NCT06159621

CD40 Agonist and PD-1 Inhibitor in HNSCC

Neoadjuvant/Phase 1 Study of CD40 Agonist (LVGN7409) and PD-1 Inhibitor (LVGN3616) in Patients With Resectable HPV-negative Mucosal Head/Neck Squamous Cell Carcinoma (HNSCC)

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (actual)
• Sponsor: University of Pennsylvania · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Prospective, open-label, phase 1 study of CD40 agonist (LVGN7409) and PD-1 inhibition (LVGN3616 or nivolumab) in patients with resectable Human Papillomavirus (HPV)-negative mucosal head/neck squamous cell carcinoma (HNSCC). This protocol proposes to study the safety and immunological effects of LVGN7409, a CD40 agonistic antibody, when administered in combination with PD-1 inhibition prior to surgical resection.

Detailed description

This will be a prospective, open-label, window of opportunity study of LVGN7409 and LVGN3616 (or nivolumab) in resectable HPV-negative HNSCC with co-primary endpoints of safety and T cell infiltration, and secondary endpoint of anti-tumor efficacy. Doses of LVGN7409 and LVGN3616 (or nivolumab) are based on safety experience in prior and ongoing clinical trials. Dose escalation will not be conducted in this trial. The study is divided into the following treatment cohorts: I. Arm A: PD1 \[LVGN3616 (300mg) or nivolumab (240mg)\] II. Arm B: PD1 \[LVGN3616 (300mg) or nivolumab (240mg)\] + CD40 \[LVGN7409 (1mg/kg)\] Pre-Surgery and Surgery 1. Patients with potentially resectable HPV-negative HNSCC will be identified by H\&N surgeons and study coordinator (clinic screening). Consent and enrollment will take place in H\&N Surgery clinic by study investigators and/or the study coordinator. 2. Patients will need baseline non-Fine needle aspirate (FNA) tumor biopsy, either during standard of care exam under anesthesia (EUA) or via ultrasound-guided needle biopsy (prior archival non-FNA biopsy is acceptable as long as obtained within 6 months of screening). 3. Patients will be assigned in an alternating fashion to Arm A (PD1) or Arm B (PD1+CD40). At a separate infusion visit after enrollment, patients in arm A or arm B will receive a single administration of LVGN3616 (or nivolumab) or LVGN3616 (or nivolumab) and LVGN7409, respectively. In case of patient drop-out after screening/consent and before drug administration, that slot will be assigned to the next available patient. 4. Patients will be included in the primary endpoint calculations (safety) if they receive study drug. However, any patients unable to undergo planned surgery within 6 weeks will not contribute to the post-treatment immunologic sample analysis and this slot will be filled by a subsequent patient in order to achieve the goal of 10 paired samples in each arm. The maximum number of patients that can be replaced is 5. 5. After \~2 weeks (allowable range 6-42 days), patients will undergo planned surgical resection. Repeat imaging is not required. 6. Blood collection will occur on the day of drug administration prior to administration, 24-48 hours after administration, 1 week (+/-1 day) after administration, and on day of planned surgery. In person blood draws (D1, D7, etc.) can be waived in cases of transportation or logistical burden to the patient, at the discretion of the investigator. Post-Surgery 1. Guideline-based standard of care post-surgical adjuvant therapies, as indicated based on pathological features on surgical resection, will occur as part of routine clinical care. 2. Post-operative visits will occur every 3 months (+/-4 weeks) after surgery up to 1 year, which will serve as End of trial (EOT) visit and final Adverse Event (AE) assessment. The following will be performed during each of these visits: 1. Physical exam 2. Laboratory monitoring 3. AE assessment 4. Concomitant medication review

Conditions

• Head and Neck Squamous Cell Carcinoma

Interventions

Type	Name	Description
DRUG	PD-1inhibitor - LVGN 3616	Administration of one dose of LVGN 3616 - 300mg. Commercially available PD-1 inhibitor may be substituted.
DRUG	CD 40 Agonist - LVGN 7409	Administration of one dose of LVGN 7409 - 1mg/kg

Timeline

• Start date: 2024-07-02
• Primary completion: 2028-03-01
• Completion: 2028-03-01
• First posted: 2023-12-07
• Last updated: 2025-12-03

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study