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Bifunctional Fusion Protein
Combination Immunotherapy for Human Papillomavirus Cancers
Bethesda, MD
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
No Placebo-Only Group
Summary
This trial is testing a combination of immunotherapy drugs to see if they can help people with HPV-associated cancers.
See full description
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 belowSelect...
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.
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Exclusion Criteria
You may be eligible for the trial if you check “No” for criteria below:Select...
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.
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Timeline
Screening ~ 3 weeks3 visits
Treatment ~ Varies
Follow Up ~ every 2 months, up to approximately 10 months
Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~every 2 months, up to approximately 10 months
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 moreOther 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 • NCT0363170634%
Pruritus
32%
Rash
30%
Anaemia
20%
Fatigue
19%
Pyrexia
19%
Dyspnoea
18%
Haemoptysis
17%
Asthenia
17%
Decreased appetite
16%
Diarrhoea
15%
Aspartate aminotransferase increased
15%
Cough
13%
Nausea
13%
Gamma-glutamyltransferase increased
13%
Arthralgia
13%
Alanine aminotransferase increased
12%
Blood alkaline phosphatase increased
11%
Hypothyroidism
11%
Constipation
11%
Hypoalbuminaemia
11%
Insomnia
11%
Rash maculo-papular
10%
Epistaxis
9%
Vomiting
9%
Oedema peripheral
9%
Hyperglycaemia
9%
Headache
8%
Lipase increased
8%
Keratoacanthoma
8%
Dizziness
7%
Weight decreased
7%
Hyponatraemia
7%
Hypotension
7%
Urinary tract infection
7%
Myalgia
6%
Blood bilirubin increased
6%
Blood creatinine increased
6%
Hyperuricaemia
6%
Dry Skin
6%
Pneumonia
6%
Upper respiratory tract infection
6%
Amylase increased
5%
Chest pain
5%
Back pain
5%
Productive cough
5%
Hyperkeratosis
5%
Rash pruritic
4%
Disease progression
4%
Hyperthyroidism
3%
Squamous cell carcinoma of skin
3%
Dyspepsia
3%
Hypokalaemia
3%
Hypomagnesaemia
3%
Pneumothorax
2%
Abdominal pain upper
2%
Hypertension
2%
Keratoacanthom
2%
Pulmonary haemorrhage
1%
Acute myocardial infarction
1%
Coronary artery disease
1%
Angina pectoris
1%
Arrhythmia
1%
Death
1%
General physical health deterioration
1%
Hyperthermia
1%
Malaise
1%
Sudden death
1%
Bile duct stone
1%
Cholecystitis
1%
Cholestasis
1%
Hepatitis
1%
Pericardial effusion
1%
Colitis
1%
Duodenitis
1%
Gastric ulcer haemorrhage
1%
Gastrointestinal haemorrhage
1%
Hepatotoxicity
1%
Hypersensitivity
1%
Bacterial sepsis
1%
Bronchitis
1%
Encephalitis
1%
Infection
1%
Influenza
1%
Lower respiratory tract infection
1%
Urinary tract infection bacterial
1%
Viral upper respiratory tract infection
1%
Fall
1%
Fractured sacrum
1%
Hip fracture
1%
Diabetes mellitus
1%
Fluid overload
1%
Hypercalcaemia
1%
Fracture pain
1%
Myopathy
1%
Spondylitis
1%
Bladder cancer
1%
Bladder transitional cell carcinoma
1%
Tumour haemorrhage
1%
Cerebral infarction
1%
Sciatica
1%
Immune-mediated nephritis
1%
Renal failure
1%
Asthma
1%
Chronic obstructive pulmonary disease
1%
Hypoxia
1%
Dermatitis bullous
1%
Drug eruption
1%
Erythema
1%
Erythema multiforme
1%
Lichen planus
1%
Pemphigoid
1%
Skin toxicity
1%
Stevens-Johnson syndrome
1%
Toxic skin eruption
1%
Aortic aneurysm
1%
Embolism
1%
Orthostatic hypotension
1%
Superior vena cava syndrome
1%
Blood thyroid stimulating hormone increased
1%
Immune thrombocytopenia
1%
Iron deficiency anaemia
1%
Pulmonary sepsis
1%
Eczema
1%
Immune-mediated enterocolitis
1%
Pancreatitis
1%
Oesophageal ulcer
1%
Upper gastrointestinal haemorrhage
1%
Oral candidiasis
1%
Pneumonia staphylococcal
1%
Skin infection
1%
Infusion related reaction
1%
Strangulated incisional hernia
1%
Thoracic vertebral fracture
1%
Platelet count decreased
1%
Transaminases increased
1%
Troponin increased
1%
Cancer pain
1%
Interstitial lung disease
1%
Pleural effusion
1%
Pneumonitis
1%
Respiratory failure
1%
Aplastic anaemia
1%
Autoimmune haemolytic anaemia
1%
Agranulocytosis
1%
Adrenal insufficiency
100%
80%
60%
40%
20%
0%
Study treatment Arm
M7824
Pembrolizumab
Awards & Highlights
No Placebo-Only Group
All patients enrolled in this study will receive some form of active treatment.
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
~710
NHS-IL12
2020
Completed Phase 2
~40
Find a Location
Closest Location:National Institutes of Health Clinical Center· Bethesda, MD
Who is running the clinical trial?
National Cancer Institute (NCI)Lead Sponsor
14,068 Previous Clinical Trials
41,160,052 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
644 Total Patients Enrolled
Media Library
Eligibility Criteria:
This trial includes the following eligibility criteria:- I have HIV or Hepatitis with undetectable viral load and stable health.My cancer is HPV-related and in an advanced or metastatic stage.I had severe reactions to previous immunotherapy.I've had one round of chemo and, if approved for my cancer type, checkpoint therapy.I haven't had cancer treatments except for hormone therapy or palliative bone therapy in the last 28 days.I am not pregnant or breastfeeding.I am using or willing to use effective birth control during and for two months after the study.My kidney and liver functions are within the required range.My brain or CNS cancer has been stable for over a month after treatment.I've had one round of chemo and, if approved for my cancer type, checkpoint therapy.I have a mild autoimmune disease or am on low-dose steroids not for immune suppression.I can take care of myself but might not be able to do heavy physical work.My condition is anal cancer.I am willing to accept blood products if needed.I haven't had major surgery in the last 28 days.I haven't had a cancer related to HPV in the last 3 years, except for a local one that's been treated or one not needing active treatment.I have had a severe allergic reaction to monoclonal antibodies.I have not had chemotherapy that weakens my immune system or any organ transplant.I am 18 years old or older.My cancer is HPV positive and has spread beyond its original location.
Research Study Groups:
This trial has the following groups:- Group 1: Cohort 1, Arm 1: Human Papillomavirus (HPV) Associated Malignancies
- Group 2: Cohort 2, Arm 2: Cervical Cancer With Prior Pelvic Radiation and Boost Brachytherapy
Awards:
This trial has 1 awards, including:- No Placebo-Only Group - All patients enrolled in this study will receive some form of active treatment.
Timeline:
This trial has the following timeline:- Screening: It may take up to 3 Weeks to process to see if you qualify in this trial.
- Treatment: The duration you will receive the treatment varies.
- Follow Ups: You may be asked to continue sharing information regarding the trial for 6 Months after you stop receiving the treatment.