NIH Clinical Center Search the Studies: Study Number, Study Title

Protocol Details

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

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: No longer recruiting/follow-up only
Gender: Male & Female
Min Age: 18 Years
Max Age: 120 Years

Referral Letter Required


Population Exclusion(s)

Pregnant Women;


HPV Associated Malignancy;
HPV Vaccine;

Recruitment Keyword(s)



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

Investigational Drug(s)


Investigational Device(s)



Biological/Vaccine: PRGN-2009 (Phase I)
Biological/Vaccine: M7824
Diagnostic Test: MRI
Diagnostic Test: Bone scan
Diagnostic Test: CT scan
Diagnostic Test: Brain CT
Diagnostic Test: Brain MRI
Procedure/Surgery: Biopsy (Phase I)

Supporting Site

National Cancer Institute


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.


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.


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)


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.

--Back to Top--



- 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.

- Adequate renal and hepatic function at screening, as follows:

--Serum creatinine =< 1.5 x upper limit of normal (ULN) OR Measured or calculated creatinine clearance >= 40 mL/min for participant with creatinine levels > 1.5 X institutional ULN (GFR can also be used in place of creatinine or CrCl);

--Bilirubin =< 1.5 x ULN OR in subjects with Gilbert s syndrome, a total bilirubin =< 3.0 x ULN;

--Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN, unless liver metastases are present, then values must be =< 3 x ULN).

- The effects of the immunotherapies (PRGN-2009 vaccine and M7824) on the developing human fetus are unknown. For this reason and because M7824 and PRGN-2009 used in this trial are possibly teratogenic, women of child-bearing potential and men must agree to use highly effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and up to 2 months following the last dose of M7824 study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

- Participants serologically positive for human immunodeficiency virus (HIV), Hep B, Hep C are eligible as long as the viral loads are undetectable by quantitative polymerase chain reaction (PCR). HIV positive participants must have cluster of differentiation 4 (CD4) count >= 200 cells per cubic millimeter at enrollment, be on stable antiretroviral therapy for at least 4 weeks and have no reported opportunistic infections or Castleman's disease within 12 months prior to enrollment.


- 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.

- Participants with pulse oximetry < 92% on room air at screening.

- Participants unable to provide informed consent.

- Participants whose inclusion in the trial would in the judgement of the principal investigator (PI) lead to time from diagnosis to initiation of curative treatment of>70 days (Arm 2A only).

--Back to Top--


Not Provided

--Back to Top--


Principal Investigator

Referral Contact

For more information:

Charalampos Floudas, M.D.
National Cancer Institute (NCI)
(240) 858-3032

NCIMO Referral Office
National Cancer Institute (NCI)

(888) 624-1937

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


--Back to Top--