Recruitment

Recruitment Status
Recruiting
Estimated Enrollment
70

Summary

Conditions
  • Anal Cancer
  • Cervical Cancer
  • HPV Positive Cancer
  • Oropharyngeal Cancer
  • Vulvar, Vaginal, Penile, Rectal Cancer
Type
Interventional
Phase
Phase 1Phase 2
Design
Allocation: Non-RandomizedIntervention Model: Sequential AssignmentMasking: None (Open Label)Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

Description

Background 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...

Background 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 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 highdose 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. 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 q2w. Phase II in participants with newly diagnosed stage 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 ^3 2-fold increase in 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 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 unless the participant declines standard treatment after appropriate counseling has been provided. Phase II: Men or women of age >= 18 years old. Subjects with newly diagnosed stage 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 to the 11th power and 5x10 to the 11th power 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 DLT evaluation period for each dose level. It is expected that up to 22 participants may enroll in 6 months. Phase II: Newly diagnosed stage II/III p16-positive oropharyngeal cancer: Sequential two-arm evaluation of HPV vaccine alone (Arm 2A) or HPV vaccine plus M7824 (Arm 2B) 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 therapy. 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.

Tracking Information

NCT #
NCT04432597
Collaborators
Not Provided
Investigators
Principal Investigator: Charalampos Floudas, M.D. National Cancer Institute (NCI)