Ignite Creation Date:
2024-05-06 @ 3:39 PM
Last Modification Date:
2024-10-26 @ 1:54 PM
Study NCT ID:
NCT04708470
Status:
RECRUITING
Last Update Posted:
2024-06-10
First Post:
2021-01-13
Brief Title:
A Phase III Study of Combination Immunotherapy for Advanced Cancers Including HPV-Associated Malignancies Small Bowel and Colon Cancers
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase III Study of Combination Immunotherapy for Advanced Cancers Including HPV-Associated Malignancies Small Bowel and Colon Cancers
Status:
RECRUITING
Status Verified Date:
2024-10-11
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
Often metastatic human papillomavirus HPV associated cancers cannot be cured They also do not respond well to treatment Some forms of colon cancer also have poor responses to treatment Researchers want to see if a new drug treatment can help people with these types of cancers
Objective
To find a safe dose of entinostat in combination with PDS01ADC and bintrafusp alfa and to see if this treatment will cause tumors to shrink
Eligibility
Adults ages 18 and older who have cervical oropharyngeal anal vulvar vaginal penile squamous cell rectal or another cancer that may be associated with HPV infection or microsatellite stable small bowel or colorectal cancer
Design
Participants will be screened with a medical history and physical exam Their ability to do daily activities will be assessed They may have imaging scans of the brain andor chest abdomen and pelvis They may have nuclear bone scans They will have an electrocardiogram to test heart function They will have blood and urine tests They may have a tumor biopsy Participants with skin lesions may have them photographed
Some screening tests will be repeated during the study
Treatment will be done in 28-day cycles Participants will get bintrafusp alfa through an intravenous catheter every 2 weeks They will get PDS01ADC as an injection under the skin every 4 weeks They will take entinostat by mouth once a week They will complete a medicine diary
Participants will get treatment for 2 years They will have 1-2 follow-up visits in the 30 days after treatment ends Then they will be contacted every 6 months to check on their health
Often metastatic human papillomavirus HPV associated cancers cannot be cured They also do not respond well to treatment Some forms of colon cancer also have poor responses to treatment Researchers want to see if a new drug treatment can help people with these types of cancers
Objective
To find a safe dose of entinostat in combination with PDS01ADC and bintrafusp alfa and to see if this treatment will cause tumors to shrink
Eligibility
Adults ages 18 and older who have cervical oropharyngeal anal vulvar vaginal penile squamous cell rectal or another cancer that may be associated with HPV infection or microsatellite stable small bowel or colorectal cancer
Design
Participants will be screened with a medical history and physical exam Their ability to do daily activities will be assessed They may have imaging scans of the brain andor chest abdomen and pelvis They may have nuclear bone scans They will have an electrocardiogram to test heart function They will have blood and urine tests They may have a tumor biopsy Participants with skin lesions may have them photographed
Some screening tests will be repeated during the study
Treatment will be done in 28-day cycles Participants will get bintrafusp alfa through an intravenous catheter every 2 weeks They will get PDS01ADC as an injection under the skin every 4 weeks They will take entinostat by mouth once a week They will complete a medicine diary
Participants will get treatment for 2 years They will have 1-2 follow-up visits in the 30 days after treatment ends Then they will be contacted every 6 months to check on their health
Detailed Description:
Background
Although PD-1L1 inhibitors have been approved for the treatment of over a dozen different tumor types in recent years the majority of patients with advanced cancer still do not respond to these agents including patients with microsatellite stable MSS colon cancer and patients with checkpoint refractory cancers eg oropharyngeal cervical
Clinical studies suggest that treatment with a bifunctional fusion protein targeting PD-L1 and TGF beta bintrafusp alfa may help overcome resistance or refractoriness to anti PD-1L1 therapy alone
Preclinical and clinical studies suggest that treatment with a histone deacetylase inhibitor HDAC inhibitor concomitantly with anti PD-1L1 therapy is safe and may help overcome resistance or refractoriness to anti PD-1L1 therapy alone
Preclinical and clinical studies suggest that treatment with a tumor targeted immunocytokine PDS01ADC concomitantly with anti PD-1L1 therapy is safe and may help overcome resistance or refractoriness to anti PD-1L1 therapy alone
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 an HDAC inhibitor entinostat 2 a tumor targeted immunocytokine PDS01ADC and 3 a bifunctional fusion protein targeting PD-L1 and TGF beta bintrafusp alfa produces greater anti-tumor activity than single or dual combinations of these agents
Objectives
Phase I To determine the recommended phase II dose RP2D of entinostat in combination with PDS01ADC and bintrafusp alfa
Phase II To evaluate the objective response rate ORR PRCR according to Response Evaluation Criteria RECIST 11 of the combination of entinostat NHS-IL12 and bintrafusp alfa in two separate populations
Checkpoint refractory human papillomavirus HPV associated malignancies
MSS small bowel or colorectal cancer
Eligibility
Age 18 years old
Phase I Subjects with cytologically or histologically confirmed locally advanced or metastatic HPV associated malignancies or MSS small bowel or colorectal cancer Cohort 1
