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

NCT ID: NCT04432597

Last Updated: 2025-12-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

39 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-11

Study Completion Date

2026-01-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

...

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Background

* Metastatic human papillomavirus (HPV) associated malignancies (cervical, anal, oropharyngeal cancers, etc.) are often incurable and poorly palliated by standard therapies.
* HPV-positive (p16+) oropharyngeal cancers are the most common HPV-associated malignancy in the United States and are increasing in incidence.
* Stage II and III HPV-positive oropharyngeal cancer is primarily treated with definitive therapy.
* Although the prognosis for stage I HPV+ oropharyngeal cancer is favorable, about 20 percent of patients with stage II disease and 35 percent of patients with stage III disease will die within four years.
* Attempts to de-intensify treatment of HPV-positive oropharyngeal cancer by replacing high-dose cisplatin with cetuximab concurrent with radiotherapy have failed.
* Induction and neoadjuvant immunotherapy are an area of active study in this type of cancer. The aims of induction immunotherapy are to induce antigen-specific immunity prior to definitive therapy and to reduce the risk of disease relapse for patients with stage II and III disease.
* Therapeutic vaccines targeting HPV alone or in combination with M7824 (MSB0011359C) (dual programmed death-ligand 1 (PD-L1) and transforming growth factor beta (TGF- beta) inhibitor) have demonstrated induction of HPV antigen-specific responses and tumor growth inhibition in multiple pre-clinical models of HPV-positive malignancy.
* In clinical studies done in the Center for Cancer Research (CCR), M7824 as monotherapy has produced a notable objective response rate (35-40%) for metastatic HPV + cancers including Oropharyngeal Squamous Cell Carcinoma (OPSCC) and preclinical studies support the addition of an investigational HPV vaccine with therapeutic intent (PRGN-2009, a gorilla adenoviral based vaccine) to further increase anti-tumor efficacy.

Objectives:

Phase I in participants with recurrent/metastatic HPV positive cancer:

-Primary objective: 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 every 2 weeks (q2w).

Phase II in participants with newly diagnosed stage I (T1, T2 N1)/II/III p16-positive oropharyngeal cancer and patients with newly diagnosed operable stage II/III/IVA/IVB/HPV + sinonasal squamous cell cancer:

-Primary objective: To determine if HPV vaccine alone (Arm 2A) is able to result in a \>= 2-fold increase in cluster of differentiation 3 (CD3+) tumor infiltrating T cells post treatment compared with pre-treatment in p16-positive oropharyngeal cancer.

Eligibility:

Phase I:

* Men or women of age \>= 18 years old.
* Subjects with cytologically or histologically confirmed locally advanced not amenable to potentially curative local therapies or metastatic HPV associated malignancies:

* 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+.
* Prior first line systemic therapy is required

Phase II:

* Men or women of age \>= 18 years old.
* Subjects with newly diagnosed stage I (T1, T2 N1), II or III, II or III p16-positive oropharyngeal squamous cell carcinoma (OPSCC) or stage II/III/IVA/IVB HPV-SNSCC planned for definitive therapy.

Design:

Phase I: Recurrent/metastatic HPV associated cancer:

* A 3+3 dose escalation design will be used which will evaluate PRGN-2009 (HPV vaccine) at two dose levels (1x10\^11 and 5x10\^11 viral particle (VP) units) given as monotherapy followed by a third dose level evaluating the RP2D dose of PRGN-2009 in combination with 1200 mg (RP2D) of M7824. In addition, the combination of PRGN-2009 at RP2D with 1200 mg of M7824 will be expanded to a total of 10 evaluable participants to gauge the preliminary efficacy of the combination of PRGN-2009 and M7824 in participants with advanced disease.
* There will be a 4-week dose limiting toxicity (DLT) evaluation period for each dose level.
* It is expected that up to 22 participants may enroll.

Phase II:

Newly diagnosed p16-positive oropharyngeal cancer:

* Evaluation of HPV vaccine alone (Arm 2A: Stage I (T1,T2 N1)/II/III) as neoadjuvant/ induction therapy before definitive standard of care therapy.
* Participants will receive neoadjuvant/ induction immunotherapy at National Institutes of Health (NIH) Clinical Center and then be referred back to their home institution for definitive standard of care therapy.
* It is expected that up to 20 participants may enroll.
* Newly diagnosed stage II/III/IVA/IVB HPV-SNSCC:
* Enrollment and treatment will occur similarly as participants with p16+oropharyngeal cancer for exploratory correlates to advise possible future trials. Up to 2 participants may enroll in this group.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

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

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

1/Arm 1A

Human Papillomavirus Vaccine (HPV) vaccine at 1x10(11) Viral Particles (VP) Dose Level 1 (DL1) and at 5x10(11) VP Dose Level 2 (DL2)

Group Type EXPERIMENTAL

PRGN-2009

Intervention Type BIOLOGICAL

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.

EKG

Intervention Type DIAGNOSTIC_TEST

Screening, end of treatment and follow-up.

