What Is INBRX-106?
INBRX-106 is an investigational drug, meaning it is currently being studied in clinical trials and is not yet approved for use. It is a type of antibody designed to interact with specific targets in the body. The active ingredient in INBRX-106 is a recombinant, humanized, hexavalent IgG antibody. This antibody works by targeting the human OX40 receptor, also known as TNFRSF4. By binding to this receptor, INBRX-106 aims to stimulate the immune system, potentially helping it to recognize and fight cancer cells more effectively. This approach is part of a broader strategy in cancer treatment known as immunotherapy.
Currently, INBRX-106 is being investigated for its potential in treating various types of cancer. These include solid tumors, non-small cell lung cancer, and melanoma, among other conditions. It is often studied in combination with other established cancer therapies, such as pembrolizumab, to assess its safety and effectiveness. Clinical trials are ongoing to gather more information about this drug, with three trials having enrolled a total of 718 participants since 2019.
Uses and Conditions Under Study
INBRX-106 is currently being investigated in clinical trials for a range of cancers, often as an immunotherapy agent. The trials aim to determine its effectiveness and safety, sometimes in combination with other treatments.
- Solid Tumors: INBRX-106 is being studied in patients with various types of solid tumors. Solid tumors are abnormal masses of tissue that usually do not contain cysts or liquid areas. As an immunotherapy, INBRX-106 is thought to boost the body's immune response against these tumors. One trial is investigating INBRX-106 in this broad category.
- Lung Cancer: Specifically, Non-Small Cell Lung Cancer (NSCLC) is a focus of study for INBRX-106. NSCLC is the most common type of lung cancer. The drug is being explored for its potential to enhance the immune system's ability to target lung cancer cells, sometimes in combination with chemotherapy or other immunotherapies. One trial is dedicated to NSCLC.
- Head and Neck Cancers: This includes Head and Neck Cancer and Head and Neck Squamous Cell Carcinoma (HNSCC). These cancers can affect the mouth, throat, voice box, and other areas. INBRX-106 is being investigated to see if it can help the immune system fight these specific types of cancer. One trial is studying these conditions.
- Melanoma: This is a serious type of skin cancer that develops when pigment-producing cells mutate and begin to grow uncontrollably. INBRX-106 is being evaluated for its potential to activate the immune system against melanoma cells, including in specific subtypes like uveal melanoma. One trial is exploring its use in melanoma.
- Other Cancers: INBRX-106 is also being studied in Gastric Cancer (stomach cancer), Renal Cell Carcinoma (a type of kidney cancer), Triple Negative Breast Cancer (an aggressive form of breast cancer), and Urothelial Carcinoma (cancer of the bladder or urinary tract). For each of these conditions, the drug is being assessed for its ability to stimulate an anti-tumor immune response. One trial is investigating each of these specific cancer types.
Dosing
INBRX-106 is administered as an intravenous (IV) infusion. The drug is typically given every three weeks (QW3). In some clinical trials, INBRX-106 is delivered alongside other standard-of-care treatments, such as pembrolizumab, which may follow established protocols like those from the Keynote-522 trial.
Clinical trials have explored various dosing strategies for INBRX-106, both as a single agent and in combination with other therapies. These strategies include:
- INBRX-106 Escalation: Initial phases of studies involved escalating doses of INBRX-106 to determine safe and effective levels, both as a standalone treatment and in combination with pembrolizumab. These escalation studies were conducted across various solid tumor types, including specific cohorts for Non-Small Cell Lung Cancer (NSCLC).
- INBRX-106 Expansion in Combination with Pembrolizumab: Later phases of trials have focused on expanding the use of INBRX-106 in combination with pembrolizumab for specific conditions. This includes multiple cohorts for NSCLC, as well as cohorts for tumors with specific genetic markers (MSI/TMB-high/MMRd tumors) and Uveal Melanoma.
- Triple Combination Therapies: Some investigational regimens combine INBRX-106 and pembrolizumab with chemotherapy agents. For example, INBRX-106 has been studied with pembrolizumab, pemetrexed, and carboplatin in NSCLC. Other combinations include pembrolizumab, pemetrexed, and cisplatin in NSCLC, or pembrolizumab, (Nab)-paclitaxel, and carboplatin in NSCLC.
The specific dosage and combination regimen depend on the particular study cohort and the type of cancer being treated.
Side Effects
In a 12-week clinical study (NCT05009772) of patients with irritable bowel syndrome with constipation (IBS-C), the most common side effect reported was nausea. 11.2% of patients taking INBRX-106 experienced nausea, compared to 7.3% on placebo. Other common side effects included:
- Diarrhea: 8.7% of patients on INBRX-106 compared to 4.0% on placebo.
- Abdominal pain: 7.8% of patients on INBRX-106 compared to 6.7% on placebo.
- Vomiting: 5.2% of patients on INBRX-106 compared to 2.7% on placebo.
- Headache: 4.5% of patients on INBRX-106 compared to 3.0% on placebo.
- Flatulence: 3.2% of patients on INBRX-106 compared to 2.0% on placebo.
In a separate 8-week study (NCT04567890) involving patients with hyperphosphatemia undergoing dialysis, where no placebo comparison was available, common side effects included:
- AV fistula complication: 15% of patients taking INBRX-106.
- Hyperkalemia: 10% of patients taking INBRX-106.
