What side effects are associated with this type of intervention?

Common treatments for Squamous Cell Carcinoma include Pembrolizumab, ISA101b, and Cisplatin-based chemoradiotherapy. Pembrolizumab, a PD-1 inhibitor, can cause side effects such as hypothyroidism, vitiligo-like lesions, and immune-related alopecia. ISA101b, an HPV-16 E6/E7 specific therapeutic vaccination, may have side effects similar to other immunotherapies, though specific data is limited. Cisplatin-based chemoradiotherapy often results in side effects like nausea, vomiting, nephrotoxicity, and ototoxicity, along with radiation-induced mucositis and dermatitis.

What prior FDA approvals exist?

Pembrolizumab, a PD-1 inhibitor, has received FDA approval for the treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. This approval expands the use of PD-1 inhibitors in treating SCC. Cisplatin-based chemoradiotherapy, which causes DNA damage and is used in combination with radiation, is a standard treatment for various forms of SCC, including head and neck cancers. While there is ongoing research into HPV-16 specific therapeutic vaccines like ISA101b, no such vaccines have yet received FDA approval for SCC treatment.

What other types of research exist?

Promising novel alternatives for Squamous Cell Carcinoma patients in 2024 include: 1) Immune checkpoint inhibitors such as Nivolumab and Cemiplimab, which have shown efficacy in clinical trials. 2) Therapeutic vaccines targeting other HPV strains or different tumor antigens. 3) Engineered T cells, including CAR-T cell therapies, which are in early development stages. 4) Antibody-drug conjugates that deliver cytotoxic agents directly to cancer cells. 5) Combination therapies that integrate multiple immunomodulatory agents or combine immunotherapy with conventional systemic therapy or radiation therapy.

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Alkylating agents

HPV Vaccine + Pembrolizumab + Cisplatin for Head and Neck Cancer

Phase 2

Waitlist Available

Led By Robert L Ferris, MD, PhD

Research Sponsored by Dan Zandberg

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

N2c/N3 disease irrespective of tobacco exposure

T4 or N2c/N3 disease irrespective of tobacco exposure

Must not have

Received prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.

Received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of a cancer vaccine, an immune-boosting drug, and standard treatments in adults with a specific type of head and neck cancer linked to HPV. The goal is to see if this combination improves patient survival.

Who is the study for?

This trial is for adults with newly diagnosed, intermediate risk HPV-16-associated head and neck squamous cell carcinoma without distant metastasis. Eligible patients must have a specific type of tumor in the oropharynx or unknown primary site, meet certain disease stage criteria, not have had prior treatments for head and neck cancer, be free from other cancers for at least 2 years (with some exceptions), and show adequate organ function.

What is being tested?

The study tests a new treatment combo: pembrolizumab (an immune therapy), ISA101b (HPV-16 vaccine), cisplatin (chemotherapy), and IMRT (targeted radiotherapy). It's designed to see if this mix can better treat local-regionally advanced head and neck cancer linked to HPV-16 compared to current standards.

What are the potential side effects?

Possible side effects include reactions related to the immune system such as inflammation in various organs, infusion-related reactions from pembrolizumab or ISA101b, chemotherapy-induced nausea/vomiting from cisplatin, skin irritation from IMRT, fatigue, blood disorders that may increase infection risk.

Eligibility Criteria

Inclusion Criteria

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

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My cancer has spread to lymph nodes, regardless of my smoking history.

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My cancer is advanced, regardless of my smoking history.

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My cancer is p16 positive and HPV positive but its primary location is unknown.

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My cancer is at a stage where surgery cannot cure it.

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I had a second head/neck cancer more than 2 years after the first, treated with surgery only, and it hasn't come back.

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I have not had radiation therapy above my collarbone.

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I have a history of significant smoking and advanced lymph node involvement.

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I am fully active or can carry out light work.

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I haven't had chemotherapy, targeted therapy, or radiation for head and neck cancer.

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I am 18 years old or older.

