History of Changes for Study: NCT03707587
M7824 in People With Recurrent Respiratory Papillomatosis
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Study Record Versions
Version A B Submitted Date Changes
1 October 13, 2018 None (earliest Version on record)
2 October 16, 2018 Study Status
3 October 17, 2018 Study Status
4 October 18, 2018 Study Status
5 October 19, 2018 Study Status
6 October 20, 2018 Study Status
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14 November 1, 2018 Study Status
15 November 2, 2018 Study Status
16 November 3, 2018 Study Status
17 November 6, 2018 Recruitment Status, Study Status, References and Contacts/Locations
18 November 7, 2018 Study Status
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44 December 15, 2018 Study Status
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47 December 20, 2018 Study Status
48 December 21, 2018 Study Status
49 February 21, 2019 Eligibility and Study Status
50 February 27, 2019 Study Status
51 March 18, 2019 Recruitment Status, Study Status, Contacts/Locations and References
52 May 24, 2019 Study Status
53 May 25, 2019 Recruitment Status, Study Status, Contacts/Locations, References and Eligibility
54 May 30, 2019 Study Status
55 September 19, 2019 Eligibility and Study Status
56 September 21, 2019 Eligibility, Study Design, Study Description and Study Status
57 September 24, 2019 Study Status
58 October 2, 2019 Recruitment Status, Study Status, Contacts/Locations, Study Design and References
59 October 18, 2019 Study Status
60 January 9, 2020 Study Status
61 April 17, 2020 Study Status
62 June 20, 2020 Study Status
63 July 11, 2020 Study Status
64 August 13, 2020
Quality Control Review has not concluded Returned: August 28, 2020
Outcome Measures, Arms and Interventions, Sponsor/Collaborators, Study Status, Study Description, Document Section, IPDSharing, Eligibility, Study Design and Oversight
65 September 1, 2020
Quality Control Review has not concluded Returned: September 21, 2020
Outcome Measures, Study Status, Adverse Events and Baseline Characteristics
66 September 22, 2020 Study Status, Baseline Characteristics
67 September 23, 2021 Document Section, More Information, Study Status, Contacts/Locations and Sponsor/Collaborators
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Study NCT03707587
Submitted Date:  October 13, 2018 (v1)

Open or close this module Study Identification
Unique Protocol ID: 190002
Brief Title: M7824 in People With Recurrent Respiratory Papillomatosis
Official Title: A Phase II Study of M7824 in Subjects With Recurrent Respiratory Papillomatosis
Secondary IDs: 19-C-0002
Open or close this module Study Status
Record Verification: October 9, 2018
Overall Status: Not yet recruiting
Study Start: October 19, 2018
Primary Completion: July 7, 2020 [Anticipated]
Study Completion: July 6, 2022 [Anticipated]
First Submitted: October 12, 2018
First Submitted that
Met QC Criteria:
October 13, 2018
First Posted: October 16, 2018 [Actual]
Last Update Submitted that
Met QC Criteria:
October 13, 2018
Last Update Posted: October 16, 2018 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: National Cancer Institute (NCI)
Responsible Party: Sponsor
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring:
Open or close this module Study Description
Brief Summary:


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.


To see if M7824 works in treating recurrent respiratory papillomatosis.


Adults ages 18 years or older with recurrent respiratory papillomatosis


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....

Detailed Description:


  • Recurrent respiratory papillomatosis (RRP) is a rare papillomatous disease of the aerodigestive tract that is caused by the Human Papilloma Virus (HPV).
  • RRP can progress to cause airway compromise, fatal pulmonary lesions, and invasive cancers.
  • There is no effective systemic therapy for RRP. Patients typically require repeated interventional procedures for disease control.
  • A recently completed phase II clinical trial investigating avelumab in subjects with aggressive RRP demonstrated an acceptable safety profile from Avelumab and a high rate of partial responses.
  • RRP is characterized by frequent expression of PD-L1 and TGF-beta in the tumor microenvironment.
  • This clinical trial will evaluate the activity of M7824, a novel bifunctional fusion protein composed of a fully human IgG1 monoclonal antibody against human PD-L1 (avelumab) fused, via a flexible glycine-serine linker, to the soluble extracellular domain of human TGF- B receptor II (TGF-BRII), which functions as a TGF-B trap. This drug was selected for its demonstrated activity in a variety of cancers and for its acceptable safety profile.


