Anetumab Ravtansine Clinical Trials

Anetumab ravtansine clinical trials are currently testing the effectiveness and the safety of this experimental drug made by Bayer.[1] Anetumab revtansine selectively targets certain types of cancer cells to deliver a cytotoxic drug directly to them, minimizing harm to healthy cells. These trials provide later-stage patients with another option for treatment.

FREE Mesothelioma Packet

What Are Anetumab Ravtansine and ADCs?

Anetumab ravtansine is an experimental targeted therapy made by German pharmaceutical company Bayer and biotech companies ImmunoGen and MorphoSys. As a targeted treatment, the goal of the medication is to seek out the specific cancer cells and deliver a toxic payload directly into the cancer cells while leaving normal cells relatively unharmed. The title of this particular medication’s mechanism is an antibody-drug conjugate (ADC).[2]

An ADC is a drug that combines an antibody with a cytotoxic drug. An antibody is a protein that recognizes chemical signals on the targeted cells and binds to the abnormal cells preferentially over the normal cells. Researchers have developed antibodies to target cancer cells.[3]

How Does Anetumab Ravtansine Work?

ADCs use the antibody to find and recognize cancer cells and deliver the cytotoxic drug to them. In chemotherapy, patients are given systemic non-specific drugs that are cytotoxic.

This means they circulate the body and kill any fast-growing cells, including both cancer and healthy cells. The delivery system of ADCs like anetumab ravtansine ensures that the drug only goes to and acts upon cancer cells.

The drug is made up of three parts:[3]

• The antibody
• The cytotoxic drug
• A linker molecule that holds them together

When given to the patient, the drug goes through a three-part process:

1. The antibody recognizes and attaches to a specific protein, known as an antigen, present on the surface of the cancer cells.
2. The cancer cell absorbs the entire three-part drug.
3. In the cell, the linker dissolves, and the cytotoxic drug is free to take action and kill the cell.

This ADC (anetumab) has been linked (conjugated) to a highly toxic cytotoxic drug, in this case, called DM4 (ravtansine). Anetumab finds mesothelin and brings the toxic payload directly to cancer cells, where the toxin is delivered into the cell and destroys it. The targeted nature of ADCs means that, if effective, they should produce fewer side effects than traditional therapy.[4]

Does Anetumab Ravtansine Work with Mesothelioma?

For an ADC to work, it must have an antibody that targets an antigen on the surface of cancer cells. Researchers created anetumab ravtansine to target an antigen known as mesothelin.[2]

Mesothelin is not only prevalent on the surface of many mesothelioma cancer cells, but it is also found on the cells that make up many pancreatic and ovarian tumors. Healthy cells may have some mesothelin, but not nearly as much as these cancer cells, so they are not targeted to any significant degree by the drug.[5]

Once anetumab ravtansine is absorbed into a mesothelioma, pancreatic, or ovarian cancer cell, the cytotoxic drug disrupts its ability to thrive. The cell is unable to grow, develop, and divide. This disruption stops cells from dividing, and they simply die.

Clinical Trials with Anetumab Ravtansine

Anetumab ravtansine is a drug giving hope for more treatment options to patients with mesothelioma; however, it is still in clinical trials and is not yet approved.

There are currently two trials associated with the National Institutes of Health and the National Cancer Institute using this drug to treat mesothelioma. We are awaiting results from both of these trials that have recently ended enrollment.

One study that is currently active is evaluating the safety and potential side effects of anetumab ravtansine both in combination with and without another immunotherapy drug called pembrolizumab (Keytruda). Patients involved in this phase I and II trial have pleural mesothelioma and have already undergone chemotherapy.[6]

Another clinical trial that began in 2015 involved patients with advanced pleural mesothelioma or non-small lung cell cancer. Still in phase I, this study looks at the safety and effectiveness of combining anetumab ravtansine with the standard chemotherapy drugs pemetrexed and cisplatin.[7]

In 2020, researchers reported promising results of a study using anetumab ravtansine to target mesothelin-expressing tumors. Participants included 148 people with mesothelioma, ovarian cancer, and other cancers. The researchers intend to press on with more clinical studies based on these new findings.[8]

A Disappointing Failure

Bayer’s early trial of anetumab ravtansine has already failed to meet its target with mesothelioma patients. Participants were either given the trial drug, anetumab ravtansine, or the chemotherapy drug vinorelbine. The study results have so far been disappointing, with no evidence that the drug was any more effective than chemotherapy in the participants.[9]

While the results have been disappointing for this trial, researchers have not given up on anetumab ravtansine. It is a setback but not the end of anetumab ravtansine. The trials that are ongoing or about to start will continue, and there is hope that the results of these trials, including combinations of drugs, will be better.

If you are interested in clinical trials or think you may qualify for a trial with anetumab ravtansine, talk to your oncologist or other members of your medical team. You must meet requirements, and it is also important to consider the risks of joining clinical trials. Immunotherapy drugs like anetumab ravtansine are showing great promise as a new line of treatment for difficult cancers, and patients can help make them better by participating.

Page Medically Reviewed and Edited by Kyle J. Becker, PharmD, MBA, BCOP

Kyle J. Becker, PharmD is certified by the Board of Pharmacy Specialties in Oncology Pharmacy. Dr. Becker earned his pharmacy degree from Shenandoah University and he currently serves as an oncology pharmacist at Parkview Cancer Institute.

Connect with Oncology Pharmacist Kyle J. Becker