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BI-1607

BI-1607 is a promising new drug being investigated for patients with HER2-positive cancers, including breast cancer and gastric cancer. This monoclonal antibody targets CD32b (Fc Gamma Receptor IIB) and is designed to enhance the effectiveness of trastuzumab (Herceptin), a standard treatment for HER2-positive cancers. While trastuzumab has significantly improved survival rates, many patients develop resistance over time, leading to disease progression. Clinical trials are currently underway to evaluate how BI-1607, when combined with trastuzumab, might overcome this resistance and improve outcomes for patients whose cancers have progressed after standard therapy.

Table of Contents

What is BI-1607?

BI-1607 is a new experimental drug being studied for treating certain types of cancer. Specifically, it is a human immunoglobulin G1 (IgG1) monoclonal antibody that targets a protein called CD32b, also known as Fc Gamma Receptor IIB. This medication is currently being investigated in clinical trials and is not yet approved for general use.[1]

The drug is specifically designed to be used in combination with another medication called trastuzumab (brand name: Herceptin). Trastuzumab is an established treatment for certain cancers, but many patients develop resistance to it over time. BI-1607 aims to enhance trastuzumab’s effectiveness and overcome this resistance problem.[1]

How BI-1607 Works

BI-1607 has been engineered to target and block CD32b (Fc Gamma Receptor IIB), which is a protein found on certain immune cells. This receptor is thought to play a role in how cancer cells become resistant to treatments like trastuzumab.[1]

By blocking CD32b, BI-1607 aims to:

  • Enhance the effectiveness of trastuzumab treatment
  • Help overcome resistance to trastuzumab in patients whose cancer has stopped responding to this treatment
  • Potentially improve survival rates for patients with HER2-positive cancers

The drug is specifically designed as an Fc-engineered antibody, which means its structure has been modified to improve its function and interaction with the immune system.[1]

Target Conditions

BI-1607 is being studied for the treatment of HER2-positive advanced solid tumors. HER2 (Human Epidermal Growth Factor Receptor 2) is a protein that promotes cancer cell growth. When a cancer has higher than normal levels of HER2, it is called “HER2-positive.”[1]

Specifically, the clinical trials are focusing on these conditions:

  • HER2-positive breast cancer – Including locally advanced and metastatic (spread to other parts of the body) forms
  • HER2-positive gastric (stomach) cancer – Including metastatic cases
  • Metastatic gastroesophageal junction adenocarcinoma – Cancer at the junction between the esophagus and stomach that has spread to other parts of the body

These types of cancer are chosen because they often respond initially to trastuzumab treatment but may develop resistance over time, creating a need for new approaches like BI-1607.[1]

Clinical Trial Information

BI-1607 is currently being studied in a Phase 1/2a clinical trial. This is an early-stage investigation to determine if the drug is safe and effective. The trial is described as “first-in-human,” meaning this is the first time the drug is being tested in people.[1]

The clinical trial has two main parts:

  • Phase 1: This initial phase focuses on finding the right dose of BI-1607 to use with trastuzumab. Researchers gradually increase the dose in different groups of patients to determine which dose is both safe and potentially effective. The main goal is to assess safety, tolerability, and determine the recommended Phase 2 dose (RP2D).[1]
  • Phase 2a: Once the appropriate dose is determined, the study expands to include two groups of 15 patients each:
    • One group with locally advanced or metastatic HER2-positive breast cancer
    • One group with HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma
    The goals of this phase are to gather more safety data and look for early signs that the treatment is working.[1]

This trial is specifically for patients whose cancer has progressed despite receiving standard treatments, representing an important potential option for those who have limited treatment alternatives.[1]

Treatment Administration

In the clinical trial, BI-1607 is administered through intravenous (IV) infusions – meaning it’s delivered directly into the bloodstream through a vein. These infusions are given every 3 weeks.[1]

The combination treatment includes:

  • BI-1607: Given at different doses during Phase 1 to determine the optimal amount. In Phase 2a, it is given at the recommended dose established during Phase 1.[1]
  • Trastuzumab (Herceptin): Administered at a loading dose of 8 mg/kg for the first infusion, followed by 6 mg/kg in subsequent infusions. Like BI-1607, trastuzumab is given every 3 weeks as an intravenous infusion.[1]

