Neoadjuvant Immunoradiotherapy With Evorpacept and Pembrolizumab in HPVOPC (Human Papilloma Virus Oropharynx Cancer)

Neoadjuvant Radiation and Evorpacept (ALX148) in Combination With Pembrolizumab In Patients With Previously Untreated Locally Advanced, Resectable, HPVOPC (Human Papilloma Virus Oropharynx Cancer)

The majority of head and neck cancer patients do not respond to immunotherapies, and clinical responses are often not durable. However, targeting tumors with stereotactic radiation in combination with immunotherapy while sparing draining lymphatics enhances anticancer immunity, resulting in dramatic response in HPV (Human Papilloma Virus) virus related cancers of the throat. This trial will leverage targeted tumor radiation and immunotherapy in advance of standard surgical therapy to improve the response of HPV (Human Papilloma Virus) throat cancer to radiation and immunotherapy.

Study Overview

• Status: Recruiting
• Conditions: Oropharynx Cancer
• Intervention / Treatment: Drug: Evorpacept

Detailed Description

This is a prospective, multi-center, open-label, one-arm, two-stage, Phase II study to evaluate the efficacy of neoadjuvant immunoradiotherapy (NIRT) in patients with stage I HPVOPC (Human Papilloma Virus Oropharynx Cancer) amenable to surgical resection, including AJCC (American Joint Committee on Cancer) VIII T1-2N1M0 HPVOPC (Human Papilloma Virus Oropharynx Cancer) and excluding patients with solitary lymph nodes less than 3 cm. A Simon's two-stage optimal design is used for this study. We will test the hypothesis that neoadjuvant stereotactic tumor targeting radiation along with CD47 inhibition (evorpacept) and PD-1 inhibition (pembrolizumab) provides pathologic response compared to current standard of care rates of locoregional control.

• Study Type: Interventional
• Enrollment (Estimated): 29
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Joseph A Califano, MD; Phone Number: 858-822-6197; Email: jcalifano@health.ucsd.edu

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • Recruiting
      • UC San Diego Moores Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of Stage I T1-2N1M0 HPVOPC (Human Papilloma Virus Oropharynx Cancer)
• Amenable to surgical resection
• Are able to safely receive neoadjuvant radiation and Evorpacept/Pembrolizumab

Exclusion Criteria:

• Patients with solitary lymph nodes less than 3 cm

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: Treatment; Stereotactic radiation therapy (SBRT (8GyX3)) will be delivered to gross tumor volume (GTV) +3mm, followed by Pembrolizumab 200 mg IV and Evorpacept 45 mg/kg IV every three weeks x 2 cycles followed by surgical resection of primary tumor and neck dissection.	Drug: Evorpacept; After stereotactic radiation to primary tumor and neck on week 1 of study, Evorpacept 45 mg/kg is administered by IV infusion every three weeks starting on Week 2, Day 1 of study for a total two 21-day cycles (6 weeks); Other Names: ALX 148

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic complete response	Pathologic response is determined when surgery is performed at week 7-10 of study	week 7-10
Major pathologic response	Major pathologic response is defined as <10% viable tumor cells in the resection specimen) after surgical resection	week 7-10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical response	clinical response will be determined by clinical and radiographic criteria by comparison of pretreatment and post-treatment assessment prior to surgery	week 7
clinical to pathologic down-staging	clinical to pathologic down-staging will be assessed by comparing pretreatment AJCC (American Joint Committee on Cancer) VIII stage to pathologic stage determined by surgical pathology results. And decrease in overall Stage or decrease in T or N category will be defined as down staging.	week 7-10
overall survival	survival will be determined based on intent to treat analysis at conclusion of study after 3 years	3 years
disease free survival	subjects will be assessed for presence of disease after completion of treatment and up to three years	3 years
Safety and toxicity	Safety and toxicity will be assessed by CTCAE for overall toxicity and safety and Clavien-Dindo for toxicity related to surgery.	11 months to three years
Patient-reported quality of life and functional outcomes (score 0-100 with 100 being best possible score)	The University of Washington-Quality of Life (UW-QOL) to assess standard penetration-aspiration score (PAS) will be used to assess patient and observer-reported quality of life and functional outcomes.	post treatment at 7, 11 weeks and at 3 and 12 months
Patient-reported quality of life and functional outcomes (score 20-100 with 100 being best possible score)	MD Anderson Dysphagia Inventory (MDADI) to assess standard penetration-aspiration score (PAS) will be used to assess patient and observer-reported quality of life and functional outcomes.	post treatment at 7, 11 weeks and at 3 and 12 months
Observer-reported quality of life and functional outcomes	Video Fluoroscopic Swallow Study (VFSS) to assess standard penetration-aspiration score (PAS) will be used to assess patient and observer-reported quality of life and functional outcomes.	post treatment at 7, 11 weeks and at 3 and 12 months
Immune Correlates (T-cell infiltration)	Patients will undergo assessment of T-cell infiltration into primary tumors expressed as % staining in primary tumor sections on immunohistochemical staining.	7-11 weeks
Immune Correlates (shared tumor and sentinel node T-cell clones)	Patients will undergo assessment of frequency of shared tumor and sentinel node T-cell clones as defined by absolute number of shared clones,	7-11 weeks
Immune Correlates (B-cell germinal centers)	Patients will undergo assessment of number of B-cell germinal centers in draining sentinel lymph nodes compared to non-sentinel nodes as defined by average number of B-cell germinal centers per high powered field with random sampling of at least 10 high powered fields on microscopy.	7-11 weeks

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Investigators: Principal Investigator: Jospeh A Califano, MD, University of California, San Diego

Publications and helpful links

General Publications

• Leidner R, Crittenden M, Young K, Xiao H, Wu Y, Couey MA, Patel AA, Cheng AC, Watters AL, Bifulco C, Morris G, Rushforth L, Nemeth S, Urba WJ, Gough M, Bell RB. Neoadjuvant immunoradiotherapy results in high rate of complete pathological response and clinical to pathological downstaging in locally advanced head and neck squamous cell carcinoma. J Immunother Cancer. 2021 May;9(5):e002485. doi: 10.1136/jitc-2021-002485.

Helpful Links

• This publication presents phase I data supporting a neoadjuvant immunoradiotherapy approach for HPVOPC (Human Papilloma Virus Oropharynx Cancer), demonstrating 90% pathologic complete response.

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2024
• Primary Completion (Estimated): August 20, 2026
• Study Completion (Estimated): May 30, 2028

Study Registration Dates

• First Submitted: February 28, 2023
• First Submitted That Met QC Criteria: March 14, 2023
• First Posted (Actual): March 28, 2023

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Neoplasms, Squamous Cell; Oropharyngeal Neoplasms; Papilloma
• Other Study ID Numbers: 806684

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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