M7824 in People With Recurrent Respiratory Papillomatosis

Phase 2

Completed

Conditions: Human Papilloma Virus
Recurrent Respiratory Papillomatosis
Respiratory Papillomatosis
Laryngeal Papilloma, Recurrent

Interventions: Drug: M7824

Registration Number: NCT03707587

Lead Sponsor: National Cancer Institute (NCI)

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.

Detailed Description: Background

* 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 transforming growth factor beta (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 Immunoglobulin G1 (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 (Transforming growth factor, beta 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.

Objective

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

Eligibility

* 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.

Design

* 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 expands 21 patients if one or more complete response(s) is/are observed in the initial patients. With amendment D, dated 7/24/2019, cohort 2 will be closed to further enrollment.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 9

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1200 mg intravenous (IV) of M7824	M7824	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).

Primary Outcome Measures

Name	Time	Method
Proportion of Participants With a Complete Response	Response was assessed by flexible endoscopy with or without imaging studies before treatment and 6 and 12 weeks after starting treatment.	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.

Secondary Outcome Measures

Name	Time	Method
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.	Partial response for M7824 in the treatment of patients with RRP was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Partial Response is defined as a decrease in Derkay anatomic score of 30 percent or greater, and a partial tumor response by imaging using RECIST 1.1 criteria.
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.	Adverse Events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is defined as severe or medically significant but not immediately life-threatening. Grade 4 is defined as life-threatening consequences; urgent intervention indicated.
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.	Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.