Pembrolizumab +/− Anetumab Ravtansine for Mesothelioma

Recruiting at 34 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Platinum-based chemotherapy

Must not be taking: Monoclonal antibodies, CYP3A4 inducers

Disqualifiers: Brain metastases, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 21

49 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase I/II trial studies the side effects and how well pembrolizumab with or without anetumab ravtansine works in treating patients with mesothelin-positive pleural mesothelioma. Anetumab ravtansine is a monoclonal antibody, called anetumab, linked to a chemotherapy drug, called ravtansine. Anetumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as mesothelin receptors, and delivers ravtansine to kill them. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving pembrolizumab and anetumab ravtansine may work better in treating patients with mesothelin-positive pleural mesothelioma.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain medications like strong inhibitors or inducers of CYP3A4, some investigational agents, or certain vaccines during the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What safety data exists for Pembrolizumab and Anetumab Ravtansine in humans?

Pembrolizumab has been studied in various cancers, including lung cancer and mesothelioma, and is generally considered safe, though it can cause immune-related side effects like inflammation in different parts of the body. Anetumab Ravtansine has been tested in mesothelioma patients, but specific safety details are less clear from the available data. ^{1 2 3 4 5}

How is the drug combination of Pembrolizumab and Anetumab Ravtansine unique for treating mesothelioma?

This drug combination is unique because it combines Pembrolizumab, an immunotherapy that helps the immune system attack cancer cells, with Anetumab Ravtansine, an antibody-drug conjugate that targets mesothelin, a protein often found in mesothelioma. This approach aims to enhance the body's immune response while directly delivering a toxic agent to cancer cells, offering a novel strategy for a condition with limited treatment options. ^{1 3 4 6 7}

What data supports the effectiveness of the drug combination Pembrolizumab and Anetumab Ravtansine for treating mesothelioma?

Research shows that Pembrolizumab has shown safety and some effectiveness in treating malignant pleural mesothelioma, while Anetumab Ravtansine has demonstrated anti-tumor activity in mesothelin-expressing cancers, including mesothelioma and ovarian cancer. These findings suggest potential benefits of combining these drugs for mesothelioma treatment. ^{1 3 5 6 8}

Who Is on the Research Team?

Aaron S Mansfield

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for patients with mesothelin-positive pleural mesothelioma who've had platinum-based chemotherapy. They must have measurable disease, normal organ function, and agree to contraception. Exclusions include HIV, hepatitis B/C, recent monoclonal antibody therapy or transfusions, active secondary cancers, certain drug interactions, and history of severe lung conditions.

Inclusion Criteria

My tumor shows high levels of mesothelin in more than 30% of its cells.

You have a low white blood cell count.

Your total bilirubin levels are within the normal range for the hospital where you are being treated.

Exclusion Criteria

I am not taking any strong medication that affects liver enzymes.

I haven't had monoclonal antibody therapy in the last 4 weeks.

You are currently taking any other experimental medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Safety Run-In

Determine the dose of anetumab ravtansine that is safe in combination with pembrolizumab

Up to 2 years

Regular visits as per protocol

Phase II Treatment

Randomized treatment with pembrolizumab alone or in combination with anetumab ravtansine

Up to 24 months

Cycles every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Anetumab Ravtansine
• Pembrolizumab

Trial Overview The study tests pembrolizumab (an immunotherapy) alone or combined with anetumab ravtansine (a targeted therapy that delivers chemo directly to cancer cells). It aims to see if this combination is more effective in treating pleural mesothelioma than pembrolizumab alone.

How Is the Trial Designed?

Group I: Group II (anetumab ravtansine, pembrolizumab) Experimental Treatment 4 Interventions

Patients receive anetumab ravtansine IV over 1 hour and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 12 months for anetumab ravtansine and up to 24 months for pembrolizumab in the absence of disease progression or unacceptable toxicity.

Group II: Group I (pembrolizumab) Active Control 3 Interventions

Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Upon radiologic documentation of disease progression, patients may cross over to Group II.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study involving 25 patients with PD-L1-positive malignant pleural mesothelioma, pembrolizumab demonstrated a 20% objective response rate, indicating potential anti-tumor activity in this aggressive cancer.

The treatment was generally well tolerated, with 64% of patients experiencing treatment-related adverse events, but no treatment-related deaths occurred, suggesting a favorable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. Alley, EW., Lopez, J., Santoro, A., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, an anti-PD-1 antibody used for treating malignant pleural mesothelioma, can cause serious side effects such as minimal change disease (MCD), which was identified in a 62-year-old patient who developed nephrotic syndrome and acute renal failure after treatment.

The patient's symptoms improved significantly after discontinuing pembrolizumab and starting steroid treatment, highlighting the importance of monitoring renal function and recognizing potential autoimmune reactions in patients receiving this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-associated minimal change disease in a patient with malignant pleural mesothelioma. Bickel, A., Koneth, I., Enzler-Tschudy, A., et al.[2022]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Anetumab ravtansine versus vinorelbine in patients with relapsed, mesothelin-positive malignant pleural mesothelioma (ARCS-M): a randomised, open-label phase 2 trial. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Safety and activity of anti-mesothelin antibody-drug conjugate anetumab ravtansine in combination with pegylated-liposomal doxorubicin in platinum-resistant ovarian cancer: multicenter, phase Ib dose escalation and expansion study. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Clinical Trials Eligibility of Patients With Malignant Pleural Mesothelioma: Use of Novel Therapies and Outcomes. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

First-in-Human, Multicenter, Phase I Dose-Escalation and Expansion Study of Anti-Mesothelin Antibody-Drug Conjugate Anetumab Ravtansine in Advanced or Metastatic Solid Tumors. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

7. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab-associated minimal change disease in a patient with malignant pleural mesothelioma. [2022]