Patients in the trial receive regular monitoring to assess how their body responds to the treatment, including blood tests and imaging studies to track the cancer’s response.[1]

Safety and Effectiveness

As BI-1607 is still in early clinical trials, comprehensive information about its safety profile and effectiveness is not yet available. However, the clinical trial is designed to carefully monitor several important aspects:[1]

  • Safety monitoring: Researchers track all side effects (adverse events) and serious side effects, rating their severity according to established criteria (National Cancer Institute Common Terminology Criteria for Adverse Events).
  • Dose-limiting toxicities: The study identifies any side effects that are severe enough to limit the dose that can be given safely.
  • Pharmacokinetics: The study examines how the drug moves through the body, including how quickly it’s absorbed, distributed, and eliminated.
  • Immunogenicity: Researchers check whether the patient’s immune system develops antibodies against BI-1607, which could potentially reduce its effectiveness.
  • Receptor occupancy: The study measures how effectively BI-1607 binds to its target (CD32b) on B cells in the blood.

To evaluate whether the treatment is working, researchers will assess:[1]

  1. Objective response rate (ORR): The percentage of patients whose tumors shrink a meaningful amount
  2. Progression-free survival (PFS): How long patients live without their cancer getting worse
  3. Duration of response (DOR): How long any positive response to treatment lasts
  4. Overall survival (OS): How long patients live after starting treatment

Future Research

Beyond the basic safety and effectiveness evaluations, the clinical trial includes several exploratory research goals that may help improve future treatments:[1]

  • Investigating the levels of Fc receptors (including CD32b) and other immune markers in tumor samples to better understand how the drug works
  • Studying patients’ genetic profiles related to FcgammaR isoforms (variations in the receptors that BI-1607 targets) to see if certain genetic patterns might predict who will respond better to the treatment
  • Exploring relationships between BI-1607 concentration in the blood and treatment outcomes or side effects

This additional research may help identify which patients are most likely to benefit from BI-1607, potentially leading to more personalized treatment approaches in the future.[1]

Study Aspect Details
Drug Name BI-1607
Drug Type Human immunoglobulin G1 (IgG1) monoclonal antibody targeting CD32b (Fc Gamma Receptor IIB)
Combination Therapy BI-1607 + Trastuzumab (Herceptin)
Target Conditions HER2-positive advanced solid tumors including breast cancer, gastric cancer, and gastroesophageal junction adenocarcinoma
Trial Phase Phase 1/2a, first-in-human
Administration Intravenous infusions every 3 weeks
Phase 1 Goal Assess safety, tolerability, and determine recommended Phase 2 dose (RP2D)
Phase 2a Goal Collect additional safety data and detect early signs of clinical activity in specific cancer types
Target Patient Population Patients whose tumors have progressed after standard therapy
Primary Measurements Safety profile, dose-limiting toxicities, maximum tolerated dose
Secondary Measurements Pharmacokinetics, immunogenicity, receptor occupancy, and antitumor activity

FAQ

  • What is BI-1607 and how does it work? BI-1607 is a human immunoglobulin G1 (IgG1) monoclonal antibody that targets CD32b, also known as Fc Gamma Receptor IIB. It works by enhancing the effectiveness of existing cancer treatments, specifically trastuzumab (Herceptin). By targeting CD32b, BI-1607 aims to overcome resistance to trastuzumab and improve its cancer-fighting abilities in patients with HER2-positive tumors.
  • What types of cancer is BI-1607 being tested for? BI-1607 is currently being tested in clinical trials for HER2-positive advanced solid tumors, specifically focusing on HER2-positive breast cancer, metastatic breast cancer, HER2-positive gastric cancer, and metastatic gastroesophageal junction adenocarcinoma. These are cancers that have higher levels of a protein called HER2 on their cell surfaces.
  • How is BI-1607 administered to patients? BI-1607 is administered through intravenous (IV) infusions every 3 weeks. In the clinical trial, it is given in combination with trastuzumab, which is also administered intravenously. Trastuzumab is given at a dose of 8mg/kg for the first infusion and 6mg/kg in subsequent infusions every 3 weeks.
  • What phase of clinical testing is BI-1607 currently in? BI-1607 is currently in a Phase 1/2a clinical trial. The Phase 1 part focuses on dose escalation to assess safety and find the appropriate dosage. The Phase 2a part involves expanding the trial to more patients at the recommended dose to collect additional safety data and look for early signs of effectiveness in patients with specific HER2-positive cancers.
  • Who might benefit from the BI-1607 clinical trial? The clinical trial is designed for patients with HER2-positive advanced solid tumors whose cancer has progressed after standard therapy. This includes patients with locally advanced or metastatic HER2-positive breast cancer and those with HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma who have not responded adequately to existing treatments like trastuzumab alone.

