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

Oropharynx Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05787639
• Other study ID #: 806684
• Status: Recruiting
• Phase: Phase 2
• Start date: February 20, 2024
• Est. completion date: May 30, 2028

Study information

• Verified date: February 2024
• Source: University of California, San Diego
• Contact: Joseph A Califano, MD
• Phone: 858-822-6197
• Email: jcalifano[@]health.ucsd.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 29
• Est. completion date: May 30, 2028
• Est. primary completion date: August 20, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Oropharyngeal Neoplasms
• Oropharynx Cancer
• Papilloma

Intervention

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)

Locations

Country	Name	City	State
United States	UC San Diego Moores Cancer Center	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Diego

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 clin — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic complete response	Pathologic response is determined when surgery is performed at week 7-10 of study	week 7-10
Primary	Major pathologic response	Major pathologic response is defined as <10% viable tumor cells in the resection specimen) after surgical resection	week 7-10
Secondary	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
Secondary	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
Secondary	overall survival	survival will be determined based on intent to treat analysis at conclusion of study after 3 years	3 years
Secondary	disease free survival	subjects will be assessed for presence of disease after completion of treatment and up to three years	3 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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