NCT04708470

A Phase I/II Study of Combination Immunotherapy for Advanced Cancers Including HPV-Associated Malignancies, Small Bowel, and Colon Cancers

Active, enrolled Phase 1, PHASE2 Last updated 6 April 2026

What this trial tests

Phase 1, PHASE2 trial testing Bintrafusp Alfa in Oropharyngeal Cancer in 55 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

5 October 2021

Primary endpoint
30 November 2026

30 November 2026

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 1, PHASE2
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	55
Start date	5 October 2021
Primary completion	30 November 2026
Estimated completion	30 November 2026
Sites	1 location across United States

Drugs / interventions tested

• Bintrafusp Alfa — full drug profile →
• PDS01ADC — full drug profile →
• Entinostat — full drug profile →

Conditions studied

• Oropharyngeal Cancer — all drugs for Oropharyngeal Cancer →
• Neck Cancer — all drugs for Neck Cancer →
• Human Papillomavirus — all drugs for Human Papillomavirus →
• HPV — all drugs for HPV →

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 18 to 120, any sex, with Oropharyngeal Cancer or Neck Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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 and/or 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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Combination strategies with PD-1/PD-L1 blockade: current advances and future directions.
   Yi M, Zheng X, Niu M, Zhu S, et al · · 2022 · cited 1018× · PMID 35062949 · DOI 10.1186/s12943-021-01489-2
2. Targeting TGF-β signal transduction for fibrosis and cancer therapy.
   Peng D, Fu M, Wang M, Wei Y, et al · · 2022 · cited 752× · PMID 35461253 · DOI 10.1186/s12943-022-01569-x
3. TGF-β signaling in health, disease, and therapeutics.
   Deng Z, Fan T, Xiao C, Tian H, et al · · 2024 · cited 737× · PMID 38514615 · DOI 10.1038/s41392-024-01764-w
4. Intratumoural administration and tumour tissue targeting of cancer immunotherapies.
   Melero I, Castanon E, Alvarez M, Champiat S, et al · · 2021 · cited 358× · PMID 34006998 · DOI 10.1038/s41571-021-00507-y
5. Targeting cytokine and chemokine signaling pathways for cancer therapy.
   Yi M, Li T, Niu M, Zhang H, et al · · 2024 · cited 264× · PMID 39034318 · DOI 10.1038/s41392-024-01868-3
6. Epigenetics-targeted drugs: current paradigms and future challenges.
   Dai W, Qiao X, Fang Y, Guo R, et al · · 2024 · cited 131× · PMID 39592582 · DOI 10.1038/s41392-024-02039-0
7. Emerging strategies in targeting tumor-resident myeloid cells for cancer immunotherapy.
   Wang Y, Johnson KCC, Gatti-Mays ME, Li Z. · · 2022 · cited 103× · PMID 36031601 · DOI 10.1186/s13045-022-01335-y
8. TGF-beta signal transduction: biology, function and therapy for diseases.
   Tie Y, Tang F, Peng D, Zhang Y, et al · · 2022 · cited 97× · PMID 36534225 · DOI 10.1186/s43556-022-00109-9