Anetumab ravtansine clinical trials are currently testing the effectiveness and the safety of this experimental cancer and mesothelioma drug made by Bayer. 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.
What Is Anetumab Ravtansine?
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.
Antibody-Drug Conjugate
Anetumab ravtansine is actually a combination of compounds called an antibody-drug conjugate (ADC).[1]
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.[2]
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 cytotoxic drugs.
This means they circulate in 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:[2]
- 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:
- The antibody recognizes and attaches to a specific protein, known as an antigen, present on the surface of the cancer cells.
- The cancer cell absorbs the entire three-part drug.
- 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.[3]
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.[1]
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.[4]
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. It is still in the clinical trial stage and is not yet FDA-approved.
Anetumab Ravtansine and Pancreatic Cancer
Mesothelin pancreatic cancer is one application of anetumab ravtansine currently under study. In fact, the only clinical trial using the ADC and actively recruiting participants is for pancreatic cancer.
The study is called Testing the Combination of Anetumab Ravtansine With Either Nivolumab, Nivolumab and Ipilimumab, or Gemcitabine and Nivolumab in Advanced Pancreatic Cancer.[5]
This is a phase I study determining dosing and side effects of the treatment. Pancreatic cancer, like mesothelioma, often expresses a lot of mesothelin. If anetumab ravtansine proves safe and effective for these patients, it could be useful for mesothelioma patients too.
Ongoing and Completed Mesothelioma Anetumab Ravtansine Clinical Trials
There are currently no anetumab ravtansine trials associated with the National Institutes of Health and the National Cancer Institute recruiting mesothelioma patients. Ongoing and recently completed trials include:
- Pembrolizumab With or Without Anetumab Ravtansine in Treating Patients With Mesothelin-Positive Pleural Mesothelioma. 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]
- Phase Ib Study of Anetumab Ravtansine in Combination With Pemetrexed and Cisplatin in Mesothelin-expressing Solid Tumors. Another clinical trial that began in 2015 involved patients with advanced pleural mesothelioma or non-small lung cell cancer. Complete and awaiting results, this study looked at the safety and effectiveness of combining anetumab ravtansine with the standard chemotherapy drugs pemetrexed and cisplatin.[7]
- Phase II Anetumab Ravtansine as 2nd Line Treatment for Malignant Pleural Mesothelioma (MPM). This study finished in 2020 and reported results in 2022. The researchers concluded that anetumab was safe for patients but did not provide better results than vinorelbine, the control group treatment.[8]
- In 2020, researchers reported promising phase I study results 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.[9]
A Disappointing Failure for Mesothelioma Patients
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.[10]
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.
