HPV Vaccine PRGN-2009 Alone or in Combination With Anti-PDL1/TGF-Beta Trap (M7824) in Subjects With HPV Associated Cancers

Summary

Background:

For some cancers associated with human papillomavirus (HPV), standard treatments are not helpful. Researchers want to see if a vaccine for HPV combined with a drug called M7824 (MSB0011359C) has a better effect on these cancers than when they work alone.

Objective:

To find a safe dose of HPV vaccine alone or combined with M7824. Also, to test if either HPV vaccine alone or combined with M7824 causes a better immune response.

Eligibility:

People ages 18 and older with locally advanced or metastatic HPV associated cancer (Phase I) or stage II or III p16-positive oropharyngeal cancer (Phase II)

Design:

Participants will be screened with:

Medical history

Physical exam

Blood, urine, and heart tests

Possible photos of skin lesions

Computed tomography (CT), magnetic resonance imaging (MRI), or nuclear bone scan: Participants will lie in a machine that takes pictures of the body. For the CT scan, they may have a contrast agent injected into a vein.

Participants may have up to 2 tumor biopsies. For participants in Phase II, this may be performed with a thin tube placed through the nose into the airway.

Participants will receive the HPV vaccine alone or with M7824. For participants on the Phase II, they will receive two doses of HPV vaccine under the skin either alone or with M7824 as an infusion spaced two weeks apart. This will be done prior to their planned chemoradiation or surgery. For participants on the Phase I, they will get the HPV vaccine injected under the skin 2 to 3 times in the first month. Then they will have a booster every 4 weeks. They will receive M7824 as an infusion into a vein every 2 weeks. Treatment will last up to 1 year.

After they stop treatment, participants will have a visit within 4 weeks. They will then be contacted for long-term follow-up every year, for the rest of their lives.

...

Conditions

• HPV Positive Cancer
• Vulvar, Vaginal, Penile, Rectal Cancer
• Anal Cancer
• Oropharyngeal Cancer
• Cervical Cancer

Interventions

BIOLOGICAL

PRGN-2009

On the phase I portion of the protocol PRGN-2009 will be administered on Day (D)1, D15, D29 followed by booster vaccines every 4 weeks for up to a year. The dose level given as booster will be the same dose participants will be receiving for D1, D15 and D29. On the phase II portion of the protocol PRGN-2009 will be administered on just D1 and D15 for Cohort 1/Arm 1A, Cohort 2/Arm 1B, Cohort 3/Arm 2A, and Cohort 4/Arm2B.

BIOLOGICAL

M7824

Subjects enrolled to Cohort 2/Arm 1B will receive M7824 (MSB0011359C) via intravenous (IV) infusion over 1 hour (-10 minutes / +20 minutes, that is, over 50 to 80 minutes) once every 2 weeks. M7824 will be administered as a "flat" dose of 1,200 mg independent of body weight. M7824 is administered as an intravenous infusion with a mandatory 0.2 micron in-line filter.

DIAGNOSTIC_TEST

EKG

Screening, end of treatment and follow-up.

PROCEDURE

Biopsy

For immune analysis: Baseline Day 1 and odd numbered weeks (week(W) 1, W3, W5, W7 onwards.

DIAGNOSTIC_TEST

CT Scan

CT scan chest, abdomen, pelvis, neck, and/or skull as clinically indicated. Tumor evaluation at screening, baseline Day 1, odd numbered weeks (week(W) 1, W3, W5, W7 onwards. Long term follow-up.

DIAGNOSTIC_TEST

MRI

Tumor evaluation at screening, baseline Day 1, odd numbered weeks (week(W) 1, W3, W5, W7 onwards. Long term follow-up.

DRUG

Brain CT

Screening. As clinically indicated in participants with known central nervous system (CNS) disease.

DRUG

Brain MRI

Screening. As clinically indicated in participants with known central nervous system (CNS) disease.

DRUG

Dexamethasone

Dexamethasone 10mg for hypersensitivity reactions.

DRUG

Epinephrine

1:1,000 dilution for hypersensitivity reactions.

DRUG

Diphenhydramine

Antihistamines (e.g., Diphenhydramine) given intravenously for allergy.

DRUG

Ibuprofen

For flu-like symptoms. 400mg or comparable Nonsteroidal anti-inflammatory drugs (NSAID) dose, may be administered 2 hours before and 8 hours after the start of each intravenous infusion.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Charalampos Floudas, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-08-11

Primary Completion

2022-11-22

Completion

2026-05-29

FDA Drug

Yes

Countries

• United States

Study Locations