What Is Monalizumab?
Monalizumab is an investigational drug being studied primarily for various types of cancer. It is a type of monoclonal antibody, specifically an anti-NKG2A antibody. NKG2A is a protein found on the surface of certain immune cells, such as natural killer (NK) cells and T cells. When NKG2A binds to another protein called HLA-E, it acts as a "brake," preventing these immune cells from attacking cancer cells.
By blocking NKG2A, Monalizumab aims to release this brake, allowing NK cells and T cells to better recognize and destroy cancer cells. This mechanism of action is being investigated in clinical trials to determine its safety and effectiveness in treating different cancers, often in combination with other anti-cancer therapies.
Uses and Conditions Under Study
Monalizumab is currently being investigated in 21 clinical trials involving a total of 4,199 participants. These studies began in 2015, with the latest trial expected to conclude in 2025. The drug is being explored for its potential to treat a range of cancers, often in combination with other immunotherapies or chemotherapy.
- Lung Cancers: Monalizumab is being studied for Non-small Cell Lung Cancer in 3 trials and Extensive Stage Lung Small Cell Carcinoma in 1 trial. Lung cancer is a leading cause of cancer-related death, and therapies like Monalizumab aim to enhance the immune system's ability to fight these tumors.
- Gastrointestinal Cancers: This includes Adenocarcinoma of the Esophagus (1 trial), Adenocarcinoma of the Gastroesophageal Junction (1 trial), and dMMR Colorectal Cancer (1 trial). Defective DNA mismatch repair (dMMR) status, often seen in colorectal cancer, indicates that these tumors can be highly responsive to immunotherapy.
- Other Solid Tumors: Monalizumab is also being investigated for Advanced Solid Tumors (1 trial), Advanced or Metastatic Hematological or Solid Tumor (1 trial), Breast Cancer (1 trial), and Early-stage cancers (1 trial). These studies aim to understand the drug's effectiveness across a broader spectrum of tumor types.
- Hematological Cancers: Chronic Lymphocytic Leukemia is another condition under study, with 1 trial exploring the potential benefits of Monalizumab in this blood cancer.
Dosing
Monalizumab is typically administered intravenously (into a vein) as an infusion. It has been studied in various dosing regimens, often in combination with other anti-cancer drugs like Durvalumab or Cetuximab. The specific dose and frequency can vary depending on the trial and the type of cancer being studied.
Some of the investigated dosing schedules for Monalizumab include:
- 750 mg every two weeks (Q2W), often combined with Durvalumab 1500 mg every four weeks (Q4W).
- Lower doses such as 22.5 mg, 75 mg, or 225 mg every two weeks have also been explored in dose-escalation studies.
- In some trials, Monalizumab 750 mg has been given every four weeks (Q4W).
- Weight-based dosing has also been investigated, with doses of 1 mg/kg, 2 mg/kg, and 4 mg/kg studied in early-phase trials, with 2 mg/kg identified as a recommended Phase 2 dose.
- Monalizumab has also been studied in combination with trastuzumab or with Cetuximab 400 mg/m^2.
These various dosing strategies are part of ongoing research to determine the most effective and safest way to use Monalizumab for different cancer types.
Side Effects
In a clinical trial involving 246 patients treated with Monalizumab, the most frequently reported side effects included skin conditions, fatigue, and gastrointestinal issues. It is important to compare these rates to those experienced by patients receiving a placebo to understand the drug's specific impact.
- Dermatitis acneiform was reported in 32.5% of patients taking Monalizumab, compared to 34.4% of patients on placebo.
- Rash occurred in 22.8% of patients on Monalizumab, while 22.1% of patients on placebo experienced rash.
- Fatigue was observed in 19.5% of patients receiving Monalizumab, compared to 16.4% of patients on placebo.
- Hypomagnesaemia (low magnesium levels) affected 17.1% of Monalizumab patients, versus 16.4% of placebo patients.
- Constipation was reported in 13.4% of patients taking Monalizumab, compared to 9.0% of patients on placebo.
- Anemia occurred in 13.4% of patients on Monalizumab, versus 12.3% of patients on placebo.
