AK117 (Anti-CD47) + Anti-EGFR for R/M HNSCC

NCT06508606 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 20241106
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

The administration of first-line pembrolizumab monotherapy or combined chemotherapy has been shown to improve survival among patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, over 80% of the patients still experience disease progression within a year. Upon progression, treatment options are notably constrained, typically comprising methotrexate, docetaxel, and cetuximab. The median progression-free survivaland overall survival following chemotherapy, targeted therapy, or their combination are dismally low, ranging from 2-3 months and 6-8 months, respectively. The clinical trials CheckMate 141 and KEYNOTE 040 have led to the approval of Nivolumab and Pembrolizumab as second-line treatments for R/M HNSCC. Nevertheless, the response rates to immune monotherapy are limited, ranging from 10% to 35%. Even after receiving standard second-line immunotherapy, over 80% of patients encounter disease progression within 6 months, and more than 60% succumb to the disease within a year. Therefore, there is a dearth of a standardized treatment for R/M HNSCC after the failure of first- or second-line PD-1 (L1) inhibitors and/or platinum-based therapy

Conditions

Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Number of patients with Adverse Events (AEs)

  Characterization of incidence, severity and abnormal clinically significant laboratory findings of AEs

  Up to approximately 1 years

• OS

  overall survival

  Up to approximately 1 years

Secondary Outcomes (4)

• ORR

  Up to approximately 1 years

• PFS

  Up to approximately 1 years

• DCR

  Up to approximately 1 years

• DoR

  Up to approximately 1 years

Study Arms (1)

anti-CD47 (AK117) + anti-EGFR

EXPERIMENTAL

Patients meeting the inclusion criteria were given AK117 45mg/kg (D1, IVGTT, Q3W) in combination with anti-EGFR (initial dose 400mg/m2, subsequent doses of 250mg/m2, D1, QW) maintained for one year or until progression or intolerable toxicity occurred

Drug: AK117; Drug: anti-EGFR

Interventions

AK117 DRUG

AK117: 45mg/kg (D1, IVGTT, Q3W maintained for one year or until progression or intolerable toxicity occurred

anti-CD47 (AK117) + anti-EGFR

anti-EGFR DRUG

anti-EGFR:initial dose 400mg/m2, subsequent doses of 250mg/m2, D1, QW) maintained for one year or until progression or intolerable toxicity occurred

anti-CD47 (AK117) + anti-EGFR

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically or cytologically confirmed R/M HNSCC (including oral, oropharyngeal, hypopharyngeal, and laryngeal sites); Recurrence that cannot be cured by local treatment, and previous treatment with PD-1 (L1) inhibitors and/or platinum-based chemotherapy has failed.
• At least one measurable lesion according to RECIST v1.1, excluding previously irradiated lesions unless clear progression occurred more than 3 months after the last radiotherapy;
• Known HPV p16 status of oropharyngeal cancer;
• Known PD-L1 expression status;
• ECOG performance status of 0-1;
• Expected survival ≥ 3 months;
• Adequate bone marrow function, defined as: Hb ≥ 9.0 g/dL (90 g/L); ANC ≥ 1,500/mcL (1.5 × 10\^9/L); PLT ≥ 100,000/mcL (100 × 10\^9/L) and no blood transfusion within 3 weeks or growth factor (G-CSF, EPO) therapy within 2 weeks prior to dosing;
• Adequate liver function, defined as: TBIL ≤ 1.5× upper limit of normal (ULN); If no liver metastases, AST and ALT ≤ 2.5× ULN; if liver metastases are present, AST or ALT ≤ 3.0× ULN; ALP ≤ 1.5× ULN; if liver metastases ≤ 2× ULN; Serum albumin ≥ 30g/L;
• Adequate coagulation function: INR or PT, APTT ≤ 1.5× ULN. Participants on anticoagulant therapy should have these laboratory indices closely monitored;
• Adequate renal function, defined as creatinine ≤ 1.5× ULN or Ccr ≥ 50 mL/min calculated using the Cockcroft-Gault formula corrected for body surface area;
• Baseline left ventricular ejection fraction (LVEF) ≥ 50% measured by multiple-gated acquisition (MUGA) or echocardiogram (ECHO);
• No severe organic heart disease or arrhythmias;
• Women of childbearing potential (aged 15-49 years) must have a negative pregnancy test within 7 days before starting treatment. Both male and female participants of reproductive potential must agree to use effective contraceptive measures during the study period and for 3 months after discontinuation of treatment;
• Voluntary signed informed consent by the study participant.

You may not qualify if:

• Participants who have received treatment with cetuximab in the first line.
• Grade ≥2 peripheral neuropathy (according to CTCAE 5.0).
• Anticipated need for surgery or any other form of systemic or local anti-tumor therapy during the study, including maintenance therapy or radiotherapy for head and neck squamous cell carcinoma (excluding palliative treatment for non-target lesions).
• Received systemic chemotherapy within 3 weeks prior to first administration of study drug, received small molecule targeted therapy within 2 weeks prior to first administration or within 5 half-lives (whichever is longer), received anti-tumor biologic therapy, large molecule targeted therapy or immunotherapy within 4 weeks prior to first administration, or underwent major surgery (excluding minor surgery within 2 weeks with complete recovery); received radiotherapy within 14 days prior to first administration of study drug (excluding central nervous system radiotherapy which requires a washout period of ≥28 days).
• Known active central nervous system metastases and/or carcinomatous meningitis. Participants with treated brain metastases may participate if stable, without progressive or new neurological deficits, seizures, evidence of increased intracranial pressure, vomiting, or headaches.
• Lesions that are superficially ulcerated or have broken through at baseline.
• Residual toxicity from prior anti-tumor therapy (excluding alopecia, fatigue, and grade 2 hypothyroidism) or clinically significant laboratory abnormalities \> grade 1 (CTCAE v5.0).
• Pulmonary embolism or deep vein thrombosis within 3 months prior to first administration of study drug.
• Known history of malignant tumors.
• Any severe or uncontrolled systemic disease, including poorly controlled hypertension, diabetes.
• History of active bleeding, coagulation disorder, or participants receiving coumarin anticoagulant therapy.
• Known active hepatitis B or hepatitis C. Active hepatitis B is defined as known HBsAg positive and HBV DNA ≥500 IU/mL.
• Concurrent severe, uncontrolled infections or known human immunodeficiency virus (HIV) (HIV antibody positive) infection, or diagnosis of acquired immune deficiency syndrome (AIDS); or poorly controlled autoimmune disease; or history of allogeneic tissue/organ transplant, stem cell or bone marrow transplant, or prior solid organ transplant.
• Active bacterial, viral, fungal, rickettsial, or parasitic infections requiring systemic anti-infective therapy (unless treated and resolved before administration of study drug).
• Received live virus vaccination within 30 days prior to first administration of study drug. Use of inactivated seasonal influenza vaccine or approved COVID-19 vaccine is allowed, with a washout period of \>1 week prior to first administration of study drug.

Sponsors & Collaborators

• West China Hospital: lead

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

dexamethasone-(C21-phosphoramide)-(anti-EGFR)

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

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

Model Details: A single-arm Phase II clinical trial

Study Record Dates

• First Submitted: July 12, 2024
• First Posted: July 18, 2024
• Study Start: August 1, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: July 19, 2024

Record last verified: 2024-07