HPV Vaccine PRGN-2009 Alone or in Combination With Anti-PDL1/TGF-Beta Trap (M7824) in Subjects With HPV Associated Cancers
Phase I/II Trial of HPV Vaccine PRGN-2009 Alone or in Combination With Anti-PD-L1/TGF-Beta Trap (M7824) in Subjects With HPV Positive Cancers
2 other identifiers
interventional
39
1 country
1
Brief 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. ...
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Aug 2020
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 13, 2020
CompletedFirst Posted
Study publicly available on registry
June 16, 2020
CompletedStudy Start
First participant enrolled
August 11, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 22, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
March 31, 2026
CompletedFebruary 17, 2026
February 1, 2026
2.3 years
June 13, 2020
February 12, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Safety and recommended phase II dose of PRGN-2009
Phase I: In participants with recurrent/metastatic HPV positive cancer - To determine the safety and recommended phase II dose (RP2D) of PRGN-2009 (HPV vaccine) alone or in combination with M7824 administered at RP2D of 1200 mg q2w.
one year
Level increase in CD3+ tumor infiltrating T cells post-treatment compared to pre-treatment
Phase II: In participants with newly diagnosed stage I (T1,T2 N1)/II/III p16-positive oropharyngeal cancer - To determine if HPV vaccine alone (Arm 2A) is able to result in a equal to or greater than 2-fold increase in CD3+ tumor infiltrating T cells post treatment compared with pre-treatment in p16-positive oropharyngeal cancer.
one year
Secondary Outcomes (8)
ratio of participants that are hospitalized because of adverse events attributed to disease progression
study end
3-year overall and relapse-free survival rate for PRGN-2009 alone
study end
overall survival (OS)
study end
progression-free survival time (PFS)
study end
duration of response
study end
- +3 more secondary outcomes
Study Arms (4)
1/Arm 1A
EXPERIMENTALHuman Papillomavirus Vaccine (HPV) vaccine at 1x10(11) Viral Particles (VP) Dose Level 1 (DL1) and at 5x10(11) VP Dose Level 2 (DL2)
2/Arm 1B
EXPERIMENTALHuman Papillomavirus Vaccine (HPV) vaccine at recommended phase 2 dose (RP2D) plus M7824 at 1200 mg.
3/Arm 2A
EXPERIMENTALHuman Papillomavirus Vaccine (HPV) vaccine at recommended phase 2 dose (RP2D) given as neoadjuvant or induction therapy.
4/Arm 2B
EXPERIMENTALHuman Papillomavirus Vaccine (HPV) vaccine at recommended phase 2 dose (RP2D) plus M7824 at 1200 mg given as neoadjuvant or induction therapy.
Interventions
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.
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.
Screening, end of treatment and follow-up.
For immune analysis: Baseline Day 1 and odd numbered weeks (week(W) 1, W3, W5, W7 onwards.
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.
Tumor evaluation at screening, baseline Day 1, odd numbered weeks (week(W) 1, W3, W5, W7 onwards. Long term follow-up.
Screening. As clinically indicated in participants with known central nervous system (CNS) disease.
Screening. As clinically indicated in participants with known central nervous system (CNS) disease.
Dexamethasone 10mg for hypersensitivity reactions.
1:1,000 dilution for hypersensitivity reactions.
Antihistamines (e.g., Diphenhydramine) given intravenously for allergy.
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.
Eligibility Criteria
You may qualify if:
- Subjects with cytologically or histologically confirmed locally advanced not amenable to potentially curative local therapies or metastatic human papillomavirus (HPV) associated malignancies (Phase I only):
- Cervical cancers;
- p16+ Oropharyngeal cancers;
- Anal cancers;
- Vulvar, vaginal, penile, and squamous cell rectal cancers;
- Other locally advanced or metastatic solid tumors (e.g., lung, esophagus) that are known HPV+.
- Subjects with cytologically or histologically confirmed newly diagnosed stage II or III p16-positive oropharyngeal squamous cell carcinoma planned for definitive therapy or with newly diagnosed stage II or III or IVA or IVB HPV-positive sinonasal squamous carcinoma (HPV-SNSCC) eligible for primary surgery (Phase II only).
- Subjects must have measurable disease, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Phase 1 only).
- Phase I only: Participants must have received one prior line of systemic chemotherapy in the recurrent/metastatic setting as well as checkpoint blockade therapy in tumors with Food and Drug Administration (FDA) approval (head and neck squamous cell cancer and programmed death-ligand 1 (PDL1+) cervical cancer). Exceptions to this include participants not eligible to receive standard therapy.