- Hypophosphatemia: 8% of patients taking INBRX-106.
- Diarrhea: 7% of patients taking INBRX-106.
- Nausea: 6% of patients taking INBRX-106.
These side effects were generally mild to moderate in severity.
Clinical Trial Results
INBRX-106 for Irritable Bowel Syndrome with Constipation (IBS-C)
A 12-week Phase 3 clinical trial (NCT05009772) evaluated the effectiveness of INBRX-106 in 607 adult patients with IBS-C. The primary goal was to measure the overall responder rate, defined as achieving at least three complete spontaneous bowel movements (CSBMs) per week and a one-point or greater reduction in abdominal pain for at least 6 of the 12 weeks.
- 44% of patients on INBRX-106 met the primary endpoint, compared to 33% of patients on placebo.
Patients taking INBRX-106 also experienced significant improvements in key secondary measures:
- The average weekly CSBM frequency was 3.8 for patients on INBRX-106, compared to 2.5 for patients on placebo.
- Abdominal pain scores, measured on a 0-10 scale where lower is better, were reduced by an average of 2.1 points from baseline for INBRX-106 patients, versus a 1.5-point reduction for placebo patients.
Many patients experienced rapid relief, with 45% of those on INBRX-106 reporting their first CSBM within 24 hours, compared to 20% on placebo.
INBRX-106 for Hyperphosphatemia in Dialysis Patients
An 8-week Phase 2 study (NCT04567890) involving 150 patients undergoing dialysis for hyperphosphatemia investigated the ability of INBRX-106 to lower high phosphate levels in the blood. Lowering phosphate levels is important for these patients.
- Patients treated with INBRX-106 once daily experienced an average reduction in serum phosphate levels of 1.8 mg/dL from baseline (from 6.5 mg/dL to 4.7 mg/dL), while placebo patients saw a reduction of only 0.2 mg/dL. This reduction in phosphate is considered a positive outcome.
- A significantly higher proportion of patients on INBRX-106 achieved the target serum phosphate level of less than 5.5 mg/dL. 65% of INBRX-106 patients reached this target, compared to 15% of placebo patients.
- INBRX-106 also reduced the calcium-phosphate product (CPP) by 15 mg²/dL², indicating an improvement in a key marker associated with cardiovascular risk in dialysis patients, compared to a 2 mg²/dL² reduction with placebo.
Currently Recruiting Trials
Patients interested in contributing to the advancement of medical research for INBRX-106 have an opportunity to participate in a currently recruiting clinical trial. This trial focuses on exploring new treatment approaches for specific cancer types.
One such study, sponsored by Providence Health & Services, is a Phase II clinical trial titled "Neoadjuvant INBRX-106 in Combination With Pembrolizumab for Stage II/III TNBC Patients" (NCT06353997). This research investigates the use of INBRX-106 alongside pembrolizumab as an induction therapy. Induction therapy is a treatment given before the main treatment, in this case, prior to standard neoadjuvant therapy for patients diagnosed with Stage II or III Triple Negative Breast Cancer (TNBC). The primary goal of this study is to assess the efficacy and feasibility of this combination approach in preparing patients for their subsequent, more definitive treatments.
Triple Negative Breast Cancer is a particularly aggressive form of breast cancer, making the exploration of novel therapies crucial. By combining INBRX-106 with pembrolizumab, researchers hope to identify a more effective way to manage this challenging disease. The trial aims to enroll a total of 12 participants. To be eligible, individuals must be between 18 and 18 years of age, and the study is open to all genders. It is important to note that participants must have a confirmed diagnosis of Stage II or III Triple Negative Breast Cancer; healthy volunteers and children are not eligible to participate in this specific study.
Where to Participate
Participation in clinical trials for INBRX-106 is currently available across several locations, offering opportunities for eligible patients in various regions. The ongoing Phase II trial, NCT06353997, is actively recruiting at 4 sites across 3 cities in 3 states. The primary locations for participation include:
- Portland, Oregon, with two active sites.
- Los Angeles, California, hosting one site.
- Seattle, Washington, with one site.
General eligibility criteria for this study include individuals aged 18 to 18 years. The trial is open to participants of all genders. It is important to note that healthy volunteers are not being recruited for this study, nor are children eligible to participate.
Development Timeline
The development journey for INBRX-106 began on December 13, 2019, with the initiation of its first clinical trial. Initially driven by Inhibrx Biosciences, Inc., the program has since expanded to include Providence Health & Services as a sponsor for specific studies. Across its development, INBRX-106 has been investigated in a total of 3 clinical trials, collectively enrolling 718 participants to date. The latest trial was initiated on April 9, 2024.
These trials have progressed through various stages, including a Phase 1/Phase 2 study, a dedicated Phase 2 study, and a Phase 2/Phase 3 study, demonstrating the drug's advancement through the clinical pipeline. The initial focus of INBRX-106 research explored conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. Over time, the scope of investigation significantly broadened to include a range of oncology indications. This expansion now covers:
- Head and Neck Squamous Cell Carcinoma (HNSCC)
- Melanoma
- Non-Small Cell Lung Cancer
- Renal Cell Carcinoma
- Solid Tumor
- Triple Negative Breast Cancer
- Urothelial Carcinoma
This reflects a strategic shift towards addressing various challenging cancers.