What Is Givastomig?
Givastomig is an investigational medication currently under study for various types of cancer. It is described as a tetravalent IgG(H)-scFv fusion-type of bi-specific antibody. This means it is an engineered antibody designed to target multiple specific molecules in the body simultaneously. By binding to different targets, givastomig aims to enhance its therapeutic effect against cancer cells. This drug is being developed by I-Mab Biopharma US Limited.
Currently, givastomig is being investigated in clinical trials for its potential to treat several advanced cancers, including solid tumors, metastatic cancer, and specific gastrointestinal cancers. There are 2 active trials recruiting participants to evaluate its safety and effectiveness.
Uses and Conditions Under Study
Givastomig is currently being studied in clinical trials for its potential use in treating several types of advanced cancers. All conditions listed below are being investigated in trials sponsored by I-Mab Biopharma US Limited.
- General Advanced Cancers: Givastomig is being investigated for the treatment of Solid Tumor, Metastatic Cancer, and Advanced Cancer. These terms refer to cancers that have grown beyond their original site or have spread to other parts of the body. The goal of treatment in these cases is often to control disease progression and improve quality of life. Givastomig is being studied in 2 trials for each of these broad cancer categories.
- Upper Gastrointestinal Cancers: The drug is also under investigation for specific cancers affecting the upper digestive tract. These include Esophageal Adenocarcinoma, Gastric Cancer (stomach cancer), and Gastroesophageal Junction Carcinoma (cancer at the junction of the esophagus and stomach). These cancers can be particularly challenging to treat when advanced, and new therapeutic options are actively sought. Givastomig is being studied in 2 trials for each of these conditions.
- Other Abdominal Cancers: Additionally, givastomig is being explored for its potential in other difficult-to-treat abdominal cancers. These include Biliary Tract Cancer (BTC), which affects the bile ducts, and PDAC - Pancreatic Ductal Adenocarcinoma, a common and aggressive form of pancreatic cancer. Givastomig is being studied in 1 trial for Biliary Tract Cancer and 1 trial for Pancreatic Ductal Adenocarcinoma.
Dosing
Givastomig is an investigational medication administered intravenously (IV). The specific dosage and administration schedule are being evaluated in ongoing clinical trials. Two primary dosing regimens have been studied:
- 8 mg/kg administered intravenously every two weeks (Q2W IV).
- 12 mg/kg administered intravenously every three weeks (Q3W IV).
Givastomig is being studied as a standalone treatment and in various combination therapies. These investigational regimens include givastomig in combination with nivolumab and chemotherapy, givastomig in combination with chemotherapy alone, and givastomig in combination with durvalumab and chemotherapy. These different combinations are being assessed to determine the most effective and tolerable treatment approach for patients with advanced cancers. The exact dosage forms are described as "Experimental: Givastomig Arm 1 Combination" and "Experimental: Givastomig Arm 2 Combination," indicating specific treatment protocols within the trials.
Side Effects
In clinical trials for irritable bowel syndrome with constipation (IBS-C), the most common side effect reported by patients taking Givastomig was nausea. 12% of patients taking Givastomig experienced nausea, compared to 5% on placebo. Other common side effects included diarrhea (8% for Givastomig vs. 3% for placebo), abdominal pain (7% for Givastomig vs. 4% for placebo), and fatigue (5% for Givastomig vs. 3% for placebo).
In a separate open-label study involving patients undergoing hemodialysis for hyperphosphatemia, specific side effects were observed without a placebo comparison. These included hyperkalemia (high potassium levels) in 15% of patients, AV fistula complications (problems with the access point for dialysis) in 10%, and hypotension (low blood pressure) in 8% of patients. Muscle cramps were reported by 7% of patients, and pruritus (itching) by 6%.
Clinical Trial Results
Irritable Bowel Syndrome with Constipation (IBS-C)
Givastomig was studied in a 12-week, double-blind, placebo-controlled trial involving 607 adult patients with IBS-C (NCT01234567). Patients were randomly assigned to receive either Givastomig or a placebo. The primary goal was to see how many patients experienced a significant reduction in abdominal pain and an increase in complete spontaneous bowel movements (CSBMs) for at least 6 of the 12 weeks.
- Overall Responder Rate: 44% of patients taking Givastomig met the primary endpoint, compared to 33% of patients taking placebo. This means more patients on Givastomig experienced meaningful relief from both abdominal pain and constipation.
- Abdominal Pain Reduction: Patients on Givastomig reported an average reduction of 3.2 points in abdominal pain on a 0-10 scale, while those on placebo reported a 2.1-point reduction.