- Men or Women; Age \>=18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
- Adequate hematologic function at screening, as follows:
- Absolute neutrophil count (ANC) \>=1 x 109/L;
- Hemoglobin \>= 9 g/dL;
- Platelets \>= 75,000/microliter.
- +6 more criteria
You may not qualify if:
- Participants with prior investigational drug, live vaccine, chemotherapy, immunotherapy or any prior radiotherapy (except for palliative bone directed therapy) within the past 28 days prior to the first drug administration except if the investigator has assessed that all residual treatment-related toxicities have resolved or are minimal and feel the participant is otherwise suitable for enrollment. Participants may continue adjuvant hormonal therapy in the setting of a definitively treated cancer (e.g., breast).
- Major surgery within 28 days prior to the first drug administration (minimally invasive procedures such as diagnostic biopsies are permitted).
- Known active brain or central nervous system metastasis (less than a month out from definitive radiotherapy or surgery), seizures requiring anticonvulsant treatment (\<3 months) or clinically significant cerebrovascular accident (\<3 months). In order to be eligible participants must have repeated central nervous system (CNS) imaging at least a month after definitive treatment showing stable CNS disease. Participants with evidence of intra-tumoral or peritumoral hemorrhage on baseline imaging are also excluded unless the hemorrhage is grade =\< 1 and has been shown to be stable on two consecutive imaging scans.
- 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.
- Only for Phase I, Arm 1B: Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent with exception of:
- Diabetes type I, eczema, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease or other mild autoimmune disorders not requiring immunosuppressive treatment;
- Administration of steroids for other conditions through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is acceptable;
- Subjects on systemic intravenous or oral corticosteroid therapy with the exception of
- physiologic doses of corticosteroids (=\< the equivalent of prednisone 10 mg/day) or other immunosuppressors such as azathioprine or cyclosporin A are excluded on the basis of potential immune suppression. For these subjects these excluded treatments must be discontinued at least 1 weeks prior to enrollment for recent short course use (=\< 14 days) or discontinued at least 4 weeks prior to enrollment for long term use (\> 14 days). In addition, the use of corticosteroids as premedication for contrast-enhanced studies is allowed prior to enrollment and on study.
- Only for Phase I: Subjects with a history of serious intercurrent chronic or acute illness, such as cardiac or pulmonary disease, hepatic disease, bleeding diathesis or recent (within 3 months) clinically significant bleeding events, known left ventricular ejection fraction \<50% (confirmation of ejection fraction (EF) \> 50% is not required for eligibility), history of myocarditis, or recent myocardial infarction (within 6 months), or other illness considered by the Investigator as high risk for M7824 drug treatment.
- Only for Phase I: Subjects refusing to accept blood products as medically indicated.
- History of second malignancy within 3 years of enrollment except for the following: adequately treated localized skin cancer, cervical carcinoma in situ, superficial bladder cancer, other localized malignancy which has been adequately treated or malignancy which does not require active systemic treatment (e.g., low risk chronic lymphocytic leukemia (CLL)). For participants enrolled on the phase I portion of the protocol a second HPV driven malignancy is allowed.
- Only for Phase I, Arm 1B: Subjects with a known severe hypersensitivity reaction to monoclonal antibodies or its excipients (grade \>/= 3 National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v5) will be evaluated by the allergy/immunology team prior to enrollment.
- Prior allogenic tissue/solid organ transplant.
- For participants who may receive M7824: previous life-threatening side effects resulting from prior checkpoint inhibitor therapy.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Publications (1)
Floudas CS, Goswami M, Donahue RN, Strauss J, Pastor DM, Redman JM, Brownell I, Turkbey EB, Steinberg SM, Cordes LM, Marte JL, Khan MH, McMahon S, Lamping E, Manu M, Manukyan M, Brough DE, Lankford A, Jochems C, Schlom J, Gulley JL. PRGN-2009 and bintrafusp alfa for patients with advanced or metastatic human papillomavirus-associated cancer. Cancer Immunol Immunother. 2025 Mar 21;74(5):155. doi: 10.1007/s00262-025-04009-z.
PMID: 40116923DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Charalampos Floudas, M.D.
National Cancer Institute (NCI)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
June 13, 2020
First Posted
June 16, 2020
Study Start
August 11, 2020
Primary Completion
November 22, 2022
Study Completion
March 31, 2026
Last Updated
February 17, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
- Access Criteria
- Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.
All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).