Nisevokitug

Drug Overview

Nisevokitug (also known by its developmental code JNJ-77365868) is an investigational, first-in-class monoclonal antibody designed to target and bind to the Cholecystokinin-2 Receptor (CCK2R). This receptor is frequently overexpressed in several types of difficult-to-treat solid tumors, particularly those of the gastrointestinal and endocrine systems, where it promotes tumor cell proliferation and survival.

In the clinical landscape of March 2026, Nisevokitug is recognized as a pioneer in the targeting of “orphan” G-protein coupled receptors (GPCRs) in oncology. While many therapies target common proteins like EGFR or HER2, nisevokitug is specifically engineered for patients whose tumors have been “primed” by high levels of CCK2R. By binding to this receptor, nisevokitug blocks the signaling of gastrin and cholecystokinin, effectively “starving” the tumor of the signals it uses to grow and potentially inducing immune-mediated cell death.

• Generic Name: Nisevokitug.
• Code Name: JNJ-77365868.
• Drug Class: Monoclonal Antibody; CCK2R-targeted Therapy.
• Mechanism: Competitive inhibition of the CCK2R receptor and potential induction of antibody-dependent cellular cytotoxicity (ADCC).
• Route of Administration: Intravenous (IV) infusion.
• FDA Approval Status: Investigational. As of March 2026, nisevokitug is not FDA-approved. It is currently being evaluated in Phase 1 and Phase 2 clinical trials for a variety of advanced solid tumors.

What Is It and How Does It Work? (Mechanism of Action)

Nisevokitug works by disrupting the “hormonal fuels” that certain tumors use to drive their aggressive behavior.

1. Targeting the CCK2R Receptor

The CCK2R receptor (also known as the Gastrin receptor) is normally found in the stomach and brain, where it manages acid secretion and digestion. However, in certain cancers, the tumor “hijacks” this receptor.

• Selective Binding: Nisevokitug binds to the extracellular portion of the CCK2R receptor with extremely high affinity.
• Ligand Blockade: This prevents natural hormones like gastrin from binding to the receptor. In gastrin-dependent tumors, this blockade can significantly slow or stop tumor growth.

2. Signal Transduction Interruption

Once nisevokitug binds to the receptor, it prevents the activation of several “downstream” growth pathways:

• MAPK and PI3K/AKT: These pathways are the “engines” of the cell; shutting them down forces the cancer cell into a state of metabolic stress or dormancy.
• Calcium Signaling: CCK2R activation usually causes a surge in internal cellular calcium, which promotes cell movement and metastasis. Nisevokitug helps keep these calcium levels in check.

3. Immune System Recruitment (ADCC)

As a monoclonal antibody, nisevokitug can also act as a “flag” for the immune system.

• NK Cell Recruitment: Natural Killer (NK) cells recognize the “tail” of the nisevokitug antibody and are drawn to the tumor cell, where they release toxins to destroy it directly—a process known as Antibody-Dependent Cellular Cytotoxicity.

FDA-Approved Clinical Indications

There are currently no FDA-approved indications for nisevokitug.

Clinical research through 2026 has primarily focused on the following CCK2R-high populations:

• Medullary Thyroid Cancer (MTC): Often characterized by massive overexpression of the gastrin receptor.
• Small Cell Lung Cancer (SCLC): Some subtypes of SCLC utilize CCK2R to drive their rapid growth.
• Advanced Gastric (Stomach) Cancer: Particularly in tumors that have become resistant to standard HER2 or PD-1 therapies.
• Neuroendocrine Tumors (NETs): Evaluated for its ability to stabilize disease in slow-growing but persistent endocrine tumors.

Dosage and Administration Protocols

As an investigational drug, nisevokitug dosing is strictly managed within clinical trials (such as the JNJ-77365868-101 study).

Clinical Efficacy and Research Results

As of early 2026, results from Phase 1 and early Phase 2 trials have provided significant biological proof-of-concept:

• Biomarker Evidence: Clinical data has confirmed that nisevokitug successfully reduces the binding of radiolabeled gastrin in treated patients, proving the drug is physically “covering” the intended receptors.
• Disease Stability: In early trials for Medullary Thyroid Cancer, several patients experienced prolonged “stable disease” (no growth) for over 12 months, which is a significant achievement in advanced disease.
• Safety in Combination: Research in 2025 explored combining nisevokitug with checkpoint inhibitors, showing that blocking CCK2R might make the tumor microenvironment more “hospitable” for T-cells to attack.

Safety Profile and Side Effects

The safety profile of nisevokitug is generally considered to be favorable, as CCK2R expression is limited in most healthy tissues.

Common Side Effects (>20%):

• Infusion-Related Reactions: Mild fever, chills, or headache shortly after the infusion.
• Fatigue: General systemic tiredness, manageable with rest.
• Nausea: Usually mild and well-controlled with standard medications.
• Rash: Minor skin redness or itching in some patients.

Serious Risks:

• Neurological Changes: Since CCK2R is present in certain parts of the brain, researchers monitor for rare neurological side effects like anxiety or changes in appetite.
• Gastrointestinal Effects: Potential for changes in stomach acid secretion, though this has been manageable in clinical trials.
• Hematologic Changes: Rare reports of mild drops in white blood cell counts.

Research Areas

In the fields of Stem Cell and Regenerative Medicine, nisevokitug is being used to study “Hormonal Regulation of Stem Cell Niches.” Researchers are investigating how CCK2R signaling influences the “stemness” of gastric cells and whether nisevokitug can be used to prevent the formation of Cancer Stem Cells (CSCs) in the stomach. In 2026, there is also intense focus on “Theranostics.” Scientists are using radiolabeled versions of the nisevokitug antibody to both “see” (image) and “treat” CCK2R-positive tumors simultaneously. Furthermore, studies are exploring its use in combination with proton pump inhibitors (PPIs) to see if altering the hormonal environment of the stomach can make the drug even more effective.

Patient Management and Practical Recommendations

Pre-treatment Requirements:

• CCK2R Biomarker Testing: Most trials require a biopsy or a specialized scan (like a gastrin-receptor scintigraphy) to confirm that the tumor expresses the target.
• Baseline Blood Work: Comprehensive CBC and metabolic panel.

“Do’s and Don’ts” List:

• DO report any “flushing” or shortness of breath immediately during the infusion; these are early signs of an infusion reaction that the nursing team can easily manage.
• DO keep a diary of any changes in your appetite or mood, as CCK2R can have subtle effects on the central nervous system.
• DON’T ignore persistent stomach pain or “rebound” acid reflux, as the drug can alter the way your stomach handles digestion.
• DON’T take high-dose herbal supplements without consulting your oncologist, as they may interfere with the metabolic enzymes that process the antibody.

Legal Disclaimer

The information provided is for educational and informational purposes only and does not constitute medical advice. Nisevokitug (JNJ-77365868) is an investigational agent and is not approved by the U.S. FDA for any indication. Access is limited exclusively to registered clinical trials. Always consult with a qualified oncologist regarding your specific diagnosis and eligibility for research participation.