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

Cervical Cancer Clinical Trial

Official title: 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

Status Active, not recruiting

Clinical Trial 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.

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Clinical Trial Description

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. ;

Related Conditions & MeSH terms

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

• NCT number: NCT04432597
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: August 11, 2020
• Completion date: November 20, 2025