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Bifunctional Fusion Protein

Combination Immunotherapy for Human Papillomavirus Cancers

Phase 1 & 2
Waitlist Available
Led By Julius Y Strauss, M.D.
Research Sponsored by National Cancer Institute (NCI)
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Participants serologically positive for HIV, Hep B, Hep C are eligible as long as the viral loads are undetectable by quantitative PCR. HIV positive participants must have CD4 count >= 200 cells per cubic millimeter at enrollment, be on stable antiretroviral therapy for at least 4 weeks and have no reported opportunistic infections or castleman s disease within 12 months prior to enrollment.
Subjects with cytologically or histologically confirmed locally advanced or metastatic HPV associated malignancies: Cervical cancers; P16+ Oropharyngeal cancers; Anal cancers; Vulvar, vaginal, penile, and squamous cell rectal cancers; Other locally advanced or metastatic solid tumors (e.g., lung, esophagus) that are known HPV+.
Timeline
Screening 3 weeks
Treatment Varies
Follow Up every 2 months, up to approximately 10 months
Awards & highlights

Study Summary

This trial is testing a combination of immunotherapy drugs to see if they can help people with HPV-associated cancers.

Who is the study for?
Adults with advanced HPV-related cancers, including cervical, oropharyngeal, anal, vulvar, vaginal, penile and certain lung or esophageal cancers. Participants must have had one prior chemotherapy and checkpoint therapy if FDA-approved for their cancer type (exceptions apply). They need adequate organ function and an ECOG status <=2. Pregnant women are excluded.Check my eligibility
What is being tested?
The trial tests a combination of immunotherapy drugs: PDS0101 injected under the skin every 4 weeks then quarterly; M7824 infused every 2 weeks; NHS-IL12 injected monthly. The treatment lasts up to a year with regular NIH visits and lifelong follow-ups after completion.See study design
What are the potential side effects?
Potential side effects include reactions at injection sites, flu-like symptoms from immune activation (fever, chills), fatigue, changes in blood counts affecting immunity and clotting risk. Organ inflammation is possible due to immune system overactivity.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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I have HIV or Hepatitis with undetectable viral load and stable health.
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My cancer is HPV-related and in an advanced or metastatic stage.
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I've had one round of chemo and, if approved for my cancer type, checkpoint therapy.
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I am using or willing to use effective birth control during and for two months after the study.
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I've had one round of chemo and, if approved for my cancer type, checkpoint therapy.
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My kidney and liver functions are within the required range.
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I can take care of myself but might not be able to do heavy physical work.
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I can take care of myself but might not be able to do heavy physical work.
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My condition is anal cancer.
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I am 18 years old or older.
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I am 18 years old or older.
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My cancer is HPV positive and has spread beyond its original location.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~every 2 months, up to approximately 10 months
This trial's timeline: 3 weeks for screening, Varies for treatment, and every 2 months, up to approximately 10 months for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.
Primary outcome measures
Best Overall Response (BOR) in Checkpoint Naive and Immune Checkpoint Blockade (ICB) Resistant Disease in Participants With Advanced or Metastatic Human Papillomavirus (HPV) Associated Malignancies
Secondary outcome measures
Duration of Response (DOR)
Number of Participants With Grades 1, 2, 3, 4 and/or 5 Treatment Related Adverse Events
Number of Treatment Related Grades 1, 2, 3, 4 and/or 5 Adverse Events
+3 more
Other outcome measures
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

