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

NCT05787639 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 806684
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Oropharynx Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (11)

• clinical response

  week 7

• clinical to pathologic down-staging

  week 7-10

• overall survival

  3 years

• disease free survival

  3 years

• Safety and toxicity

  11 months to three years

Study Arms (1)

Treatment

EXPERIMENTAL

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

Interventions

Evorpacept DRUG

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)

Also known as: ALX 148

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Patients with solitary lymph nodes less than 3 cm

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (3)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

RECRUITING

Providence Health & Services

Portland, Oregon, 97213, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

Related Publications (1)

• Mombelli A. [Periodontal diagnosis. The role of microbiology]. Schweiz Monatsschr Zahnmed. 1994;104(1):48-57. No abstract available. French, German.

  PMID: 8108690 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Oropharyngeal Neoplasms

Interventions

ALX148

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Study Officials

• Jospeh A Califano, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joseph A Califano, MD

CONTACT

858-822-6197; jcalifano@health.ucsd.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Otolaryngology-Head and Neck Surgery

Model Details: A phase II clinical trial for AJCC (American Joint Committee on Cancer) VIII Stage I T1-2N1M0 HPVOPC, including patients amenable to surgical resection, excluding patients with solitary lymph nodes less than 3 cm who are amenable to surgical therapy alone. 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. The primary endpoint is pathologic response compared to historical standard of care rates of locoregional control, and secondary endpoints are clinical response, survival, and safety and toxicity.

Study Record Dates

• First Submitted: February 28, 2023
• First Posted: March 28, 2023
• Study Start: February 20, 2024
• Primary Completion (Estimated): August 20, 2026
• Study Completion (Estimated): May 30, 2028
• Last Updated: June 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)