Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Antineoplastic Agents

All Drugs and Chemicals

Cemiplimab

Antineoplastic Agents, Immunological

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

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

ISA101b

Placebo

Bonnie S. Glisson, MD, BS

This will be a blinded, placebo-controlled, randomized, phase 2 study in which subjects will be randomly assigned 1:1 to cemiplimab plus placebo or cemiplimab plus ISA101b.

This study will assess the ability of ISA101b to improve Overall Response Rate in subjects with HPV16 positive OPC, when combined with cemiplimab, an investigational anti-PD-1 antibody being developed by Regeneron Pharmaceuticals. ISA101b is a therapeutic cancer vaccine that induces specific immune responses to the oncogenic E6 and E7 antigens from HPV16. Trials in HPV16 driven malignancies indicate it has activity in HPV16 driven malignancies including oropharyngeal and cervical cancers. Cemiplimab, also known as REGN2810, is in late stage trials and appears to have similar activity to approved anti PD-1 antibodies in a number of malignancies .

A Randomized Phase 2 Study of Cemiplimab ± ISA101b in HPV16-Positive OPC

A Randomized, Double-blind, Placebo-Controlled, Phase 2 Study of Cemiplimab Versus the Combination of Cemiplimab With ISA101b in the Treatment of Subjects With HPV16-Positive Oropharyngeal Cancer (OPC)

Regeneron Pharmaceuticals

ISA Pharmaceuticals

Symptoms and General Pathology

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Neoplasm Metastasis

Lip Neoplasms

Oropharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Mouth Neoplasms

Mouth Diseases

Oral Cancer

Utomilumab by vein every 4 weeks for up to 12 doses beginning on Cycle 1 Day 1.

ISA101b as an injection under the skin every 4 weeks for 3 doses. Participants receive 2 injections each time.

Utomilumab given by vein on Cycle 1 Day 1. Cycle 1-2 100 mg, Cycle 3-12 50 mg until progressive disease, toxicity, or 1 yr.

Utomilumab

ISA101b 100 mcg/peptide given subcutaneously every 4 weeks x 3 doses beginning cycle 1 day 1.

Bonnie S. Glisson, BS,MD

The goal of this clinical research study is to learn if utomilumab, when given with ISA101b, is able to shrink or slow the growth of tumors in patients with incurable HPV+ oropharyngeal squamous cell carcinoma.

This is an investigational study. Utomilumab and ISA101b are not FDA approved or commercially available. They are currently being used for research purposes only. The study doctor can explain how the study drugs are designed to work.

Up to 27 participants will be enrolled. All will take part at MD Anderson.

Study Drug Administration:

There are 28 days in each study cycle.

You will receive utomilumab by vein every 4 weeks for up to 12 doses beginning on Cycle 1 Day 1. The drug will be given over about 1 hour each time you receive it.

You will receive ISA101b as an injection under the skin every 4 weeks for 3 doses. You will receive 2 injections each time. One may be in your arm and one in your leg.

Length of Study:

You may continue taking utomilumab for up to 1 year as long as your doctor thinks it is in your best interest. You will no longer be able to take the study drug(s) if intolerable side effects occur or if you are unable to follow study directions. You may not be able to take the study drug(s) if the disease gets worse, which is explained below.

Your participation on the study will be over after the follow-up visits.

Study Visits:

On Day 1 of Cycles 1-12:

* You will have a physical exam.
* Blood (about 1 tablespoon) will be collected for routine tests, thyroid function tests, and liver function tests.
* If you can become pregnant, blood (about ½ teaspoon) or urine will be collected for a pregnancy test.
* During Cycles 1, 2, 3, 4, 8, and 12, blood (up to 10 tablespoons) will be drawn for biomarker testing (including genetic biomarkers).

At the end of Cycle 2 and every 8 weeks after that, you will have an MRI or CT scan to check the status of the disease.

Study Continuation:

If the disease appears to have gotten worse, you may still be eligible to continue receiving your assigned study drug(s). This is because you may be benefitting from the study drug(s) even though the tumor(s) got larger. Your doctor will discuss this with you.

If this happens, your doctor will talk to you about whether or not you want to continue. If you do continue taking part in the study, you will follow the study visits as described above.

However, there are risks of continuing to receive the study drug(s) because the disease may actually be getting worse. You are still at risk for side effects due to utomilumab and ISA101b. Continuing on this study could also delay starting other treatments. The disease may get worse to the point that you are no longer able to receive other treatments. There are also risks from the additional tests that may be performed, such as biopsies and blood draws. You and your doctor will discuss these possible risks, and you will be asked to decide if you want to continue receiving the study drug(s).

End-of-Treatment and Follow-up Visits:

At about 30 days after your last study drug dose:

* You will have a physical exam.
* Blood (about 1 tablespoon) will be collected for routine tests, thyroid function tests, and liver function tests.
* If you are able to become pregnant, blood (about ½ teaspoon) or urine will be collected for a pregnancy test.

At about 70 days after your last study drug dose:

* You will have a physical exam.
* Blood (about 1 tablespoon) will be collected for routine tests, thyroid function tests, and liver function tests.
* If you are able to become pregnant, blood (about ½ teaspoon) or urine will be collected for a pregnancy test.

You will also be called every 3 months up to 1½ years and asked about your health. Each call should last about 10-15 minutes.