Ongoing Clinical Trials on BI-1607

  • Study of BI-1607, Ipilimumab, and Pembrolizumab for Patients with Advanced Melanoma

    Not recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    Germany Spain

Glossary

  • HER2-positive: A type of cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2). This protein promotes the growth of cancer cells. HER2-positive cancers tend to be more aggressive but also respond to targeted treatments.
  • Monoclonal Antibody (mAb): A type of protein made in the laboratory that can bind to specific targets in the body. In cancer treatment, monoclonal antibodies can be designed to attach to specific proteins on cancer cells to help the immune system identify and destroy those cells.
  • CD32b (Fc Gamma Receptor IIB): A protein found on the surface of certain immune cells that can inhibit immune responses. In cancer treatment, blocking CD32b may help enhance the effectiveness of other treatments by preventing this inhibitory effect.
  • Trastuzumab (Herceptin): A monoclonal antibody used to treat HER2-positive breast and gastric cancers. It works by attaching to HER2 receptors on cancer cells, blocking them from receiving growth signals and flagging them for destruction by the immune system.
  • First-in-human (FIH): A term used to describe the first clinical trial of a new drug or treatment in human subjects, typically after laboratory and animal testing has been completed.
  • Dose Escalation: A process in clinical trials where the amount of drug given to participants is gradually increased to find the optimal dose that provides the desired effect with acceptable side effects.
  • Recommended Phase 2 Dose (RP2D): The dose of a drug determined from Phase 1 studies that is recommended for use in Phase 2 clinical trials. This dose balances effectiveness with an acceptable level of side effects.
  • Dose Limiting Toxicity (DLT): Side effects of a treatment that are severe enough to prevent an increase in dosage or require a dose reduction in a clinical trial.
  • Maximum Tolerated Dose (MTD): The highest dose of a drug or treatment that does not cause unacceptable side effects. Determining the MTD is often a goal of Phase 1 clinical trials.
  • Pharmacokinetics (PK): The study of how a drug moves into, through, and out of the body. This includes how the body absorbs, distributes, metabolizes, and excretes the drug.
  • Immunogenicity: The ability of a substance to provoke an immune response. In drug development, researchers monitor for unwanted immune responses (like antibodies) against the treatment itself.
  • Receptor Occupancy (RO): A measure of how much of a specific receptor is bound by a drug. Higher receptor occupancy often correlates with greater drug effect.
  • Objective Response Rate (ORR): The percentage of patients whose cancer shrinks or disappears after treatment. It's a measure used to evaluate how effective a cancer treatment is.
  • Progression-Free Survival (PFS): The length of time during and after treatment that a patient lives with cancer without it worsening. This is an important measure of a cancer treatment's effectiveness.
  • Duration of Response (DOR): The length of time from documented tumor response to disease progression. This measures how long a treatment continues to work in patients who respond.
  • Metastatic: Cancer that has spread from its original site to other parts of the body. Metastatic cancer is generally more difficult to treat than cancer that hasn't spread.
  • Adenocarcinoma: A type of cancer that forms in the glandular cells that line certain organs. Gastric adenocarcinoma starts in the glandular cells of the stomach lining.
  • Gastroesophageal Junction: The area where the esophagus (food pipe) meets the stomach. Cancers that develop in this region are called gastroesophageal junction adenocarcinomas.
  • Adverse Events (AEs): Any unfavorable and unintended sign, symptom, or disease associated with the use of a medical treatment. These may or may not be caused by the treatment itself.
  • Serious Adverse Events (SAEs): Adverse events that result in death, are life-threatening, require hospitalization, cause persistent or significant disability, or other important medical events that may jeopardize the patient.

References

  1. https://clinicaltrials.gov/study/NCT05555251