Pembrolizumab +/− Anetumab Ravtansine for Mesothelioma

Not currently recruiting at 37 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, pembrolizumab and anetumab ravtansine, to evaluate their effectiveness against mesothelioma, a cancer affecting the lung lining. Pembrolizumab (KEYTRUDA) boosts the immune system to fight cancer, while anetumab ravtansine targets cancer cells to deliver chemotherapy directly. The trial seeks to determine if combining these treatments better prevents cancer growth and spread. Individuals with mesothelioma and mesothelin-positive tumors who have already undergone platinum-based chemotherapy may qualify for this study. As a Phase 1, Phase 2 trial, this research aims to understand the treatment's function in people and assess its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using anetumab ravtansine with pembrolizumab is safe for patients. Studies found no major safety problems with these treatments. Anetumab ravtansine is a targeted therapy that attaches to cancer cells and delivers a chemotherapy drug to destroy them. Pembrolizumab is an immunotherapy that helps the immune system fight cancer cells.

In trials, patients generally tolerated this combination therapy well, experiencing no severe side effects. No major safety differences emerged when these treatments were used together, suggesting that both can be safely combined for patient use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they bring new possibilities to the table for mesothelioma, a cancer known for its tough prognosis. Unlike traditional chemotherapy, which attacks cancer cells indiscriminately, anetumab ravtansine is an antibody-drug conjugate that targets mesothelin, a protein often overexpressed in mesothelioma cells, delivering a potent drug directly to the cancer. Pembrolizumab, on the other hand, is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. This combination of targeted delivery and immune system activation offers a novel approach that could potentially improve outcomes for patients with mesothelioma.

What evidence suggests that this trial's treatments could be effective for mesothelioma?

This trial tests two treatment approaches for mesothelioma. One group receives pembrolizumab alone, known to help the immune system fight cancer. Another group receives a combination of anetumab ravtansine and pembrolizumab. Studies have shown that combining anetumab ravtansine with pembrolizumab did not improve response rates compared to pembrolizumab alone. No significant difference was observed in how long patients lived without their cancer worsening between the two groups. The combination treatment was safe but did not show additional benefits. This trial aims to determine if adding anetumab ravtansine, which specifically targets cancer cells, might enhance the effects of pembrolizumab, although current research has not confirmed this yet. ^{1 2 3 4 5}

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.

I am allergic to medications similar to anetumab ravtansine or pembrolizumab.

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

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11416719/

Randomized Trial of Anetumab Ravtansine and ... In that context, the combination of anetumab ravtansine and pembrolizumab did not demonstrate an improvement in confirmed response rates compared to ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0169500224004628

Randomized trial of anetumab ravtansine and ... There were no significant differences in response rates or progression free survival between the combination of anetumab ravtansine and pembrolizumab and ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03126630

NCT03126630 | Pembrolizumab With or Without Anetumab ... Giving pembrolizumab and anetumab ravtansine may work better in treating patients with mesothelin-positive pleural mesothelioma.

4. lungcancerjournal.info lungcancerjournal.info/article/S0169-5002(24)00462-8/abstract

Randomized trial of anetumab ravtansine and pembrolizumab ... The combination of anetumab ravtansine and pembrolizumab were considered safe. · There were no significant differences in response rates or ...

5. jto.org jto.org/article/S1556-0864(23)00831-6/fulltext

OA02.04 Phase 1/2 Randomized Trial of Anetumab ... In phase 2, there was no difference in the confirmed response rates between the combination group (2 PRs, 11%)(p=0.28 by Chi-Square) and the pembrolizumab group ...