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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of two drugs, OT-101 (Trabedersen) and pembrolizumab, to determine their effectiveness and safety for individuals with malignant pleural mesothelioma, a cancer affecting the lung lining. The researchers aim to discover if this combination can control the disease in patients who have not responded to other cancer treatments. Suitable candidates for this trial have malignant pleural mesothelioma and have experienced cancer progression after treatments like anti-PD-1 or anti-CTLA-4 medications. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering hope to those seeking new options.

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.

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

Research shows that pembrolizumab, one of the drugs in this trial, has been well-studied and is generally well-tolerated for treating mesothelioma. Patients with mesothelioma have experienced positive results with pembrolizumab, suggesting it may be a safe part of the combination treatment.

The other drug in this trial, OT-101, has been tested in other conditions, including COVID-19. While researchers continue to study OT-101, human trials have provided some early insights into its safety. However, since this study is in the early stages, the complete safety profile for OT-101 combined with pembrolizumab is still under evaluation.

Current sources do not provide specific information on side effects, so discussing potential risks and benefits with the trial team is important before deciding to join. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about OT-101 for mesothelioma because it introduces a fresh approach that sets it apart from the standard chemotherapy options like pemetrexed and cisplatin. Unlike these traditional treatments, OT-101 is an antisense oligonucleotide therapy designed to block the activity of a specific protein that helps cancer cells grow. This targeted mechanism may offer a more precise attack on cancer cells with potentially fewer side effects. Additionally, when combined with pembrolizumab, an immunotherapy drug that unleashes the body's immune response against cancer, this combo could enhance the overall effectiveness against mesothelioma.

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

Research has shown that pembrolizumab has produced positive results for patients with mesothelioma, suggesting it might work well when combined with OT-101. In this trial, participants will receive a combination of OT-101 and pembrolizumab. OT-101 blocks a protein that can aid cancer growth and is being tested for its effectiveness with pembrolizumab. Early results suggest that these treatments together could improve outcomes for patients with malignant pleural mesothelioma, a cancer affecting the lung lining. Although complete data on this combination is not yet available, the success of pembrolizumab alone offers hope for the combination's effectiveness. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/347781

OT-101 in Combination With Pembrolizumab in Subjects ... This is a study of OT-101, a TGF-b2 inhibitor in combination of pembrolizumab in patients with malignant pleural mesothelioma. Both efficacy assessment ...

2. biospace.com biospace.com/oncotelic-initiates-phase-2-trial-evaluating-ot-101-in-combination-with-keytruda-for-mesothelioma

Oncotelic Initiates Phase 2 Trial Evaluating OT-101 in ... Oncotelic is seeking to leverage its deep expertise in oncology drug development to improve treatment outcomes and survival of cancer patients ...

3. withpower.com withpower.com/trial/phase-2-mesothelioma-11-2022-b20c9

OT-101 + Pembrolizumab for Mesothelioma Studies have reported positive outcomes in patients with mesothelioma who were treated with pembrolizumab, suggesting it may be effective in this combination ...

4. cancernetwork.com cancernetwork.com/view/trabedersen-ot-101-with-pembrolizumab-for-newly-diagnosed-pd-l1-positive-metastatic-nsclc

Trabedersen (OT-101) With Pembrolizumab for Newly ... This is an investigator-initiated phase 1/2 trial (NCT06579196) that evaluates the combination of pembrolizumab and trabedersen in patients with ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06579196

Study Details | NCT06579196 | Trabedersen (OT-101) With ... The goal of this clinical trial is to: 1) evaluate the safety and recommended dose of the drug OT-101/Trabedersen when combined with Pembrolizumab and 2) ...