Ignite Creation Date:
2025-12-24 @ 5:58 PM
Ignite Modification Date:
2025-12-24 @ 5:58 PM
Study NCT ID:
NCT04287868
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-04-13
First Post:
2020-02-26
Is Possible Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
Phase I/II Trial of Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background:
More than 30,000 cases of human papillomavirus (HPV) associated cancers occur annually in the United States. When these cancers spread, they do not respond well to standard treatments and are often incurable. Researchers want to see if a mix of drugs can help.
Objective:
To learn if a mix of immunotherapy drugs can shrink tumors in people with HPV associated cancers.
Eligibility:
People ages 18 and older with locally advanced or metastatic HPV associated cancer, such as cervical cancers; cyclin-dependent kinase inhibitor 2A (P16+) oropharyngeal cancers; anal cancers; vulvar, vaginal, penile, and squamous cell rectal cancers; or other locally advanced or metastatic solid tumors (e.g., lung, esophagus) that are known HPV+ cancers
Design:
Participants will be screened with:
* medical history
* disease confirmation (or tumor biopsy)
* physical exam
* body scans (computed tomography (CT), magnetic resonance imaging (MRI), and/or nuclear)
* blood tests
* electrocardiogram (to measure the electrical activity of the heart)
* urine tests.
Participants will get PDS0101 injected under the skin every 4 weeks for 6 doses. Then they will get it every 3 months for 2 doses.
Participants will get M7824 (MSB0011395C) by intravenous infusion every 2 weeks. For this, a needle is inserted into a vein. The drug is given over a 1-hour period.
Participants will get NHS-IL12 injected under the skin every 4 weeks.
Participants will get the study drugs for up to 1 year. They will visit the NIH every 2 weeks. They will repeat the screening tests during the study.
About 28 days after treatment ends, participants will have a follow-up visit or telephone call. Then they will be contacted every 3 months for 1 year, and then every 6 months after that, for the rest of their life.
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...
More than 30,000 cases of human papillomavirus (HPV) associated cancers occur annually in the United States. When these cancers spread, they do not respond well to standard treatments and are often incurable. Researchers want to see if a mix of drugs can help.
Objective:
To learn if a mix of immunotherapy drugs can shrink tumors in people with HPV associated cancers.
Eligibility:
People ages 18 and older with locally advanced or metastatic HPV associated cancer, such as cervical cancers; cyclin-dependent kinase inhibitor 2A (P16+) oropharyngeal cancers; anal cancers; vulvar, vaginal, penile, and squamous cell rectal cancers; or other locally advanced or metastatic solid tumors (e.g., lung, esophagus) that are known HPV+ cancers
Design:
Participants will be screened with:
* medical history
* disease confirmation (or tumor biopsy)
* physical exam
* body scans (computed tomography (CT), magnetic resonance imaging (MRI), and/or nuclear)
* blood tests
* electrocardiogram (to measure the electrical activity of the heart)
* urine tests.
Participants will get PDS0101 injected under the skin every 4 weeks for 6 doses. Then they will get it every 3 months for 2 doses.
Participants will get M7824 (MSB0011395C) by intravenous infusion every 2 weeks. For this, a needle is inserted into a vein. The drug is given over a 1-hour period.
Participants will get NHS-IL12 injected under the skin every 4 weeks.
Participants will get the study drugs for up to 1 year. They will visit the NIH every 2 weeks. They will repeat the screening tests during the study.
About 28 days after treatment ends, participants will have a follow-up visit or telephone call. Then they will be contacted every 3 months for 1 year, and then every 6 months after that, for the rest of their life.
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...
Detailed 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 (MSB0011395C) (NCT02517398) 15 out of 43 (34.9%) participants with HPV associated malignancies had radiographic tumor responses according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or Immune Response Evaluation Criteria in Solid Tumors (iRECIST).
While the response rate observed with M7824 appears to be higher than single agent programmed cell death protein 1 (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 human papilloma virus (HPV) positive cancers (PDS0101), (2) a bifunctional fusion protein targeting programmed death-ligand 1 (PD-L1) and transforming growth factor (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.
Objective:
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 participant 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.
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 (MSB0011395C) (NCT02517398) 15 out of 43 (34.9%) participants with HPV associated malignancies had radiographic tumor responses according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or Immune Response Evaluation Criteria in Solid Tumors (iRECIST).
While the response rate observed with M7824 appears to be higher than single agent programmed cell death protein 1 (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 human papilloma virus (HPV) positive cancers (PDS0101), (2) a bifunctional fusion protein targeting programmed death-ligand 1 (PD-L1) and transforming growth factor (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.
Objective:
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 participant 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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 20-C-0045 | None | None | View |