Biopsy

Intervention Type PROCEDURE

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

CT Scan

Intervention Type DIAGNOSTIC_TEST

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.

MRI

Intervention Type DIAGNOSTIC_TEST

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

Brain CT

Intervention Type DRUG

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

Brain MRI

Intervention Type DRUG

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

Dexamethasone

Intervention Type DRUG

Dexamethasone 10mg for hypersensitivity reactions.

Epinephrine

Intervention Type DRUG

1:1,000 dilution for hypersensitivity reactions.

Diphenhydramine

Intervention Type DRUG

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

Ibuprofen

Intervention Type DRUG

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.

2/Arm 1B

Human Papillomavirus Vaccine (HPV) vaccine at recommended phase 2 dose (RP2D) plus M7824 at 1200 mg.

Group Type EXPERIMENTAL

PRGN-2009

Intervention Type BIOLOGICAL

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.

M7824

Intervention Type BIOLOGICAL

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.

EKG

Intervention Type DIAGNOSTIC_TEST

Screening, end of treatment and follow-up.

Biopsy

Intervention Type PROCEDURE

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

CT Scan

Intervention Type DIAGNOSTIC_TEST

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.

MRI

Intervention Type DIAGNOSTIC_TEST

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

Brain CT

Intervention Type DRUG

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

Brain MRI

Intervention Type DRUG

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

Dexamethasone

Intervention Type DRUG

Dexamethasone 10mg for hypersensitivity reactions.

Epinephrine

Intervention Type DRUG

1:1,000 dilution for hypersensitivity reactions.

Diphenhydramine

Intervention Type DRUG

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

Ibuprofen

Intervention Type DRUG

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.

3/Arm 2A

Human Papillomavirus Vaccine (HPV) vaccine at recommended phase 2 dose (RP2D) given as neoadjuvant or induction therapy.

Group Type EXPERIMENTAL

PRGN-2009

Intervention Type BIOLOGICAL

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.

EKG

Intervention Type DIAGNOSTIC_TEST

Screening, end of treatment and follow-up.

Biopsy

Intervention Type PROCEDURE

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

CT Scan

Intervention Type DIAGNOSTIC_TEST

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.

MRI

Intervention Type DIAGNOSTIC_TEST

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

Brain CT

Intervention Type DRUG

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

Brain MRI

Intervention Type DRUG

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

Dexamethasone

Intervention Type DRUG

Dexamethasone 10mg for hypersensitivity reactions.

Epinephrine

Intervention Type DRUG

1:1,000 dilution for hypersensitivity reactions.

Diphenhydramine

Intervention Type DRUG

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

Ibuprofen

Intervention Type DRUG

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.

4/Arm 2B

Human Papillomavirus Vaccine (HPV) vaccine at recommended phase 2 dose (RP2D) plus M7824 at 1200 mg given as neoadjuvant or induction therapy.

Group Type EXPERIMENTAL

PRGN-2009

Intervention Type BIOLOGICAL

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.

M7824

Intervention Type BIOLOGICAL

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.

EKG

Intervention Type DIAGNOSTIC_TEST

Screening, end of treatment and follow-up.

Biopsy

Intervention Type PROCEDURE

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

CT Scan

Intervention Type DIAGNOSTIC_TEST

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.

MRI

Intervention Type DIAGNOSTIC_TEST

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

Brain CT

Intervention Type DRUG

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

Brain MRI

Intervention Type DRUG

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

Dexamethasone

Intervention Type DRUG

Dexamethasone 10mg for hypersensitivity reactions.

Epinephrine

Intervention Type DRUG

1:1,000 dilution for hypersensitivity reactions.

Diphenhydramine

Intervention Type DRUG

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

Ibuprofen

Intervention Type DRUG

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type 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.

Intervention Type BIOLOGICAL

EKG

Screening, end of treatment and follow-up.

Intervention Type DIAGNOSTIC_TEST

Biopsy

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

Intervention Type PROCEDURE

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.

Intervention Type DIAGNOSTIC_TEST

MRI

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

Intervention Type DIAGNOSTIC_TEST

Brain CT

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

Intervention Type DRUG

Brain MRI

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

Intervention Type DRUG

Dexamethasone

Dexamethasone 10mg for hypersensitivity reactions.

Intervention Type DRUG

Epinephrine

1:1,000 dilution for hypersensitivity reactions.

Intervention Type DRUG

Diphenhydramine

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

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

MSB0011359C Electrocardiogram Bx Computed tomography Magnetic resonance imaging Brain computed tomography Brain magnetic resonance imaging Decadron Ozurdex Dexycu Adrenaline Benadryl Advil Motrin IB Midol IB

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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.

Exclusion Criteria

* 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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Charalampos Floudas, MD, DMSc, MS

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Charalampos Floudas, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 40116923 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form: Phase I Participants Consent

View Document

Document Type: Informed Consent Form: Phase II Participants Consent

View Document

Related Links

Access external resources that provide additional context or updates about the study.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

20-C-0104

Identifier Type: -

Identifier Source: secondary_id

200104

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.