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 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:
Blood, urine, and heart tests
Possible photos of skin lesions
CT, 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.
Metastatic 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
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 (dual PD-L1 and
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 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.
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 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 squamos cell cancer:
-Primary objective: To determine if either HPV vaccine alone (Arm 2A) or in combination with
M7824 (Arm 2B) is able to result in a >= 2-fold increase in CD3+ tumor infiltrating T cells
post treatment compared with pre-treatment in p16-positive oropharyngeal cancer.
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:
p16+ Oropharyngeal cancers;
Vulvar, vaginal, penile, and squamous cell rectal cancers
Other locally advanced or metastatic solid tumors (e.g. lung, esophagus) that are
Prior first line systemic therapy is required
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.
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
There will be a 4-week DLT evaluation period for each dose level.
It is expected that up to 22 participants may enroll in 6 months.
Sequential two-arm evaluation of HPV vaccine alone (Arm 2A: Stage I (T1,T2 N1)/II/III)
or HPV vaccine plus M7824 (Arm 2B: Stage II/III) as neoadjuvant/ induction therapy
before definitive standard of care therapy (20 participants each arm).
Participants will receive neoadjuvant/ induction immunotherapy at NIH Clinical Center
and then be referred back to their home institution for definitive standard of care
It is expected that up to 40 participants may enroll in 2 years.
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 4 participants
may enroll in this group.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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