Clinical trial NCT05787639: Neoadjuvant Immunoradiotherapy With Evorpacept and Pembrolizumab in HPVOPC (Human Papilloma Virus Oropharynx Cancer)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Oropharynx Cancer
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
First posted: 2023-03-28
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pathologic complete response
timeFrame: week 7-10
measure: Major pathologic response
timeFrame: week 7-10
Secondary outcomes:
measure: clinical response
timeFrame: week 7
measure: clinical to pathologic down-staging
timeFrame: week 7-10
measure: overall survival
timeFrame: 3 years
measure: disease free survival
timeFrame: 3 years
measure: Safety and toxicity
timeFrame: 11 months to three years
measure: Patient-reported quality of life and functional outcomes (score 0-100 with 100 being best possible score)
timeFrame: post treatment at 7, 11 weeks and at 3 and 12 months
measure: Patient-reported quality of life and functional outcomes (score 20-100 with 100 being best possible score)
timeFrame: post treatment at 7, 11 weeks and at 3 and 12 months
measure: Observer-reported quality of life and functional outcomes
timeFrame: post treatment at 7, 11 weeks and at 3 and 12 months
measure: Immune Correlates (T-cell infiltration)
timeFrame: 7-11 weeks
measure: Immune Correlates (shared tumor and sentinel node T-cell clones)
timeFrame: 7-11 weeks
measure: Immune Correlates (B-cell germinal centers)
timeFrame: 7-11 weeks
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Portland
country: United States
facility: Providence Health & Services
state: Oregon
Study officials:
affiliation: University of California, San Diego
name: Jospeh A Califano, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.