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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
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+.
Adequate renal and hepatic function at screening, as follows: Serum creatinine <= 1.5 x upper limit of normal (ULN) OR Measured or calculated creatinine clearance >=40 mL/min for participant with creatinine levels > 1.5 X institutional ULN (GFR can also be used in place of creatinine or CrCl); Bilirubin <= 1.5 x ULN OR in subjects with Gilbert's syndrome, a total bilirubin <= 3.0 x ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 x ULN, unless liver metastases are present, then values must be <= 3 x ULN).
Must not have
Known intolerance to or life threatening side effects resulting from prior checkpoint inhibitor therapy.
Pregnant women are excluded from this study because these drugs have not been tested in pregnant women and there is potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these immunotherapies, breastfeeding should be discontinued if the mother is treated on this protocol.
Timeline
Screening 3 weeks
Treatment Varies
Follow Up every 2 months, up to approximately 10 months
Awards & highlights

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.
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.
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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My cancer is HPV-related and in an advanced or metastatic stage.
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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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My condition is anal cancer.
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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.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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I had severe reactions to previous immunotherapy.
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I am not pregnant or breastfeeding.
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I am willing to accept blood products if needed.
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I haven't had major surgery in the last 28 days.
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I have not had chemotherapy that weakens my immune system or any organ transplant.

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

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
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 study objectives
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 study objectives
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 2024 Phase 3 trial • 304 Patients • NCT03631706
34%
Pruritus
32%
Rash
30%
Anaemia
20%
Fatigue
19%
Dyspnoea
19%
Pyrexia
18%
Haemoptysis
17%
Asthenia
17%
Decreased appetite
16%
Diarrhoea
15%
Aspartate aminotransferase increased
15%
Cough
13%
Gamma-glutamyltransferase increased
13%
Arthralgia
13%
Nausea
13%
Alanine aminotransferase increased
12%
Blood alkaline phosphatase increased
11%
Hypothyroidism
11%
Insomnia
11%
Rash maculo-papular
11%
Constipation
11%
Hypoalbuminaemia
10%
Epistaxis
9%
Oedema peripheral
9%
Vomiting
9%
Headache
9%
Hyperglycaemia
8%
Dizziness
8%
Lipase increased
8%
Keratoacanthoma
7%
Hyponatraemia
7%
Myalgia
7%
Urinary tract infection
7%
Hypotension
7%
Weight decreased
6%
Pneumonia
6%
Dry Skin
6%
Blood bilirubin increased
6%
Blood creatinine increased
6%
Upper respiratory tract infection
6%
Amylase increased
6%
Hyperuricaemia
5%
Hyperkeratosis
5%
Rash pruritic
5%
Productive cough
5%
Back pain
5%
Chest pain
4%
Hyperthyroidism
4%
Disease progression
3%
Hypomagnesaemia
3%
Hypokalaemia
3%
Pneumothorax
3%
Squamous cell carcinoma of skin
3%
Dyspepsia
2%
Hypertension
2%
Pulmonary haemorrhage
2%
Keratoacanthom
2%
Abdominal pain upper
1%
Fluid overload
1%
Sudden death
1%
Acute myocardial infarction
1%
Infusion related reaction
1%
Platelet count decreased
1%
Aplastic anaemia
1%
Autoimmune haemolytic anaemia
1%
Fall
1%
Iron deficiency anaemia
1%
Oesophageal ulcer
1%
Death
1%
Arrhythmia
1%
Influenza
1%
Skin infection
1%
Myopathy
1%
Hypercalcaemia
1%
Troponin increased
1%
Bladder cancer
1%
Cancer pain
1%
Tumour haemorrhage
1%
Skin toxicity
1%
Stevens-Johnson syndrome
1%
Blood thyroid stimulating hormone increased
1%
Coronary artery disease
1%
Malaise
1%
Infection
1%
Pneumonia staphylococcal
1%
Fractured sacrum
1%
Chronic obstructive pulmonary disease
1%
Hypoxia
1%
Pleural effusion
1%
Pneumonitis
1%
Drug eruption
1%
Eczema
1%
Toxic skin eruption
1%
Embolism
1%
Superior vena cava syndrome
1%
Agranulocytosis
1%
Angina pectoris
1%
Fracture pain
1%
Spondylitis
1%
Cerebral infarction
1%
Renal failure
1%
Lichen planus
1%
Immune-mediated enterocolitis
1%
Pericardial effusion
1%
Immune thrombocytopenia
1%
Adrenal insufficiency
1%
Oral candidiasis
1%
Bile duct stone
1%
Cholecystitis
1%
Immune-mediated nephritis
1%
Aortic aneurysm
1%
Transaminases increased
1%
Bacterial sepsis
1%
Bronchitis
1%
Strangulated incisional hernia
1%
Thoracic vertebral fracture
1%
Encephalitis
1%
Pulmonary sepsis
1%
Diabetes mellitus
1%
Sciatica
1%
Asthma
1%
Dermatitis bullous
1%
Hypersensitivity
1%
Cholestasis
1%
Hyperthermia
1%
Hepatotoxicity
1%
Lower respiratory tract infection
1%
Colitis
1%
Viral upper respiratory tract infection
1%
Urinary tract infection bacterial
1%
Pancreatitis
1%
General physical health deterioration
1%
Duodenitis
1%
Upper gastrointestinal haemorrhage
1%
Gastric ulcer haemorrhage
1%
Gastrointestinal haemorrhage
1%
Hepatitis
1%
Hip fracture
1%
Bladder transitional cell carcinoma
1%
Erythema
1%
Pemphigoid
1%
Respiratory failure
1%
Interstitial lung disease
1%
Erythema multiforme
1%
Orthostatic hypotension
100%
80%
60%
40%
20%
0%
Study treatment Arm
M7824
Pembrolizumab

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
2018
Completed Phase 3
~660

Find a Location

Who is running the clinical trial?

National Cancer Institute (NCI)Lead Sponsor
13,842 Previous Clinical Trials
41,002,949 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
634 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 1, Arm 1: Human Papillomavirus (HPV) Associated Malignancies, Cohort 2, Arm 2: Cervical Cancer With Prior Pelvic Radiation and Boost Brachytherapy
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
~10 spots leftby Sep 2025
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