If you stopped taking the study drug for reasons other than the disease getting worse, you will continue to have MRI/CT scans every 8 weeks. If the disease appears to get worse, or you start a new anticancer therapy, these scans will stop.

Utomilumab and ISA101b Vaccination in Patients With HPV-16-Positive Incurable Oropharyngeal Cancer

Phase II Trial of Utomilumab and ISA101b Vaccination in Patients With HPV-16-Positive Incurable Oropharyngeal Cancer

Overall Response Rate assessed by RECIST 1.1 Criteria

Adverse events assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for grades 1-3.

Response rate monitored by radiographic assessment.

PFS defined as the time from first day of treatment to the date of the first documented tumor progression (per RECIST 1.1), or death due to any cause.

ISA Pharmaceuticals B.V.

Pfizer

M.D. Anderson Cancer Center

Treatment with Utomilumab every 4 weeks and 3 doses of ISA101b Vaccination for every 4 weeks first 3 cycles in Patients with HPV-16-Positive Incurable Oropharynx Cancer

Utomilumab and ISA101b

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

All participants who signed the consent are included in the baseline characteristics.

Dr. John Heymach, PHD-Chair, Thoracic-Head & Neck Med Onc

Overall Response Rate (ORR) of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)

Grade 1

Grade 2

Grade 3

Adverse Events of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)

No data collected for Response Rate by irRC of Utomilumab Combined with ISA 101b in Patients with Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC).

Response Rate by irRC of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)

Progression Free Survival (PFS) of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)

Overall Study

Squamous Cell Carcinoma of Head and Neck

Pembrolizumab

Antibodies

Antibodies, Monoclonal

Vaccines

Cisplatin

Immunoglobulins

Immune Checkpoint Inhibitors

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.

IMRT (Intensity Modulated Radiotherapy)

A potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between programmed cell death protein 1 (PD-1) and its ligands, PD-L1 and PD-L2.

ISA101b is a therapeutic cancer vaccine that induces specific immune responses to the oncogenic E6 and E7 antigens from HPV16.

Jennifer Ruth, RN, BSN

Dan P Zandberg, MD

This clinical trial will evaluate a new combination of pembrolizumab, HPV-16 E6/E7 specific therapeutic vaccination (ISA101b) and cisplatin-based chemoradiotherapy for patients with newly diagnosed, local-regionally advanced, intermediate risk HPV-associated head and neck squamous cell carcinoma.

This study aims to enroll adult male and female patients who have intermediate risk disease with histologically-confirmed head and neck squamous cell carcinoma (HNSCC) with no evidence of distant metastasis. All patients will receive the same treatment and there is no active control group.

In this trial, patients will undergo biopsy followed by treatment with the ISA101b vaccine which targets human papillomavirus (HPV). The vaccine treatment will begin 2 weeks prior to cisplatin and Intensity-Modulated Radiation Therapy (cisplatin-IMRT) and one week prior to the first dose of pembrolizumab, an anti-cancer immunotherapy targeting PD-1. The vaccine will be administered 2 additional times at weeks 2 and 5. Pembrolizumab will be initiated 1 week prior to cisplatin-IMRT at the dose of 200 mg IV q3 weeks (+/- 3 days). Pembrolizumab will be continued concurrently through cisplatin-IMRT (weeks 3, 6 ), and continued for a 15 week maintenance period after completion of cisplatin-IMRT for a total pembrolizumab treatment period of 24 weeks (8 doses; 6 months).

The purpose of this study is to evaluate patient survival following this combination of treatments.

HPV-16 Vaccination and Pembrolizumab Plus Cisplatin for "Intermediate Risk" HPV-16-associated Head and Neck Squamous Cell Carcinoma

Phase II Study Evaluating HPV-16 Vaccination (ISA101b) and Pembrolizumab Plus Cisplatin Chemoradiotherapy for "Intermediate Risk" HPV-16 Associated Head and Neck Squamous Cell Carcinoma (HNSCC)

The proportion of participants whose disease has to progressed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at 2 years. PFS will be calculated from treatment initiation to disease progression or death from any cause for 2 years. Per RECIST 1.1, Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

The percentage of Serious Adverse Events per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 that are possibly, probably or definitely related to study treatment.

The length of time during and after the treatment that patients remain alive with disease that does not progress. PFS will be calculated from treatment initiation to disease progression or death from any cause or last follow up. Per RECIST 1.1, Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

The length of time (months) from the initiation of treatment that patients are still alive.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Randomized Phase 2 Study of Cemiplimab ± ISA101b in HPV16-Positive OPC	NCT03669718	Squamous Cell C... HPV16 Positive	ISA101b Cemiplimab Placebo	18 Years -	ISA Pharmaceuticals
Utomilumab and ISA101b Vaccination in Patients With HPV-16-Positive Incurable Oropharyngeal Cancer	NCT03258008	Malignant Neopl... Malignant Neopl... Oropharyngeal C...	Utomilumab ISA101b	18 Years -	M.D. Anderson Cancer Center
HPV-16 Vaccination and Pembrolizumab Plus Cisplatin for "Intermediate Risk" HPV-16-associated Head and Neck Squamous Cell Carcinoma	NCT04369937	HPV-Related Squ... Head and Neck S...	IMRT (Intensity... Pembrolizumab Cisplatin ISA101b	18 Years -	University of Pittsburgh

Spots Global Cancer Trial Database for isa101b

Every month we try and update this database with for isa101b cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for isa101b

Every month we try and update this database with for isa101b cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for isa101b cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.