Phase II Subjects with cytologically or histologically confirmed locally advanced or metastatic HPV associated malignancies Cohort 2 or MSS small bowel or colorectal cancer Cohort 3
Prior first line systemic therapy is required unless the participant declines standard treatment after appropriate counseling has been provided
Subjects must have measurable disease per RECIST 11
Design
This is a phase III trial of combination immunotherapy
Participants will be treated with a one week lead in of entinostat alone followed by the combination of entinostat PDS01ADC and bintrafusp alfa Arm 1 Arm 2 Up to 12 additional participants will be treated with a one week lead in of entinostat alone followed by the combination with PDS01ADC without bintrafusp alfa Arm 3
Phase I Arm 1
Arm 1 will be conducted using dose escalationde-escalation of entinostat and dose escalation of PDS01ADC with a fixed dose of bintrafusp alfa in Cohort 1 up to 36 total
Once the combination of all three agents has been determined to be safe participants from Cohort 2 and Cohort 3 may enroll into -Phase II
Phase II Arm 2 and Arm 3
Arm 2 will be conducted using a Simon optimal two-stage design
Cohort 2 checkpoint refractory HPV associated malignancies 16 total and cohort 3 MSS small bowel or colorectal cancer 16 total participants will each be enrolled to Arm 2
If one or more out of twelve participants in a given cohort 2 or 3 has an objective response accrual will be expanded to enroll 16 evaluable participants on that cohort
If 3 or more of 16 188 participants respond in a given cohort-arm combination that would be sufficiently interesting to warrant further study of the combination in later trials in that disease type
Arm 3 Up to 12 additional participants with checkpoint refractory HPV associated cancer may enroll to the combination of entinostat plus PDS01ADC without bintrafusp alfa
Although PD-1L1 inhibitors have been approved for the treatment of over a dozen different tumor types in recent years the majority of patients with advanced cancer still do not respond to these agents including patients with microsatellite stable MSS colon cancer and patients with checkpoint refractory cancers eg oropharyngeal cervical
Clinical studies suggest that treatment with a bifunctional fusion protein targeting PD-L1 and TGF beta bintrafusp alfa may help overcome resistance or refractoriness to anti PD-1L1 therapy alone
Preclinical and clinical studies suggest that treatment with a histone deacetylase inhibitor HDAC inhibitor concomitantly with anti PD-1L1 therapy is safe and may help overcome resistance or refractoriness to anti PD-1L1 therapy alone
Preclinical and clinical studies suggest that treatment with a tumor targeted immunocytokine PDS01ADC concomitantly with anti PD-1L1 therapy is safe and may help overcome resistance or refractoriness to anti PD-1L1 therapy alone
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 an HDAC inhibitor entinostat 2 a tumor targeted immunocytokine PDS01ADC and 3 a bifunctional fusion protein targeting PD-L1 and TGF beta bintrafusp alfa produces greater anti-tumor activity than single or dual combinations of these agents
Objectives
Phase I To determine the recommended phase II dose RP2D of entinostat in combination with PDS01ADC and bintrafusp alfa
Phase II To evaluate the objective response rate ORR PRCR according to Response Evaluation Criteria RECIST 11 of the combination of entinostat NHS-IL12 and bintrafusp alfa in two separate populations
Checkpoint refractory human papillomavirus HPV associated malignancies
MSS small bowel or colorectal cancer
Eligibility
Age 18 years old
Phase I Subjects with cytologically or histologically confirmed locally advanced or metastatic HPV associated malignancies or MSS small bowel or colorectal cancer Cohort 1
Phase II Subjects with cytologically or histologically confirmed locally advanced or metastatic HPV associated malignancies Cohort 2 or MSS small bowel or colorectal cancer Cohort 3
Prior first line systemic therapy is required unless the participant declines standard treatment after appropriate counseling has been provided
Subjects must have measurable disease per RECIST 11
Design
This is a phase III trial of combination immunotherapy
Participants will be treated with a one week lead in of entinostat alone followed by the combination of entinostat PDS01ADC and bintrafusp alfa Arm 1 Arm 2 Up to 12 additional participants will be treated with a one week lead in of entinostat alone followed by the combination with PDS01ADC without bintrafusp alfa Arm 3
Phase I Arm 1
Arm 1 will be conducted using dose escalationde-escalation of entinostat and dose escalation of PDS01ADC with a fixed dose of bintrafusp alfa in Cohort 1 up to 36 total
Once the combination of all three agents has been determined to be safe participants from Cohort 2 and Cohort 3 may enroll into -Phase II
Phase II Arm 2 and Arm 3
Arm 2 will be conducted using a Simon optimal two-stage design
Cohort 2 checkpoint refractory HPV associated malignancies 16 total and cohort 3 MSS small bowel or colorectal cancer 16 total participants will each be enrolled to Arm 2
If one or more out of twelve participants in a given cohort 2 or 3 has an objective response accrual will be expanded to enroll 16 evaluable participants on that cohort
If 3 or more of 16 188 participants respond in a given cohort-arm combination that would be sufficiently interesting to warrant further study of the combination in later trials in that disease type
Arm 3 Up to 12 additional participants with checkpoint refractory HPV associated cancer may enroll to the combination of entinostat plus PDS01ADC without bintrafusp alfa
Study Oversight
Has Oversight DMC:
None
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?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 21-C-0007 | None | None | None |