What side effects are associated with this type of intervention?

Common side effects of cancer treatments similar to the HPV vaccine and M7824 include immune-related adverse events such as fatigue, rash, diarrhea, and pruritus. Severe side effects can include pneumonitis, colitis, hepatitis, and endocrinopathies, which may require immunosuppressive treatment. Vaccines may also cause local reactions at the injection site, fever, and flu-like symptoms.

What prior FDA approvals exist?

The FDA has approved several immunotherapy agents and vaccines for the treatment of various cancers. Pembrolizumab, an immune checkpoint inhibitor, is approved for use in multiple cancers, including melanoma and head and neck cancers, and has shown efficacy in HPV-associated cancers. Nivolumab, another checkpoint inhibitor, is approved for melanoma, head and neck cancers, and other malignancies. Both drugs work by blocking the PD-1 pathway, enhancing the immune system's ability to fight cancer. Additionally, the FDA has approved the HPV vaccine for preventing HPV-related cancers, such as cervical cancer. These approvals highlight the growing role of immunotherapy and vaccines in cancer treatment.

What other types of research exist?

Promising alternatives to the HPV vaccine and M7824 for cancer treatment include: 1) Pembrolizumab (Keytruda), an anti-PD-1 therapy, which has shown efficacy in various cancers including cervical and head and neck cancers. 2) Nivolumab (Opdivo), another anti-PD-1 therapy, effective in head and neck squamous cell carcinoma. 3) Cemiplimab (Libtayo), an anti-PD-1 therapy, showing promise in recurrent cervical cancer. 4) Talimogene laherparepvec (T-VEC), an oncolytic virus therapy, which promotes intratumoral T cell infiltration and enhances response to anti-PD-1 therapy. These therapies represent significant advancements in the treatment of HPV-associated cancers.

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Cancer Vaccine

HPV Vaccine + M7824 for HPV-Associated Cancers

Q: What is the mechanism of action of this treatment?

Immunotherapy and vaccines are pivotal in modern cancer treatment. Immunotherapy, including agents like PD-1/PD-L1 inhibitors, enhances the immune system's ability to detect and destroy cancer cells by blocking mechanisms that allow tumors to evade immune surveillance. Vaccines, such as the HPV vaccine, stimulate the immune system to recognize and attack cancer-associated antigens, preventing or treating cancers linked to those antigens. These approaches are crucial for cancer patients as they provide targeted, personalized treatment options that can improve efficacy and reduce side effects compared to conventional therapies.

Phase 1 & 2

Waitlist Available

Led By Charalampos Floudas, 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

p16+ Oropharyngeal cancers

Anal cancers;

Must not have

Major surgery within 28 days prior to the first drug administration (minimally invasive procedures such as diagnostic biopsies are permitted).

Pregnant women are excluded from this study because M7824 and PRGN-2009 vaccine 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 one year

Awards & highlights

No Placebo-Only Group

Summary

This trial tests an HPV vaccine alone or with a drug called M7824. It targets adults with advanced HPV-related cancers or newly diagnosed stage II/III p16-positive oropharyngeal cancer. The vaccine helps the immune system recognize cancer cells, and M7824 makes it harder for these cells to hide from the immune system.

Who is the study for?

Adults (18+) with advanced or metastatic HPV-associated cancers, including cervical, anal, and p16-positive oropharyngeal cancers. Participants must have measurable disease and an ECOG performance status of <=2. Prior treatments are allowed under specific conditions. Adequate organ function is required, and effective contraception must be used.

What is being tested?

The trial tests the safety and immune response to an HPV vaccine alone or combined with M7824 in patients with HPV-related cancers. Phase I involves multiple vaccine doses plus bi-weekly M7824 infusions for up to a year; Phase II precedes chemoradiation/surgery with two vaccine doses alone or with M7824.

What are the potential side effects?

Potential side effects include typical reactions at the injection site from vaccines, as well as more serious risks associated with immunotherapy such as inflammation in various organs, infusion reactions similar to allergic responses, fatigue, possible blood disorders, and increased risk of infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My throat cancer is p16 positive.

Select...

My cancer is located in the anal region.

Select...

My cervical cancer is advanced and cannot be cured with surgery or radiation.

Select...

I have a newly diagnosed HPV-positive throat or sinonasal cancer at stage II, III, IVA, or IVB.

Select...

I can take care of myself but might not be able to do heavy physical work.

Select...

My cancer is advanced, spreads to other parts, and is HPV positive.

Select...

My condition is anal cancer.

Select...

My kidney function, measured by creatinine or GFR, is within the required range.

Select...

My cancer is in the vulva, vagina, penis, or rectum.

Select...

My throat cancer is p16 positive.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I haven't had major surgery in the last 28 days.

Select...

I am not pregnant or breastfeeding.

Select...

I am able to understand and agree to the study's procedures and risks.

Select...

I have had a transplant of tissue or an organ from another person.

Select...

I refuse to accept blood products even if needed for my treatment.

Select...

I have a serious illness like heart or liver disease that could make treatment risky.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ one year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~one year

This trial's timeline: 3 weeks for screening, Varies for treatment, and one year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Level increase in CD3+ tumor infiltrating T cells post-treatment compared to pre-treatment

Safety and recommended phase II dose of PRGN-2009

Secondary study objectives

3-year overall and relapse-free survival rate for PRGN-2009 alone

assess the safety of the recommended phase II dose (RP2D) of PRGN-2009 (HPV vaccine) alone

does the use of PRGN-2009 alone result in significantly prolonged survival

+5 more

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

Blood thyroid stimulating hormone increased

Fluid overload

Troponin increased

Skin infection

Myopathy

Skin toxicity

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

4Treatment groups

Experimental Treatment

Group I: 4/Arm 2BExperimental Treatment8 Interventions

Human Papillomavirus Vaccine (HPV) vaccine at recommended phase 2 dose (RP2D) plus M7824 at 1200 mg given as neoadjuvant or induction therapy.

Group II: 3/Arm 2AExperimental Treatment8 Interventions

Human Papillomavirus Vaccine (HPV) vaccine at recommended phase 2 dose (RP2D) given as neoadjuvant or induction therapy.

Group III: 2/Arm 1BExperimental Treatment8 Interventions

Human Papillomavirus Vaccine (HPV) vaccine at recommended phase 2 dose (RP2D) plus M7824 at 1200 mg.

Group IV: 1/Arm 1AExperimental Treatment7 Interventions

Human Papillomavirus Vaccine (HPV) vaccine at 1x10(11) Viral Particles (VP) Dose Level 1 (DL1) and at 5x10(11) VP Dose Level 2 (DL2)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

MRI

2009

Completed Phase 2

~2810

Brain MRI

2013

Completed Phase 4

~930

Bone scan

2015

Completed Phase 2

~250

CT scan

2013

Completed Phase 2

~2450

M7824

2018

Completed Phase 3

~660

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Immunotherapy and vaccines are pivotal in modern cancer treatment. Immunotherapy, including agents like PD-1/PD-L1 inhibitors, enhances the immune system's ability to detect and destroy cancer cells by blocking mechanisms that allow tumors to evade immune surveillance. Vaccines, such as the HPV vaccine, stimulate the immune system to recognize and attack cancer-associated antigens, preventing or treating cancers linked to those antigens. These approaches are crucial for cancer patients as they provide targeted, personalized treatment options that can improve efficacy and reduce side effects compared to conventional therapies.

Targeting HPV in gynaecological cancers - Current status, ongoing challenges and future directions.