- Determine the complete response rate for M7824 in the treatment of patients with RRP.


  • Histologically confirmed diagnosis of RRP.
  • 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.
    • Tracheal involvement with RRP that has required either two or more endoscopic interventions in the last 12 months or a tracheostomy.
  • Age 18 years or greater.
  • Eastern Oncology Cooperative Group Performance Score of 0 or 1.


  • This is a phase II clinical trial with two cohorts that will enroll simultaneously.
  • Cohort 1 will consist of subjects who have not been treated previously with an immune checkpoint inhibitor. Cohort 2 will consist of subjects whose disease has been treated previously with andrefractory to an immune checkpoint inhibitor. Each cohort will have a Simon optimal two-stage design with initial enrollment of 12 patients and expans 21 patients if one or more complete response(s) is/are observed in the initial patients.
Open or close this module Conditions
Conditions: Recurrent Respiratory Papillomatosis
Respiratory Papillomatosis
Laryngeal Papilloma, Recurrent
Human Papilloma Virus
Keywords: Human Papilloma Virus (HPV)
Monoclonal Antibody
PD-L1 Expression
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 45 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Arm 1
Patients will receive 1200 mg 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
Patients will receive 1200 mg IV of M7824 on day 1 of a 14 day cycle, every other week, for up to 12 weeks total treatment (6 cycles).
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Complete Response Rate
[ Time Frame: every 6 weeks x 3, then every 12 weeks x 3, then every 26 weeks x 2 or until disease progression ]

To determine the complete response rate for M7824 in the treatment of patients with RRP.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 99 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No

RRP criteria:

  • Histological diagnosis of RRP confirmed by pathology report from a 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 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 ECOG 0 or1.
  • 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:
    • WBC > 2000/ microliter
    • Neutrophils > 1000/ microliter
    • Platelets > 75 x10(3)/ microliter
    • Hemoglobin > 9.0 g/dL
    • Serum Creatinine < 1.5 x ULN OR eGFR > 30 mL/min (measured or calculated using the MDRD equation).
    • AST/ALT :S 2.5 x ULN; for subjects with documented metastatic disease to the liver, AST and ALT levels :S 5 x ULN
    • Total Bilirubin :S 1.5 x ULN
  • Sexually active subjects (men and women) of reproductive potential must agree to use two methods of contraception: one highly effective and one other effective method for at least 28 days prior, throughout the M7824 treatment and for at least 60 days after M7824 treatment. Highly Effective Methods are defined as: Intrauterine device (IUD), hormonal (birth control pills, injections, implants), tubal ligation and partner s vasectomy; Other are defined as: latex condom, diaphragm and cervical cap.
  • Seronegative for HIV antibody. The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune function and thus are likely less responsive to the experimental treatment.
  • Seronegative for hepatitis B antigen, positive hepatitis B tests can be further evaluated by confirmatory tests (Hep B DNA Quant, HBV Viral Load), and if confirmatory tests are negative, the patient can be enrolled.
  • Seronegative for hepatitis C antibody unless antigen negative. If hepatitis C antibody test is positive, then patients must be tested for the presence of antigen by Hep C RNA Quant, HCV Viral Load and be HCV RNA negative.


  • Any severe acute or chronic medical or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior, liver disease, lung disease (with the exception of what is specified in inclusion criteria) , or laboratory abnormalities that, in the opinion of the investigators, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results and in the judgment of the investigator, would make the patient inappropriate for entry into this study. Patients with mild to moderate asthma or chronic obstructive pulmonary disease (COPD) well controlled with oral or inhaled medications are permitted to enroll.
  • 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 NCI-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), unstab1e angina, congestive heart fai1ure (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 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 or 4 weeks after the last dose of M7824 are prohibited.
Open or close this module Contacts/Locations
Central Contact Person: Erin W Ferraro, R.N.
Telephone: (833) 815-0387
Study Officials: Christian S Hinrichs, M.D.
Principal Investigator
National Cancer Institute (NCI)
Locations: United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Contact:Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links: Description: NIH Clinical Center Detailed Web Page
Available IPD/Information:

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