cFMS tyrosine kinase inhibitor ARRY-382

Drug Overview

ARRY-382 is a highly specialized, investigational medication used in cancer research. It is a Targeted Therapy that also functions as an Immunotherapy by altering how the body’s immune system interacts with cancer cells.

Here are the key details about this medication:

• Generic Name: cFMS tyrosine kinase inhibitor ARRY-382 (also known as PF-07265804).
• US Brand Names: None. It is currently an investigational drug and does not have a commercial brand name.
• Drug Class: cFMS Tyrosine Kinase Inhibitor / CSF-1R Inhibitor.
• Route of Administration: Oral (taken by mouth as a pill).
• FDA Approval Status: Currently investigational. It is not approved by the US Food and Drug Administration (FDA) for general public use. It is only available to patients participating in specific clinical trials.

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

To understand how ARRY-382 works, it is helpful to look at the environment surrounding a tumor. Tumors often surround themselves with certain immune cells called tumor-associated macrophages (TAMs). Instead of fighting the cancer, these specific macrophages are “tricked” by the tumor into protecting it from the body’s natural defenses.

As a Targeted Therapy, ARRY-382 is designed to seek out and block a specific protein receptor on the surface of these macrophages called the colony-stimulating factor-1 receptor (CSF-1R or cFMS).

Here is how the drug works at the molecular level:

1. Blocking the Signal: The CSF-1R receptor normally receives signals that tell the protecting macrophages to survive and multiply. ARRY-382 binds to this receptor and blocks the signaling pathway.
2. Depleting Tumor Protectors: By cutting off this survival signal, ARRY-382 reduces the number of these tumor-protecting macrophages in the tumor microenvironment.
3. Boosting the Immune Response: With fewer protective macrophages in the way, the body’s actual cancer-fighting immune cells (like T-cells) can better recognize and attack the tumor cells. Because of this, ARRY-382 is often tested in combination with other immunotherapy drugs (like pembrolizumab) to maximize the immune system’s cancer-killing power.

FDA Approved Clinical Indications

Because ARRY-382 is an investigational drug, it does not currently have official FDA-approved indications for routine clinical practice. However, it has been evaluated in clinical trials for the following purposes:

• Oncological Uses (In Clinical Trials):
  • Pancreatic Ductal Adenocarcinoma (PDA): Tested in advanced stages to see if it can shrink tumors when combined with other immunotherapies.
  • Advanced Solid Tumors: Used in patients whose cancers did not respond to standard PD-1/PD-L1 immunotherapy drugs.
  • Platinum-Resistant Ovarian Cancer: Evaluated in ovarian cancer that has stopped responding to traditional platinum-based chemotherapy.
• Non-oncological Uses:
  • There are currently no standard non-oncological uses for this specific medication.

Dosage and Administration Protocols

Because ARRY-382 is still in the research phase, dosages are strictly controlled by clinical trial guidelines. Based on recent Phase 1 and Phase 2 studies, the standard administration is as follows:

Dose Adjustments:

In clinical trials, dose adjustments or temporary pauses are handled on a case-by-case basis by the treating oncologist. Because the drug can elevate liver enzymes, patients with hepatic (liver) stress may require a reduced dose or temporary suspension of the medication until liver function returns to a safe baseline. Standard adjustments for severe renal (kidney) insufficiency are not widely established outside of specific trial protocols.

Clinical Efficacy and Research Results

Recent clinical study data (published between 2020 and 2025) provides insight into how well ARRY-382 works. A major Phase 1b/2 clinical trial (NCT02880371) evaluated ARRY-382 in combination with the immunotherapy drug pembrolizumab in patients with advanced solid tumors.

