M7824 in People With Recurrent Respiratory Papillomatosis

NCT03707587 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 19000219-C-0002
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Programmed cell death protein 1 (PD-L1) is a protein on the surface of cells. It regulates if a cell can be killed by immune system cells. It is thought to be able to affect the immune system response to diseased cells like those infected with a virus. The molecule M7824 interferes with the activity of PD-L1. It could help the immune system kill cells infected with a virus . Since recurrent respiratory papillomatosis is caused by a virus infection, this molecule could help. Objective: To see if M7824 works in treating recurrent respiratory papillomatosis. Eligibility: Adults ages 18 years or older with recurrent respiratory papillomatosis Design: Participants will be screened with: Medical history Physical exam Blood and pregnancy tests Endoscopy procedure in clinic. A small tube with a camera will look at the inside of the nose, throat, larynx, and upper windpipe. Some participants will also be screened with a chest scan. At the start of the study, participants will: Have a sedated endoscopy procedure where biopsies will be taken. Have blood tests. Have apheresis. Blood will be collected by a tube in an arm vein. A machine will remove white blood cells. The rest of the blood will be returned into an arm vein. Fill out a voice questionnaire. Participants will get the study molecule into a vein over about 1 hour. They will get it every other week for up to 12 weeks. Participants will repeat screening and starting procedures throughout the study. They will also review side effects and any medicine they are taking. When they are done with the study treatment, participants will be evaluated by repeating the study procedures. They may be evaluated periodically until their disease progresses.

Conditions

Recurrent Respiratory Papillomatosis; Respiratory Papillomatosis; Laryngeal Papilloma, Recurrent; Human Papilloma Virus

Keywords

Human Papilloma Virus (HPV); Monoclonal Antibody; PD-L1 Expression

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants With a Complete Response

  Complete response for M7824 in the treatment of patients with RRP was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response is defined as no evidence of papillomas on physical exam and/or clinic-based flexible nasopharyngolaryngoscopy and/or tracheoscopy or by exam under anesthesia (sedation or general anesthesia) with endoscopy and biopsies, and absence of disease by imaging if lesions are assessed by imaging.

  Response was assessed by flexible endoscopy with or without imaging studies before treatment and 6 and 12 weeks after starting treatment.

Secondary Outcomes (3)

• Number of Participants With a Partial Response

  Response was assessed by flexible endoscopy with or without imaging studies before treatment and 6 and 12 weeks after starting treatment.

• Number of Participants With ≥Grade 3 Adverse Events

  Per protocol, adverse events are documented from the first administration of the study therapy, Study Day 1, through 42 days after the study therapy was last administered, up to 24 weeks + 42 days.

• Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  Per protocol, adverse events are documented from the first administration of the study therapy, Study Day 1, through 42 days after the study therapy was last administered, up to 24 weeks + 42 days.

Study Arms (1)

1200 mg intravenous (IV) of M7824

EXPERIMENTAL

Patients will receive 1200 mg intravenous (IV) of M7824 on day 1 of a 14 day cycle, every other week, for up to 12 weeks total treatment (6 cycles).

Drug: M7824

Interventions

M7824 DRUG

Patients will receive 1200 mg intravenous (IV) of M7824 on day 1 of a 14 day cycle, every other week, for up to 12 weeks total treatment (6 cycles).

1200 mg intravenous (IV) of M7824

Eligibility Criteria

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

You may qualify if:

• Recurrent Respiratory Papillomatosis (RRP) criteria:
• Histological diagnosis of RRP confirmed by pathology report from a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
• One of the following:
• A Derkay anatomic score of 10 or greater and a history of two or more endoscopic interventions in the last 12 months for control of RRP.
• Pulmonary RRP with pulmonary disease that is measurable by computed tomography scan and evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria.
• Tracheal involvement with RRP that has required either two or more endoscopic interventions in the last 12 months or a tracheostomy.
• Greater than or equal to 18 years of age.
• Able to understand and sign the Informed Consent Document.
• Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
• Willing to undergo endoscopic evaluation with biopsies in compliance with this protocol.
• No systemic therapy for RRP for at least 3 half-lives of the prior drug(s).
• Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to first dose:
• White Blood Count (WBC) \> 2000/ microliter
• Neutrophils \> 1000/ microliter
• Platelets \> 75 x10(3)/ microliter

You may not qualify if:

• Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, or psoriasis not requiring systemic treatment, are permitted to enroll.
• Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled, topical intranasal or intro-ocular steroids, and adrenal replacement doses \<10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Prior organ transplantation, including allogeneic stem cell transplantation.
• Patients who are receiving any other investigational agents
• Pregnant or breast feeding. Women of childbearing potential must have a negative pregnancy test at screening. Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Post-menopause is defined as amenorrhea greater than or equal to 12 consecutive months. Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti- estrogens, ovarian suppression or any other reversible reason.
• History of allergy to study drug components.
• History of severe hypersensitivity reaction to any monoclonal antibody (Grade greater than or equal to 3 National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v 5.0), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma).
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (greater than or equal to New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
• Persisting toxicity related to prior therapy of Grade \>1 NCI-CTCAE v 5.0; however, alopecia, sensory neuropathy Grade less than or equal to 2 or other Grade less than or equal to 2 adverse events (AEs) not constituting a safety risk based on investigator's judgment are acceptable.
• Known alcohol or drug abuse.
• Vaccination within 4 weeks of the first dose of M7824 and 4 weeks after the last dose of M7824 are prohibited.
• Human papillomavirus (HPV) vaccination within one year of the first dose of M7824
• With amendment D, patients that received prior Programmed cell death protein 1 (PD-1) based immunotherapy will be excluded.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Robbins Y, Friedman J, Clavijo PE, Sievers C, Bai K, Donahue RN, Schlom J, Sinkoe A, Hinrichs CS, Allen C, Abdul Sater H, Gulley JL, Norberg S. Dual PD-L1 and TGF-b blockade in patients with recurrent respiratory papillomatosis. J Immunother Cancer. 2021 Aug;9(8):e003113. doi: 10.1136/jitc-2021-003113.

  PMID: 34462327 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Recurrent respiratory papillomatosis

Results Point of Contact

• Title: Dr. Scott Norberg
• Organization: National Cancer Institute

scott.norberg@nih.gov

301-275-9668

Study Officials

• Scott Norberg, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 12, 2018
• First Posted: October 16, 2018
• Study Start: December 19, 2018
• Primary Completion: October 29, 2019
• Study Completion: July 6, 2022
• Last Updated: September 29, 2022
• Results First Posted: October 14, 2020

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)