Side effects data

From 2023 Phase 1 & 2 trial • 21 Patients • NCT04247282
43%
Oral hemorrhage
36%
Constipation
36%
Fatigue
36%
Lymphocyte count decreased
36%
Epistaxis
29%
Dysphagia
29%
Weight loss
21%
Hyperglycemia
21%
Pruritus
21%
Wound infection
21%
Anemia
14%
Hyperthyroidism
14%
Lipase increased
14%
Rash acneiform
14%
White blood cell decreased
14%
Creatinine increased
14%
Gait disturbance
14%
Rash maculo-papular
14%
Tumor hemorrhage
14%
Alanine aminotransferase increased
14%
Oral pain
7%
Palpitations
7%
Aspartate aminotransferase increased
7%
Blood bilirubin increased
7%
Cough
7%
Flu like symptoms
7%
Hyponatremia
7%
Hypoxia
7%
Intraoperative head and neck injury
7%
Vaccination site lymphadenopathy
7%
Gastrointestinal disorders - Other, Sialadenitis
7%
Hematuria
7%
Respiratory failure
7%
Atrial fibrillation
7%
CPK increased
7%
Dermatitis radiation
7%
GGT increased
7%
Hypermagnesemia
7%
Hypophosphatemia
7%
Nausea
7%
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify
7%
Peripheral sensory neuropathy
7%
Aphonia
7%
Dehydration
7%
Edema limbs
7%
Mucositis oral
7%
Tumor pain
7%
Lung infection
7%
Sinus tachycardia
7%
Vasculitis
7%
Alkaline phosphatase increased
7%
Dysarthria
7%
Dysesthesia
7%
Dysgeusia
7%
Hypothyroidism
7%
Pain
7%
Skin ulceration
7%
Stroke
100%
80%
60%
40%
20%
0%
Study treatment Arm
Arm A, Cohort 1 Bintrafusp Alfa (M7824) 1200 mg (Days 1, 15)
Arm B,Cohort 1 M7824 1200mg+TriAdVaccine 5x10e^11viral Particles(ETBX-011,ETBX-051&ETBX-061) (Day 1)
Arm C, Cohort 1 M7824 1200mg + TriAd Vaccine 5x10e^11 Viral Particles (Day 1)+N-803 15mcg/kg (Day 1)

Trial Design

2Treatment groups
Experimental Treatment
Group I: Cohort 2, Arm 2: Cervical Cancer With Prior Pelvic Radiation and Boost BrachytherapyExperimental Treatment3 Interventions
Triple Therapy: PDS0101 + NHS-IL12 + M7824 (MSB0011395C); PDS0101 + NHS-IL12 + M7824; Reduced doses. May enroll up to 12 participants for a safety evaluation and up to 12 additional participants for preliminary evaluation of efficacy and further evaluation of safety.
Group II: Cohort 1, Arm 1: Human Papillomavirus (HPV) Associated MalignanciesExperimental Treatment3 Interventions
Triple Therapy: PDS0101 + NHS-IL12 + M7824 (MSB0011395C); The dose level of NHS-IL12 may decrease depending on dose limiting toxicity (DLT) events. The dose level of human papillomavirus vaccine (HPV) vaccine and M7824 will remain constant. If more than 3 of 8 participants have an objective response then accrual will be expanded to 20 evaluable participants.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
M7824
2020
Completed Phase 2
~350

Find a Location

Who is running the clinical trial?

National Cancer Institute (NCI)Lead Sponsor
13,609 Previous Clinical Trials
40,915,595 Total Patients Enrolled
Julius Y Strauss, M.D.Principal InvestigatorNational Cancer Institute (NCI)
5 Previous Clinical Trials
237 Total Patients Enrolled
Charalampos Floudas, M.D.Principal InvestigatorNational Cancer Institute (NCI)
5 Previous Clinical Trials
630 Total Patients Enrolled

Media Library

M7824 (Bifunctional Fusion Protein) Clinical Trial Eligibility Overview. Trial Name: NCT04287868 — Phase 1 & 2
Human Papillomavirus Cancers Research Study Groups: Cohort 2, Arm 2: Cervical Cancer With Prior Pelvic Radiation and Boost Brachytherapy, Cohort 1, Arm 1: Human Papillomavirus (HPV) Associated Malignancies
Human Papillomavirus Cancers Clinical Trial 2023: M7824 Highlights & Side Effects. Trial Name: NCT04287868 — Phase 1 & 2
M7824 (Bifunctional Fusion Protein) 2023 Treatment Timeline for Medical Study. Trial Name: NCT04287868 — Phase 1 & 2

Frequently Asked Questions

These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

What is the maximum capacity of enrollees in this clinical trial?

"Absolutely. According to clinicaltrials.gov, this research project is currently recruiting participants who were first posted on June 9th 2020 and last modified on November 29th 2022. The trial requires the enlistment of 56 individuals from 1 medical centre."

Answered by AI

Are individuals currently eligible to partake in this experiment?

"Affirmative. The information available on clinicaltrials.gov attests to the fact that this research endeavour is actively trying to recruit volunteers; it was initially posted on June 9th 2020 and updated lastly November 29th 2022. Specifically, 56 participants are wanted from 1 site for the study's duration."

Answered by AI

Who else is applying?

What state do they live in?
Tennessee
How old are they?
18 - 65
What site did they apply to?
National Institutes of Health Clinical Center
What portion of applicants met pre-screening criteria?
Met criteria
~11 spots leftby Mar 2025