• Early Phase Success: In the Phase 1b portion of the trial (which included 19 patients), 2 patients (10.5%) experienced a confirmed partial response, meaning their tumors measurably shrank. This included one patient with pancreatic cancer whose tumor shrank for 29.2 months, and one with ovarian cancer lasting 3.1 months.
• Phase 2 Outcomes: In the larger Phase 2 portion, 27 patients with pancreatic cancer were treated. Only 1 patient (3.7%) saw their cancer get better, with the response lasting 2.4 months. Furthermore, no tumor shrinkage was observed in the 19 patients with immunotherapy-resistant solid tumors or the 11 patients with platinum-resistant ovarian cancer.
• Overall Conclusion: The study demonstrated that while the drug successfully reached its target in the body, the overall clinical benefit was limited. Because too few patients saw their cancer improve, researchers chose to stop the study early rather than move forward with broader testing.

Safety Profile and Side Effects

While ARRY-382 avoids many of the traditional side effects of chemotherapy, it still impacts the body’s chemistry.

Black Box Warning: There is no FDA Black Box Warning for this investigational agent.

Common Side Effects (>10%)

• Fatigue: Mild to moderate tiredness was reported in over 50% of patients.
• Elevated Liver Enzymes: Increases in AST and ALT (liver enzymes found in blood tests) were very common, affecting 33% to over 50% of patients, depending on the dose.
• Elevated Muscle Enzymes: Increases in creatine phosphokinase (CPK), an enzyme found in the muscles, occurred in up to 47% of patients.
• Gastrointestinal Issues: Nausea (up to 48%), vomiting, diarrhea, and abdominal pain.
• Anemia: Low red blood cell counts resulting in pale skin or weakness.
• Decreased Appetite: A general loss of desire to eat.

Serious Adverse Events

• Severe Anemia: Requiring medical intervention.
• Pneumonitis: Inflammation of the lung tissue that can cause severe breathing difficulties.
• Fever: High body temperatures requiring medical evaluation to rule out infection.

Management Strategies:

If elevated liver or muscle enzymes are detected during routine blood tests, the medical team will likely lower the dose of ARRY-382 or pause the medication to allow the body to recover. If a patient experiences severe lung inflammation (pneumonitis), the drug is usually stopped permanently, and steroids may be given to reduce the swelling in the lungs.

Connection to Stem Cell and Regenerative Medicine

The target of ARRY-382, the CSF-1 receptor, plays a critical role in the lifecycle of macrophages. Because macrophages originally develop from hematopoietic (blood-forming) stem cells in the bone marrow, drugs that manipulate this pathway are of high interest in regenerative medicine. Researchers are actively studying how altering macrophage behavior can help reshape not just the tumor microenvironment, but also tissue healing, inflammation control, and the success of stem cell transplants. While ARRY-382 is primarily an oncology drug, its mechanism provides valuable data for the broader field of immune-cell reprogramming.

Patient Management and Practical Recommendations

Patients participating in clinical trials for ARRY-382 are monitored closely to ensure maximum safety.

Pre-treatment Tests to be Performed

• Comprehensive Blood Panels: Baseline tests to check liver enzymes (AST/ALT), muscle enzymes (CPK), and complete blood counts (to check for anemia).
• Pregnancy Test: A negative pregnancy test is strictly required for women of childbearing age, as the drug’s effect on an unborn baby is unknown and potentially harmful.
• Baseline Imaging: CT or MRI scans to precisely measure the size of the tumors before starting the medication.

Precautions During Treatment

• Patients must attend all scheduled blood draws, as liver and muscle enzyme spikes often happen without any physical symptoms.
• Patients should report any new or worsening shortness of breath immediately, as this could be a sign of lung inflammation.

“Do’s and Don’ts” List

• DO take the pill at the same time every day to keep a steady amount of the drug in your system.
• DO stay well-hydrated to help your body process the medication.
• DO tell your doctor about all other medications and supplements you take, as they might interact with the study drug.
• DON’T stop taking the medication without consulting your trial doctor, even if you feel unwell.
• DON’T engage in unusually heavy or extreme exercise if your muscle enzymes (CPK) are elevated, as this can cause further muscle stress.

Legal Disclaimer

The information provided in this guide is for educational and informational purposes only and does not constitute medical advice. ARRY-382 is an investigational agent and is not approved by the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA) for general clinical use. It is available only through participation in approved clinical trials. Always consult with a qualified healthcare professional or your treating oncologist regarding diagnosis, treatment options, and eligibility for clinical trials.