Recruitment

Recruitment Status
Recruiting
Estimated Enrollment
29

Summary

Conditions
  • Anal Cancer
  • Cervical Cancer
  • HPV Cancers
  • 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 or refractory/recurrent HPV associated malignancies (cervical, anal, oropharyngeal cancers etc.) are poorly palliated by standard therapies. There is an unmet need for active treatments for these tumors. In a phase I trial of M7824 (NCT02517398) 15 out of 43 (34.9%) patients w...

Background: Metastatic or refractory/recurrent HPV associated malignancies (cervical, anal, oropharyngeal cancers etc.) are poorly palliated by standard therapies. There is an unmet need for active treatments for these tumors. In a phase I trial of M7824 (NCT02517398) 15 out of 43 (34.9%) patients with HPV associated malignancies had radiographic tumor responses according to RECIST 1.1 or iRECIST. While the response rate observed with M7824 appears to be higher than single agent PD-1 inhibitors alone (15-20%), the majority of patients with these diseases still do not seem to benefit from immunotherapy. Preclinical studies suggest that the use of a combination of multiple immunotherapy agents may have improved anti-tumor efficacy. Specifically, preclinical studies have shown that the combination of three immunotherapy agents (1) a therapeutic vaccine against HPV positive cancers (PDS0101), (2) a bifunctional fusion protein targeting PD-L1 and TGF beta (M7824), and (3) a tumor targeted immunocytokine (NHS-IL12) produces greater anti-tumor activity than any single or dual combination of these agents. Objectives: - To evaluate the objective response rate (ORR) according to Response Evaluation Criteria (RECIST 1.1) of the combination of (1) a therapeutic vaccine against HPV positive cancers (PDS0101), (2) a tumor targeted immunocytokine (NHS-IL12) and (3) a bifunctional fusion protein targeting PD-L1 and TGF beta (M7824) in subjects with checkpoint naive advanced HPV associated malignancies. Eligibility: 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 patient declines standard treatment after appropriate counseling has been provided. Subjects must have measurable disease. Design: This is a phase I/II trial of combination immunotherapy. The trial will be conducted using a Simon optimal two-stage design. Participants will receive HPV vaccine + NHS-IL12 + M7824. The first six participants will be evaluable for dose limiting toxicities (DLTs) and accrual will only continue to 8 participants who have not been treated with checkpoint inhibitors if less than 2 out of the first 6 participants experience a DLT. If three or more out of eight participants who have not been treated with checkpoint inhibitors have objective responses accrual will be expanded to enroll 20 evaluable participants. Patients with cervical cancer with prior pelvic radiation and boost brachytherapy will be enrolled in a separate cohort to evaluate safety and preliminary evidence of efficacy.

Tracking Information

NCT #
NCT04287868
Collaborators
Not Provided
Investigators
Principal Investigator: Julius Y Strauss, M.D. National Cancer Institute (NCI)