning their cancer has returned or did not respond to previous treatments. Other trials are targeting newly diagnosed patients or those with specific genetic markers like t(11;14) in multiple myeloma.

Ongoing Clinical Trials on N-[4-({[(1R,4R)-4-Hydroxy-4-Methylcyclohexyl]Methyl}Amino)-3- Nitrobenzene-1-Sulfonyl]-4-(2-{(2S)-2-[2-(Propan-2-Yl)Phenyl]Pyrrolidin1-Yl}-7-Azaspiro[3.5]Nonan-7-Yl)-2-[(1H-Pyrrolo[2,3-B]Pyridin-5- Yl)Oxy]Benzamide

  • Study of sonrotoclax plus obinutuzumab or rituximab compared to venetoclax plus rituximab in patients with relapsed or refractory chronic lymphocytic leukemia

    Recruiting

    3 1 1 1
    Investigated drugs:
    Austria Belgium Czechia Denmark France Germany +6

  • Study of BGB-16673 in combination with drug therapy for patients with relapsed or refractory B-cell malignancies

    Recruiting

    1 1 1 1
    Investigated drugs:
    Germany Italy Poland

  • A study comparing BGB-11417 and zanubrutinib with venetoclax and acalabrutinib for patients with previously untreated chronic lymphocytic leukemia

    Recruiting

    3 1 1 1
    Investigated drugs:
    Czechia France Germany Italy The Netherlands Poland +3

  • Safety Study of Sonrotoclax and Zanubrutinib for Patients with Untreated Chronic Lymphocytic Leukemia

    Recruiting

    1 1 1
    Investigated drugs:
    France

  • Study on the Effectiveness and Safety of Sonrotoclax and Zanubrutinib for Adults with Relapsed or Refractory Mantle Cell Lymphoma

    Recruiting

    3 1
    Investigated diseases:
    Investigated drugs:
    Austria France Germany Italy Poland Spain

  • Study of BGB-11417 and Azacitidine for Patients with Myeloid Malignancies (AML, MDS, MDS/MPN)

    Recruiting

    1 1 1 1
    Investigated drugs:
    France Germany Italy Spain

  • Study on the Safety and Effectiveness of BGB-11417 Alone and with Dexamethasone, Carfilzomib, Daratumumab, or Pomalidomide for Patients with Relapsed or Refractory Multiple Myeloma

    Recruiting

    1 1 1 1
    Investigated drugs:
    France Germany Greece Italy Spain

  • Study on Zanubrutinib, Tislelizumab, and Sonrotoclax for Patients with Richter Transformation (a type of lymphoma)

    Recruiting

    2 1 1
    Investigated drugs:
    Austria Denmark Germany

  • Evaluating Sonrotoclax Alone and Combined with Zanubrutinib for Patients with Previously Untreated or Relapsed/Refractory Waldenström Macroglobulinemia

    Not recruiting

    2 1 1
    Investigated diseases:
    Investigated drugs:
    France Greece Italy Spain

  • Study on the Effectiveness and Safety of Sonrotoclax and Zanubrutinib for Adults with Untreated Chronic Lymphocytic Leukemia

    Not recruiting

    2 1 1 1
    Investigated diseases:
    Investigated drugs:
    Italy Poland Spain

Glossary

  • Bcl-2 inhibitor: A type of drug that blocks the action of the Bcl-2 protein, which helps cancer cells survive. By inhibiting Bcl-2, these drugs aim to promote cancer cell death.
  • Chronic lymphocytic leukemia (CLL): A type of blood cancer that affects white blood cells called lymphocytes. It typically progresses slowly and is more common in older adults.
  • Mantle cell lymphoma (MCL): A rare type of non-Hodgkin lymphoma that affects white blood cells called B lymphocytes. It often grows and spreads quickly.
  • Multiple myeloma (MM): A cancer of plasma cells, which are a type of white blood cell that normally produces antibodies. It can cause bone damage, kidney problems, and other complications.
  • Myeloid malignancies: A group of blood cancers that affect the myeloid cells, which include red blood cells, platelets, and certain types of white blood cells.
  • Acute myeloid leukemia (AML): A fast-growing cancer of the blood and bone marrow that affects myeloid cells. It requires prompt treatment.
  • Myelodysplastic syndromes (MDS): A group of disorders where the bone marrow doesn't produce enough healthy blood cells. It can sometimes progress to AML.
  • Relapsed/refractory: Refers to cancer that has returned after treatment (relapsed) or did not respond to treatment (refractory).
  • Overall response rate (ORR): The percentage of patients whose cancer shrinks or disappears after treatment.
  • Progression-free survival (PFS): The length of time during and after treatment that a patient lives without their cancer getting worse.
  • Overall survival (OS): The length of time from the start of treatment that patients are still alive.
  • Pharmacokinetics (PK): The study of how a drug moves through the body, including how it's absorbed, distributed, metabolized, and excreted.
  • Dose-limiting toxicity (DLT): Side effects that are severe enough to prevent increasing the dose of a drug in a clinical trial.
  • Maximum tolerated dose (MTD): The highest dose of a drug that can be given without causing unacceptable side effects.
  • Recommended Phase 2 dose (RP2D): The dose of a drug determined to be appropriate for further testing in Phase 2 clinical trials, based on safety and efficacy data from earlier studies.

References

  1. http://clinicaltrials.eu/trial/study-of-bgb-11417-for-patients-with-relapsed-or-refractory-mantle-cell-lymphoma/
  2. http://clinicaltrials.eu/trial/study-comparing-sonrotoclax-and-zanubrutinib-with-venetoclax-and-obinutuzumab-for-patients-with-untreated-chronic-lymphocytic-leukemia/
  3. http://clinicaltrials.eu/trial/study-on-zanubrutinib-tislelizumab-and-sonrotoclax-for-patients-with-richter-transformation-a-type-of-lymphoma/
  4. http://clinicaltrials.eu/trial/study-on-the-safety-and-effectiveness-of-bgb-11417-alone-and-with-dexamethasone-carfilzomib-daratumumab-or-pomalidomide-for-patients-with-relapsed-or-refractory-multiple-myeloma/
  5. http://clinicaltrials.eu/trial/study-of-bgb-11417-and-azacitidine-for-patients-with-myeloid-malignancies-aml-mds-mds-mpn/