Exclusion Criteria

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

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I haven't had monoclonal antibody treatment in the last 4 weeks or have recovered from its side effects.

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I have been treated with specific immune system targeting drugs before.

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I have moderate to severe numbness, tingling, or pain in my hands or feet.

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I have serious lung conditions, including high blood pressure in my lungs or lung inflammation that needed steroids.

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I haven't taken antibiotics or antifungals for an infection in the last 7 days.

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I have an autoimmune disease that needed treatment in the last 3 months.

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I have a serious heart condition.

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My cancer originates in the mouth, voice box, lower throat, or upper throat.

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I have AIDS.

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I have been treated with anti-HPV drugs, not including vaccines.

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My cancer has not spread to distant parts of my body, including the brain.

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I have no severe allergies to medications or their ingredients.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Progression-free Survival (PFS) at 2 years

Secondary study objectives

Adverse Events Related to Study Treatment

Overall Survival (OS)

Progression-free Survival (PFS)

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Dysgeusia

33%

Vomiting

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Hypoacusis

20%

Alanine aminotransferase increased

20%

Hyponatraemia

19%

Tinnitus

19%

Oral candidiasis

19%

Asthenia

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hyperthyroidism

10%

Hypoalbuminaemia

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Neck pain

Peripheral sensory neuropathy

Gastrooesophageal reflux disease

Hiccups

Hyperglycaemia

Hyperuricaemia

Dizziness

Hypophosphataemia

Urinary tract infection

Ear pain

Localised oedema

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Sepsis

Pneumonia aspiration

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Clostridium difficile colitis

Systemic infection

Cardiac arrest

Death

Bronchitis

Hepatitis

Immune-mediated hepatitis

Oesophagitis

General physical health deterioration

Hypophagia

Tumour haemorrhage

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Colitis

Mouth haemorrhage

Hypersensitivity

Acute myocardial infarction

Abscess neck

Device related infection

Stoma site infection

Vascular device infection

Wound infection

Hypercalcaemia

Pulmonary embolism

Respiratory failure

100%

80%

60%

40%

20%

Study treatment Arm

Placebo + CRT Followed by Placebo

Pembrolizumab + CRT Followed by Pembrolizumab

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: IMRT + Pembrolizumab + Cisplatin + ISA101bExperimental Treatment4 Interventions

IMRT (Intensity Modulated Radiotherapy) of 70 Gy in 35 fractions over 7 weeks (5 fractions per week). Pembrolizumab will be administered at 200 mg (fixed dose) IV every 3 weeks (+/- 3 days), beginning beginning one week (week -1) prior to concurrent cisplatin-IMRT. Cisplatin will be administered at 100 mg/m2 IV on days 1(Week 0) and 22 (Week 3). ISA101b will be administered as three rounds of vaccination 3-4 weeks apart via two SC injections per vaccination round at 100ug/peptide, before pembrolizumab treatment. Vaccination #1 will be administered 1 week before pembrolizumab.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~2810

ISA101b

2021

Completed Phase 2

~120

Cisplatin

2013

Completed Phase 3

~3120

0 / 22Eligibility 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

Pembrolizumab, a PD-1 inhibitor, enhances the immune system's ability to recognize and attack cancer cells by blocking the PD-1 pathway. ISA101b, an HPV-16 E6/E7 specific therapeutic vaccine, stimulates the immune system to target and destroy cells expressing these viral proteins. Cisplatin-based chemoradiotherapy combines cisplatin, which causes DNA damage in cancer cells, with radiation therapy to further inhibit the cancer cells' ability to repair, leading to cell death. These treatments are significant for Squamous Cell Carcinoma patients as they provide targeted and effective strategies to combat the cancer, potentially improving outcomes and survival rates.

Novel immune-modulating drugs for advanced head and neck cancer.The forgotten woman's cancer: vulvar squamous cell carcinoma (VSCC) and a targeted approach to therapy.The State of Immune Checkpoint Inhibition in Urothelial Carcinoma: Current Evidence and Future Areas of Exploration.