OT-101 + Pembrolizumab for Mesothelioma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Oncotelic Inc.

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Pregnancy, Active infection, Autoimmune, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: Approximately 24 months

63 Participants Needed

Trial Summary

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 have received certain treatments like systemic anti-cancer therapy or radiotherapy shortly before starting the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug OT-101 + Pembrolizumab for treating mesothelioma?

Research shows that pembrolizumab, one of the drugs in the treatment, has shown promise in treating mesothelioma, a type of cancer, by helping the immune system fight the cancer cells. Studies have reported positive outcomes in patients with mesothelioma who were treated with pembrolizumab, suggesting it may be effective in this combination therapy. ^{1 2 3 4 5}

Is the combination of OT-101 and pembrolizumab safe for humans?

The safety of pembrolizumab has been evaluated in several studies for mesothelioma, showing it is generally safe for use in humans, but there is no specific safety data available for the combination of OT-101 and pembrolizumab. ^{1 2 3 4 6}

What makes the drug OT-101 + Pembrolizumab unique for treating mesothelioma?

OT-101 (Trabedersen) combined with pembrolizumab is unique because it targets specific pathways involved in cancer growth and immune response, potentially offering a new approach for mesothelioma, which has limited treatment options. Pembrolizumab is an immunotherapy that helps the immune system attack cancer cells, while OT-101 may work by inhibiting certain proteins that promote tumor growth. ^{1 2 3 4 5}

What is the purpose of this trial?

This is a study of OT-101, a TGF-b2 inhibitor in combination of pembrolizumab in patients with malignant pleural mesothelioma. Both efficacy assessment, and safety and tolerability of various dose of OT-101 in combination of pembrolizumab are evaluated.

Eligibility Criteria

This trial is for adults with Malignant Pleural Mesothelioma who didn't respond to previous treatments including anti-PD-1/L1 or anti-CTLA-4 antibodies, possibly with chemotherapy. They must have measurable disease, adequate organ function, and agree to contraception. Excluded are those with a recent second cancer, active autoimmune diseases needing treatment within 2 years, severe allergies to pembrolizumab components, certain infections or immunodeficiencies.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

I am 18 or older with a confirmed diagnosis of Malignant Pleural Mesothelioma.

I can provide a tissue sample from my tumor before starting treatment.

Exclusion Criteria

You have a severe allergic reaction to pembrolizumab or any of the substances it contains.

I have not received a live vaccine in the last 30 days.

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in Dose-Escalation

Evaluation of safety and tolerability of various doses of OT-101 in combination with pembrolizumab to determine the recommended Phase 2 dose (RP2D)

4 days continuous infusion every two weeks

Continuous monitoring during infusion

Treatment

Participants receive OT-101 at RP2D and pembrolizumab for efficacy assessment

Approximately 24 months

Pembrolizumab administered every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Treatment Details

Interventions

• OT-101

Trial Overview The study tests OT-101 combined with pembrolizumab in patients whose mesothelioma has progressed after checkpoint inhibitor therapy. It aims to evaluate the effectiveness and safety of various doses of OT-101 (a TGF-b2 inhibitor) alongside pembrolizumab.

Participant Groups

Group I: Drug OT-101 plus pembrolizumab Experimental Treatment 1 Intervention

OT-101 will be administered at a RP2D dose/m2/day for 4 days continuously and 10 days off every two weeks via a portable infusion pump. Pembrolizumab will be administered with the standard regimen of 400 mg intravenously (IV) every six weeks.

OT-101 is already approved in United States for the following indications:

Approved in United States as OT-101 for:

• None approved yet; under investigation for pancreatic cancer, glioblastoma, melanoma, and other cancers

Who Is Running the Clinical Trial?

Oncotelic Inc.

Lead Sponsor

Trials

3

Recruited

540+

Findings from Research

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 the KEYNOTE-158 study involving 118 patients with previously treated malignant pleural mesothelioma (MPM), pembrolizumab demonstrated an 8% objective response rate, with a median duration of response of 14.3 months, indicating its potential efficacy as a treatment option regardless of PD-L1 status.

The treatment was associated with manageable safety, as 69% of patients experienced treatment-related adverse events, with serious events occurring in 12%, highlighting the need for careful monitoring but suggesting that pembrolizumab can be tolerated in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab in patients with advanced mesothelioma in the open-label, single-arm, phase 2 KEYNOTE-158 study. Yap, TA., Nakagawa, K., Fujimoto, N., et al.[2021]

References

1. 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]

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

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

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

Pembrolizumab as Palliative Immunotherapy in Malignant Pleural Mesothelioma. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab in patients with advanced mesothelioma in the open-label, single-arm, phase 2 KEYNOTE-158 study. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab. [2020]

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

New Immunotherapy Combinations Enter the Battlefield of Malignant Mesothelioma. [2022]