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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

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.

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 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

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%

Insomnia

11%

Hypothyroidism

11%

Rash maculo-papular

11%

Constipation

11%

Hypoalbuminaemia

10%

Epistaxis

Oedema peripheral

Vomiting

Headache

Hyperglycaemia

Dizziness

Keratoacanthoma

Lipase increased

Hyponatraemia

Myalgia

Urinary tract infection

Hypotension

Weight decreased

Pneumonia

Dry Skin

Blood bilirubin increased

Blood creatinine increased

Upper respiratory tract infection

Amylase increased

Hyperuricaemia

Hyperkeratosis

Rash pruritic

Productive cough

Back pain

Chest pain

Hyperthyroidism

Disease progression

Hypomagnesaemia

Hypokalaemia

Pneumothorax

Squamous cell carcinoma of skin

Dyspepsia

Hypertension

Pulmonary haemorrhage

Keratoacanthom

Abdominal pain upper

Skin toxicity

Blood thyroid stimulating hormone increased

Fluid overload

Troponin increased

Skin infection

Myopathy

Death

Stevens-Johnson syndrome

Sudden death

Bladder cancer

Cancer pain

Tumour haemorrhage

Acute myocardial infarction

Infusion related reaction

Platelet count decreased

Aplastic anaemia

Autoimmune haemolytic anaemia

Fall

Iron deficiency anaemia

Oesophageal ulcer

Arrhythmia

Influenza

Hypercalcaemia

Coronary artery disease

Malaise

Infection

Pneumonia staphylococcal

Fractured sacrum

Chronic obstructive pulmonary disease

Hypoxia

Pleural effusion

Pneumonitis

Drug eruption

Eczema

Toxic skin eruption

Embolism

Superior vena cava syndrome

Agranulocytosis

Angina pectoris

Fracture pain

Spondylitis

Cerebral infarction

Renal failure

Lichen planus

Immune-mediated enterocolitis

Pericardial effusion

Immune thrombocytopenia

Adrenal insufficiency

Oral candidiasis

Bile duct stone

Cholecystitis

Immune-mediated nephritis

Aortic aneurysm

Transaminases increased

Bacterial sepsis

Bronchitis

Strangulated incisional hernia

Thoracic vertebral fracture

Encephalitis

Pulmonary sepsis

Diabetes mellitus

Sciatica

Asthma

Dermatitis bullous

Hypersensitivity

Cholestasis

Hyperthermia

Hepatotoxicity

Lower respiratory tract infection

Colitis

Viral upper respiratory tract infection

Urinary tract infection bacterial

Pancreatitis

General physical health deterioration

Duodenitis

Upper gastrointestinal haemorrhage

Gastric ulcer haemorrhage

Gastrointestinal haemorrhage

Hepatitis

Hip fracture

Bladder transitional cell carcinoma

Erythema

Pemphigoid

Respiratory failure

Interstitial lung disease

Erythema multiforme

Orthostatic hypotension

100%

80%

60%

40%

20%

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

~660

NHS-IL12

2020

Completed Phase 2

~40