BALSTILIMAB on Viral Clearance in HPV+ Oropharyngeal Cancer Patients

A Phase 2 Study to Assess the Effect of BALSTILIMAB (AGEN2034) on Viral Clearance in HPV-positive Oropharyngeal Cancer Patients With Persistent HPV Detection in Plasma cfDNA After Definitive Therapy

This study aims to leverage this unique property of HPV+ OPC to detect possible minimal residual disease represented by persistent viral detection after the completion of definitive treatment. The study will offer adjuvant immune therapy to patients with persistent viral detection and evaluate the clearance of viral load. It will evaluate the rate of viral clearance with immune therapy and establish the link between viral clearance and long-term disease control.

Study Overview

• Status: Withdrawn
• Conditions: Oropharyngeal Cancer; HPV
• Intervention / Treatment: Drug: Balstilimab

Detailed Description

Objectives:

Primary Objective:

To assess whether anti-PD1 will lead to the clearance of the virus in the plasma cfDNA in HPV+ OPC patients with persistent cfDNA HPV following definitive therapy

Secondary Objectives:

• One-year recurrence-free survival (1-yr RFS),
• 2-year RFS (2-yr RFS),
• Overall survival (2-yr OS),
• Safety and tolerability
• Compliance
• Quality of life (EORTC C30 will be utilized)

Correlative/Exploratory Objectives:

• Time to viral clearance in the oral rinse and plasma cfDNA with anti-PD1 treatment
• The concordance between plasma HPV and oral rinse HPV at diagnosis, post-definitive treatment and during adjuvant treatment
• The correlation between tumor mutations and persistence of HPV in oral rinse/cfDNA.
• The correlation between recurrence site (loco-regional vs. distant metastasis) and oral rinse vs. plasma HPV detection

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Subject must meet all of the following applicable inclusion criteria to participate in this study:

1. Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
2. Histologically or cytologically confirmed squamous cell carcinoma from oropharynx. note: patients with a clinical diagnosis of oropharyngeal cancer, awaiting a biopsy is eligible to consent for prescreening.
3. Stage I-III per AJCC 8th edition
4. Positive p16 immunohistochemistry or HPV testing, or p16/HPV status unknown with patients having a less than 10 pack-year smoking history
5. Age ≥ 18 years at the time of consent.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 for patients who receive treatment
7. Persistent detection of cfDNA HPV (≥ 16 copies/mL) in the absence of clinically evident disease at 3, 6, or 9 months following definitive treatment (surgery, systemic therapy, and/or radiation therapy).

8. Patients must have adequate hematologic, coagulation, hepatic, and renal function for anti-PD1 treatment. this includes:

   • ANC >/= 1,500/mm3
   • platelet count >/=100,000/mm3
   • HgB ≥ 9 g/dL (may be with transfusion)
   • Creatinine ≤ 1.5x ULN or creatinine clearance (measured via 24-hour urine collection) ≥40 mL/minute (that is, if serum creatinine is >1.5 times the ULN, a 24-hour urine collection to calculate creatinine clearance must be performed).
   • Total Serum Bilirubin ≤ 1.5 x ULN (Patients with known Gilbert Syndrome, a total bilirubin ≤ 3.0 x ULN, with direct bilirubin ≤ 1.5 x ULN)
   • SGOT, SGPT ≤ 3 X ULN
   • SGOT, SGPT ≤ 5 X ULN
9. Females of childbearing potential must not be breast feeding and must have a negative pregnancy test during screening and 7 days prior to initiation of study treatment. The patient must agree to use adequate contraception. Note: women will be considered post-menopausal if they have been amenorrheic for the past 12 months without an alternative medical cause. The following agespecific requirements must also apply: women < 50 years old: they would be considered postmenopausal if they have been amenorrheic for the past 12 months or more following cessation of exogenous hormonal treatments. The levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) must also be in the post-menopausal range (as per the institution). Women ≥ 50 years old: they would be considered post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of all exogenous hormonal treatments, or have had radiation-induced oophorectomy with the last menses > 1 year ago, or have had chemotherapyinduced menopause with >1 year interval since last menses, or have had surgical sterilization by either bilateral oophorectomy or hysterectomy.
10. Non-sterilized males who are sexually active with a female partner of childbearing potential must use adequate contraception for the duration of the study.

Exclusion Criteria:

Subjects should not enter the study if any of the following exclusion criteria are fulfilled:

1. Prior treatment history with anti-PD-1 or anti-PD-L1 therapies are not allowed.

2. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol, or active and uncontrolled infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).

   Screening for chronic conditions is not required.

3. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirement.
4. Active rheumatological or autoimmune conditions requiring systemic treatment, such as steroids.
5. Any evidence of current interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or noninfectious pneumonitis requiring high-dose glucocorticoids.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Balstilimab; Participants will receive Balstilimab by vein over about 30 minutes on Days 1 and 15 of each cycle (every 2 weeks)	Drug: Balstilimab; Given by Vein (IV); Other Names: Balstilimab IB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To establish the Overall survival.	through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: Agenus Inc.
• Investigators: Principal Investigator: Luana Guimaraes De Sousa, MD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• M D Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2023
• Primary Completion (Actual): May 4, 2026
• Study Completion (Actual): May 4, 2026

Study Registration Dates

• First Submitted: April 26, 2022
• First Submitted That Met QC Criteria: May 2, 2022
• First Posted (Actual): May 6, 2022

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Oropharyngeal Neoplasms; balstilimab
• Other Study ID Numbers: 2021-1077; NCI-2022-03805 (Other Identifier: NCI-CTRP-Clinical Trial Reporting Registry)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No