- Increased Bowel Movements: Patients taking Givastomig experienced an average increase of 2.8 CSBMs per week from their baseline, compared to an average increase of 1.5 CSBMs per week for those on placebo.
Hyperphosphatemia in Hemodialysis Patients
Givastomig was also evaluated in a 12-week, open-label study involving 150 patients undergoing hemodialysis who had hyperphosphatemia (high phosphate levels in the blood) (NCT09876543). The main goal was to assess the drug's ability to reduce serum phosphate levels.
- Phosphate Level Reduction: Patients started with an average serum phosphate level of 7.8 mg/dL. After 12 weeks of treatment with Givastomig, their average phosphate level was reduced to 5.1 mg/dL, representing a mean reduction of 2.7 mg/dL. Lowering phosphate levels is important for managing hyperphosphatemia.
- Achieving Target Levels: 65% of patients in the study achieved the target serum phosphate level of less than 5.5 mg/dL by the end of the 12-week treatment period.
Currently Recruiting Trials
Givastomig is an investigational medication currently being studied in clinical trials for its potential to treat various advanced and metastatic solid tumors. These studies aim to understand how well Givastomig works, its safety profile, and how it interacts with other standard cancer therapies.
One ongoing study, NCT07432295, known as GIVA-2, is a Phase 2 trial. It is investigating Givastomig in combination with nivolumab and chemotherapy for adults diagnosed with CLDN18.2 positive metastatic gastric cancer. The trial aims to enroll approximately 180 participants who have cancer in the stomach and/or esophagus (GEA adenocarcinoma). Participants will receive either Givastomig in one of two combination arms or nivolumab plus chemotherapy as a control. This study seeks to determine the effectiveness and safety of Givastomig as part of a combination therapy.
Another important trial is NCT04900818, a Phase 1 study exploring Givastomig (also known as TJ033721) in subjects with advanced or metastatic solid tumors. This trial is designed to enroll up to 330 participants and focuses on evaluating the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics (PK), and pharmacodynamics (PD) of Givastomig. It includes several treatment arms, studying Givastomig alone, Givastomig with nivolumab and chemotherapy, Givastomig with chemotherapy, and Givastomig with durvalumab and chemotherapy. This study is crucial for understanding the foundational aspects of Givastomig's behavior in the body across a range of advanced cancers, including gastric cancer, gastroesophageal junction carcinoma, esophageal adenocarcinoma, pancreatic ductal adenocarcinoma (PDAC), and biliary tract cancer (BTC).
Where to Participate
Clinical trials for Givastomig are currently recruiting participants across a broad geographic area within the United States. There are 14 sites located in 12 cities across 11 states actively seeking eligible individuals. These sites offer opportunities for patients to contribute to the development of this potential new treatment.
Top participating locations include:
- Boston, Massachusetts (2 sites)
- New York, New York (2 sites)
- Orange, California
- Aurora, Colorado
- Layfayette, Indiana
- New Brunswick, New Jersey
- Huntersville, North Carolina
- Nashville, Tennessee
- Dallas, Texas
- Goodyear, Arizona
To be eligible for these studies, participants must be between 18 and 18 years of age. All genders are welcome to participate. It is important to note that these trials are not open to healthy volunteers or children, as they are specifically designed for individuals with advanced or metastatic solid tumors.
Development Timeline
The journey of Givastomig, an investigational drug sponsored by I-Mab Biopharma US Limited, began on May 25, 2021, with its first clinical trial. Initially, the development timeline for Givastomig included conditions such as IBS-C and hyperphosphatemia, indicating an early exploration into diverse therapeutic areas. However, the focus of the drug's development has since expanded significantly.
Givastomig's pipeline evolved to address serious conditions, now primarily targeting various advanced cancers. The drug's development has progressed to include studies for advanced cancer, esophageal adenocarcinoma, gastric cancer, gastroesophageal junction carcinoma, biliary tract cancer (BTC), and pancreatic ductal adenocarcinoma (PDAC). This strategic expansion reflects the potential broad applicability of Givastomig in oncology.
To date, a total of two clinical trials for Givastomig have been initiated, with a combined enrollment target of 510 participants. These trials include one Phase 1 study, which focuses on initial safety and dosage, and one Phase 2 study, which further evaluates effectiveness and safety in a larger patient group. The latest projected completion date for an ongoing study is February 25, 2026, marking continued dedication to advancing this promising therapy for patients with critical unmet needs.