A Study of Pembrolizumab and Radiation Therapy in People With Mesothelioma

NCT04897022 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 21-197
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to find out whether IMPRINT in combination with pembrolizumab is a safe treatment for people with malignant pleural mesothelioma (MPM).The highest dose of IMPRINT that causes few or mild side effects when given in combination with pembrolizumab will be found. Once the highest safe dose of IMPRINT is found, it will be tested in combination with pembrolizumab in future participants to see whether the combination may be an effective treatment for MPM.

Conditions

Malignant Pleural Mesothelioma

Keywords

malignant pleural mesothelioma; MPM; intensity-modulated pleural radiation therapy; IMPRINT; Pembrolizumab; 21-197; Memorial Sloan Kettering Cancer Center

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of IMPRINT

  The first primary objective of this study is to determine the MTD of IMPRINT among the three candidate doses: 400cGy x5 fractions, 500cGy x5 fractions and 600cGy x5 fractions. These dose levels will be evaluated using a modified Continuous Reassessment Method (CRM) starting with the lowest dose level 400cGy x5 fractions. Determined by the first 12 participants enrolled to the study.

  6 months

Study Arms (1)

Participants with malignant pleural mesothelioma (MPM)

EXPERIMENTAL

Participants will be diagnosed with malignant pleural mesothelioma and be deemed unresectable per thoracic surgeon assessment

Drug: Pembrolizumab; Radiation: IMPRINT

Interventions

Pembrolizumab DRUG

Fixed dose of pembrolizumab 200mg IV q3 weeks

Participants with malignant pleural mesothelioma (MPM)

IMPRINT RADIATION

The starting radiation dose will consist of 400cGy x5 fractions. Doses will be escalated by 100cGy per fraction (i.e. 400cGy, 500cGy, 600cGy) for a total of 3 dose levels. The MTD will be evaluated using a modified Continuous Reassessment Method. Dose limiting toxicities (DLTs) are defined as any treatment-related non-hematologic toxicity with a CTCAE v5 Grade ≥3 or grade ≥2 pneumonitis that requires use of steroids occurring after the start of IMPRINT through the first 3 months after the last fraction.

Also known as: intensity-modulated pleural radiation therapy

Participants with malignant pleural mesothelioma (MPM)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically confirmed diagnosis of malignant pleural mesothelioma
• Unresectable per thoracic surgeon assessment
• At least one prior line of systemic therapy. Note: Patients who were on prior immunotherapy are eligible.
• ECOG 0-1
• PFTs: DLCO \>40% predicted, FEV1 \>50% predicted
• Male/female participants who are at least 18 years of age on the day of signing informed consent
• Disease outside the ipsilateral thorax allowed as long as it has either been treated definitively and been stable for 6 months
• Male participants:
• A male participant must agree to use a contraception as detailed in Appendix 1 of this protocol during the treatment period and for at least 30 days, corresponding to time needed to eliminate any study treatment(s) (pembrolizumab and or any active comparator/combination) plus an additional 120 days (a spermatogenesis cycle) for study treatments with evidence of genotoxicity at any dose after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants:
• A female participant is eligible to participate if she is not pregnant (see Appendix 1), not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 1 OR
• A WOCBP who agrees to follow the contraceptive guidance in Appendix 1 during the treatment period and for at least 120 days (corresponding to time needed to eliminate any study treatment(s) (pembrolizumab and or any active comparator/combination) plus 30 days (a menstruation cycle) for study treatments with risk of genotoxicity after the last dose of study treatment.
• The participant (or legally authorized representative if applicable) provides written informed consent for the trial.
• Have a ECOG performance status of 0 to 1. Evaluation of ECOG is to be performed within 30 days prior to the date of allocation.

You may not qualify if:

• Newly diagnosed MPM
• Prior thoracic radiation therapy or intrapleural therapy
• Bulky disease in the fissure preventing IMPRINT
• Serious infection, concurrent active malignancies, or other serious medical illness
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137) within 4 weeks prior to study Day 1 or has not recovered (i.e., ≥ Grade 1 at baseline) from adverse events due to a previously administered agent
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. Low grade malignancies not requiring active treatment are not excluded.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression, clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has a known history of Human Immunodeficiency Virus (HIV).

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited protocol activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Suffolk- Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited protocol activities)

Rockville Centre, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

pembrolizumab; Imprint II

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Charles Simone, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2021
• First Posted: May 21, 2021
• Study Start: August 10, 2021
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (7)