NCT03707587

M7824 in People With Recurrent Respiratory Papillomatosis

Completed Phase 2 Results posted Last updated 29 September 2022

What this trial tests

Phase 2 trial testing M7824 in Recurrent Respiratory Papillomatosis in 9 participants. Completed in 6 July 2022.

Timeline

19 December 2018

Primary endpoint
29 October 2019

6 July 2022

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	9
Start date	19 December 2018
Primary completion	29 October 2019
Estimated completion	6 July 2022
Sites	1 location across United States

Drugs / interventions tested

• M7824 — full drug profile →

Conditions studied

• Recurrent Respiratory Papillomatosis — all drugs for Recurrent Respiratory Papillomatosis →
• Respiratory Papillomatosis — all drugs for Respiratory Papillomatosis →
• Laryngeal Papilloma, Recurrent — all drugs for Laryngeal Papilloma, Recurrent →
• Human Papilloma Virus — all drugs for Human Papilloma Virus →

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Recurrent Respiratory Papillomatosis or Respiratory Papillomatosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Proportion of Participants With a Complete Response Primary · 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.

Group	Value	95% CI
Cohort 1 - Checkpoint Inhibitor Naive Patients	0
Cohort 2 - Patients Refractory to Checkpoint Inhibition	0

Number of Participants With a Partial Response Secondary · 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.

Group	Value	95% CI
Cohort 1 - Checkpoint Inhibitor Naive Patients	1
Cohort 2 - Patients Refractory to Checkpoint Inhibition	0

Number of Participants With ≥Grade 3 Adverse Events Secondary · 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.

Grade 3 Dyspnea

Group	Value	95% CI
Cohort 1 - Checkpoint Inhibitor Naive Patients	1
Cohort 2 - Patients Refractory to Checkpoint Inhibition	0

Grade 3 Hypertension

Group	Value	95% CI
Cohort 1 - Checkpoint Inhibitor Naive Patients	1
Cohort 2 - Patients Refractory to Checkpoint Inhibition	1

Grade 3 Laryngeal obstruction

Group	Value	95% CI
Cohort 1 - Checkpoint Inhibitor Naive Patients	4
Cohort 2 - Patients Refractory to Checkpoint Inhibition	1

Grade 3 Lung infection

Group	Value	95% CI
Cohort 1 - Checkpoint Inhibitor Naive Patients	1
Cohort 2 - Patients Refractory to Checkpoint Inhibition	0

Grade 3 Pain

Group	Value	95% CI
Cohort 1 - Checkpoint Inhibitor Naive Patients	1
Cohort 2 - Patients Refractory to Checkpoint Inhibition	0

Grade 3 Sore throat

Group	Value	95% CI
Cohort 1 - Checkpoint Inhibitor Naive Patients	1
Cohort 2 - Patients Refractory to Checkpoint Inhibition	1

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

Group	Value	95% CI
Cohort 1 - Checkpoint Inhibitor Naive Patients	7
Cohort 2 - Patients Refractory to Checkpoint Inhibition	2

Adverse events — posted to ClinicalTrials.gov

Time frame: 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. Beyond 42 days after the last administration (end of treatment), only adverse events which are serious and related to the M7824 need to be recorded until the patient is off study.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1 - Checkpoint Inhibitor Naive Patients

Serious: 3/7 (43%)

Deaths: 0/7

Cohort 2 - Patients Refractory to Checkpoint Inhibition

Serious: 2/2 (100%)

Deaths: 1/2

Serious adverse events (3 terms)

Reaction	System	Cohort 1 - Checkpoint Inhi…	Cohort 2 - Patients Refrac…
Laryngeal obstruction	Respiratory, thoracic and mediastinal disorders	—	—
Lung infection	Infections and infestations	—	—
Sudden death NOS	General disorders	—	—

Other adverse events (12 terms — click to expand)

Reaction	System	Cohort 1 - Checkpoint Inhi…	Cohort 2 - Patients Refrac…
Sore throat	Respiratory, thoracic and mediastinal disorders	—	—
Hypertension	Vascular disorders	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—
Diarrhea	Gastrointestinal disorders	—	—
Hypophosphatemia	Metabolism and nutrition disorders	—	—
Laryngeal obstruction	Respiratory, thoracic and mediastinal disorders	—	—
Lung infection	Infections and infestations	—	—
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Pain	General disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Dry eye	Eye disorders	—	—
Headache	Nervous system disorders	—	—

Most-reported serious reactions: Laryngeal obstruction, Lung infection, Sudden death NOS.

Data from ClinicalTrials.gov NCT03707587 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting TGFβ signal transduction for cancer therapy.
   Liu S, Ren J, Ten Dijke P. · · 2021 · cited 302× · PMID 33414388 · DOI 10.1038/s41392-020-00436-9
2. Landscape of Myeloid-derived Suppressor Cell in Tumor Immunotherapy.
   Hao Z, Li R, Wang Y, Li S, et al · · 2021 · cited 72× · PMID 34689842 · DOI 10.1186/s40364-021-00333-5
3. New Insights Into the Role of Phenotypic Plasticity and EMT in Driving Cancer Progression.
   Bhatia S, Wang P, Toh A, Thompson EW. · · 2020 · cited 63× · PMID 32391381 · DOI 10.3389/fmolb.2020.00071
4. Targeting transforming growth factor-β signaling for enhanced cancer chemotherapy.
   Chen J, Ding ZY, Li S, Liu S, et al · · 2021 · cited 51× · PMID 33391538 · DOI 10.7150/thno.51383
5. Overcoming physical stromal barriers to cancer immunotherapy.
   Chung SW, Xie Y, Suk JS. · · 2021 · cited 20× · PMID 34351575 · DOI 10.1007/s13346-021-01036-y
6. Comprehensive multiomic characterization of human papillomavirus-driven recurrent respiratory papillomatosis reveals distinct molecular subtypes.
   Sievers C, Robbins Y, Bai K, Yang X, et al · · 2021 · cited 16× · PMID 34931021 · DOI 10.1038/s42003-021-02942-0
7. Dual PD-L1 and TGF-b blockade in patients with recurrent respiratory papillomatosis.
   Robbins Y, Friedman J, Clavijo PE, Sievers C, et al · · 2021 · cited 15× · PMID 34462327 · DOI 10.1136/jitc-2021-003113
8. Pulmonary manifestations of chronic HPV infection in patients with recurrent respiratory papillomatosis.
   Pai SI, Wasserman I, Ji YD, Gilman M, et al · · 2022 · cited 12× · PMID 35863360 · DOI 10.1016/s2213-2600(22)00008-x