What side effects are associated with this type of intervention?

Common treatments for Squamous Cell Carcinoma, particularly those involving PD-1 inhibitors like Cemiplimab and therapeutic cancer vaccines like ISA101b, are associated with several side effects. PD-1 inhibitors can cause immune-related adverse events such as skin reactions (rash, pruritus), gastrointestinal issues (diarrhea, colitis), liver inflammation (hepatitis), and endocrine disorders (thyroid dysfunction). Less common but serious side effects include pneumonitis and nephritis. Therapeutic cancer vaccines may lead to local injection site reactions, flu-like symptoms, and other immune-related effects. Combining these treatments may increase the likelihood or severity of these side effects.

What prior FDA approvals exist?

The FDA has approved several PD-1 inhibitors for the treatment of Squamous Cell Carcinoma, including pembrolizumab and nivolumab. Pembrolizumab has shown efficacy in both HPV-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) and is approved for use in patients with high PD-L1 expression. Nivolumab is also approved for previously treated HNSCC patients. While therapeutic cancer vaccines targeting HPV16 antigens, like ISA101b, are still under investigation, the combination of immunotherapy and targeted vaccines represents a promising approach in enhancing the immune response against HPV-related cancers.

What other types of research exist?

Promising alternatives to Cemiplimab plus ISA101b for Squamous Cell Carcinoma patients include: 1) Pembrolizumab (PD-1 inhibitor) which has shown efficacy in various cancers including head and neck SCC. 2) Nivolumab (PD-1 inhibitor) which has demonstrated improved overall survival in head and neck cancers. 3) Combination of Durvalumab (PD-L1 inhibitor) and Tremelimumab (CTLA-4 inhibitor) which has shown potential benefits in high tumor mutational burden cases. 4) Avelumab (PD-L1 inhibitor) which has shown durable responses in mesothelioma and could be considered for SCC. These alternatives offer different mechanisms of action and have shown promise in clinical trials.

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Checkpoint Inhibitor

Cemiplimab + ISA101b for HPV-Related Throat Cancer

Phase 2

Waitlist Available

Led By Bonnie S. Glisson, MD, BS

Research Sponsored by ISA Pharmaceuticals

Eligibility Criteria Checklist

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

Must have

Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

Sign and date an Institutional Review Board/Independent Ethics Committee (IRB)/(IEC)-approved written informed consent form (ICF) in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care

Must not have

Prior treatment with an anti-PD-1 antibody (e.g., nivolumab, pembrolizumab, cemiplimab), as well as an antibody targeting anti-PL-L1 anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co stimulation or immune checkpoint pathways

Subjects with known brain metastases or leptomeningeal metastases

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 25months

Summary

This trial is testing a combination of a cancer vaccine and a drug to help the immune system fight HPV16 positive oropharyngeal cancer. The vaccine teaches the immune system to attack cancer cells, and the drug keeps the immune system active. The vaccine targets cancers related to HPV, including cervical, oropharyngeal, and anal cancers.

Who is the study for?

Adults diagnosed with HPV16 positive recurrent or metastatic OPC (a type of throat cancer), whose tumors express a protein called PD-L1 and are suitable for first-line therapy with PD-1 blocking antibodies, or have progressed after chemotherapy. Participants must be in good physical condition (ECOG 0-1) and not have used certain immunosuppressive drugs recently. Women must test negative for pregnancy.

What is being tested?

This phase 2 trial is testing the effectiveness of Cemiplimab combined with ISA101b versus Cemiplimab with a placebo in treating HPV16-positive OPC. Patients will be randomly assigned to one of these two groups without knowing which treatment they receive.

What are the potential side effects?

Possible side effects include allergic reactions to the components of ISA101b or Cemiplimab, such as Montanide or cremophore, and typical immune-related adverse events from PD-1 inhibitors like skin reactions, hormonal changes, inflammation in organs, fatigue, and potential worsening of autoimmune conditions.

Eligibility Criteria

Inclusion Criteria

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

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I am fully active or can carry out light work.

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I have signed the consent form approved by the ethics committee.

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I am fully active or can carry out light work.

Exclusion Criteria

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

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I have previously been treated with specific immune-targeting cancer drugs.

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I have brain or leptomeningeal metastases.

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My cancer is HPV16 positive, has not been treated, cannot be surgically removed, does not respond to PD-1 antibody treatments.

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I have had more than one chemotherapy treatment for my advanced oral cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 25months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~25months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 25months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Overall Response Rate

Side effects data

From 2024 Phase 2 trial • 113 Patients • NCT04646005

39%

Injection site reaction

26%

Anaemia

23%

Nausea

19%

Pyrexia

19%

Fatigue

14%

Vomiting

12%

Abdominal pain

12%

Constipation

12%

Diarrhoea

12%

Asthenia

12%

Decreased appetite

10%

Pain in extremity

10%

Headache

Hypothyroidism

Arthralgia

Hyperthyroidism

Urinary tract infection

Oedema peripheral

Cough

Blood creatinine increased

Insomnia

Back pain

Infusion related reaction

Influenza like illness

Abdominal pain upper

Blood alkaline phosphatase increased

COVID-19

Aspartate aminotransferase increased

Dyspnoea

Vaginal haemorrhage

Pruritus

Hypotension

Sepsis

Device dislocation

Pneumonitis

Urosepsis

Acute kidney injury

Urogenital fistula

Respiratory failure

Female genital tract fistula

General physical health deterioration

Malaise

Chronic obstructive pulmonary disease

Cholecystitis

Acute myeloid leukaemia

Mental disorder

Actinic keratosis

Lymphoedema

Osteomyelitis

Pneumonia

Pulmonary tuberculosis

Pyelonephritis

Skin infection

Vaginal infection

Colitis

Colitis ischaemic

Dysphagia

Intestinal obstruction

Kidney infection

Skin bacterial infection

Intestinal perforation

Pancreatitis

Hydronephrosis

Renal haematoma

Urinary tract obstruction

100%

80%

60%

40%

20%

Study treatment Arm

ISA 101b + Cemiplimab 350 mg Q3W

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Active ISA101b and cemiplimab.Experimental Treatment2 Interventions

ISA101b 3 times plus cemiplimab every 3 weeks for up to 24 months

Group II: Placebo and cemiplimabPlacebo Group2 Interventions

Placebo 3 times plus cemiplimab every 3 weeks for up to 24 months

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

ISA101b

2021

Completed Phase 2

~120

Cemiplimab

2015

Completed Phase 3

~1450

0 / 7Eligibility 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

The most common treatments for Squamous Cell Carcinoma (SCC) include immunotherapy, particularly immune checkpoint inhibitors and therapeutic cancer vaccines. Cemiplimab, a PD-1 inhibitor, works by blocking the PD-1 pathway, which cancer cells often exploit to evade immune detection. By inhibiting this pathway, Cemiplimab enhances the immune system's ability to recognize and attack cancer cells. ISA101b is a therapeutic cancer vaccine targeting HPV16 antigens, designed to stimulate a robust immune response specifically against HPV16-positive cancer cells. These treatments are significant for SCC patients as they offer a targeted approach to boost the body's natural defenses against cancer, potentially leading to more effective and durable responses compared to traditional therapies.

Current Status of Clinical Trials for Cervical and Uterine Cancer Using Immunotherapy Combined With Radiation.Advances in immunotherapy for cervical cancer.The State of Immune Checkpoint Inhibition in Urothelial Carcinoma: Current Evidence and Future Areas of Exploration.