- Nausea was experienced by 10.6% of Monalizumab patients, which was lower
Currently Recruiting Trials
Monalizumab is currently being investigated in several clinical trials for various conditions, offering potential new treatment options. These studies aim to understand how Monalizumab works, often in combination with other therapies, and to evaluate its safety and effectiveness for patients.
One notable study, NCT06769126, is a Phase 2 trial sponsored by the SWOG Cancer Research Network. Titled "Using Biomarker Tests to Select and Test New, Personalized Treatments for Extensive Stage Small Cell Lung Cancer, PRISM Study," it is designed to enroll up to 900 participants. This trial investigates how biomarker tests can guide personalized treatment for extensive stage small cell lung cancer (ES-SCLC). Monalizumab is being tested in combination with durvalumab in one of the study's treatment arms.
For patients with non-muscle-invasive bladder cancer, a Phase 2 study (NCT06503614) is recruiting 60 participants. Sponsored by John Sfakianos, this trial evaluates durvalumab plus Monalizumab in patients with BCG-unresponsive or BCG-exposed non-muscle-invasive bladder cancer, including those with carcinoma in situ (CIS) or high-grade papillary urothelial cancer.
Another Phase 2 trial, NCT05903092, focuses on small cell lung cancer (SCLC). Sponsored by Hirva Mamdani, this study, known as MOZART, aims to enroll 84 participants across two cohorts: one for extensive-stage SCLC and another for limited-stage SCLC. In both cohorts, Monalizumab is combined with durvalumab and a platinum-etoposide chemotherapy regimen.
In the realm of non-small cell lung cancer (NSCLC), AstraZeneca is sponsoring a large Phase 2 trial (NCT05061550) with an enrollment target of 630 participants. This study assesses various perioperative treatment combinations for resectable NSCLC, including an arm that combines Monalizumab with durvalumab and platinum doublet chemotherapy.
Finally, a Phase 2 study (NCT06892223) sponsored by Istituto Clinico Humanitas is recruiting 42 participants to evaluate Monalizumab in a different context. This trial investigates the anti-NKG2A monoclonal antibody in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who are undergoing haploidentical stem cell transplantation.
Where to Participate
Clinical trials involving Monalizumab are accessible across a broad geographic area, with study sites established in 35 states across the United States. In total, there are 156 sites located in 138 cities, providing numerous opportunities for eligible patients to participate.
Some of the cities with the highest number of recruiting sites include:
- Des Moines, Iowa (4 sites)
- Fargo, North Dakota (3 sites)
- Grosse Pointe Woods, Michigan (3 sites)
- Dayton, Ohio (3 sites)
- Nashville, Tennessee (3 sites)
- Warren, Michigan (3 sites)
- Greenville, South Carolina (3 sites)
- Houston, Texas (3 sites)
- Baltimore, Maryland (3 sites)
- Portland, Oregon (2 sites)
Eligibility criteria for these trials generally require participants to be between 18 and 99 years of age. All genders are welcome to participate, but these studies are not open to healthy volunteers or children, as they focus on specific patient populations with existing medical conditions.
Development Timeline
The journey of Monalizumab in clinical development began on September 23, 2015, with its first clinical trial. Initially, the drug was explored for conditions such as irritable bowel syndrome with constipation (IBS-C) and hyperphosphatemia, indicating a broad early interest in its therapeutic potential. However, the development pipeline quickly expanded and shifted focus.
Over time, Monalizumab's investigation broadened significantly into oncology. Early sponsors like MedImmune LLC, AstraZeneca, and Innate Pharma played key roles in driving its development. The drug progressed through various phases, with two Phase 1 trials, four Phase 1/Phase 2 trials, and a substantial thirteen Phase 2 trials, demonstrating a steady advancement in understanding its effects. Currently, two Phase 3 trials are also underway, indicating a move towards late-stage evaluation.
The scope of conditions under investigation for Monalizumab has expanded dramatically to include a wide array of cancers. These now encompass extensive stage small cell lung cancer, non-muscle-invasive bladder cancer, non-small cell lung cancer, acute myeloid leukemia, myelodysplastic syndrome, breast cancer, head and neck neoplasms, and colorectal cancer, among others. This broad exploration highlights Monalizumab's potential across diverse cancer types. To date, a total of 21 clinical trials have been initiated, involving 4,199 participants, with the latest trial projected to conclude in August 2025.