Official Title
A Phase II Study of AK117 (Anti-CD47) Combined With Anti-EGFR in the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Brief Summary

The administration of first-line pembrolizumab monotherapy or combined chemotherapy hasbeen shown to improve survival among patients with recurrent or metastatic head and necksquamous cell carcinoma (R/M HNSCC). However, over 80% of the patients still experiencedisease progression within a year. Upon progression, treatment options are notablyconstrained, typically comprising methotrexate, docetaxel, and cetuximab. The medianprogression-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 approvalof Nivolumab and Pembrolizumab as second-line treatments for R/M HNSCC. Nevertheless, theresponse rates to immune monotherapy are limited, ranging from 10% to 35%. Even afterreceiving standard second-line immunotherapy, over 80% of patients encounter diseaseprogression 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 failureof first- or second-line PD-1 (L1) inhibitors and/or platinum-based therapy

Detailed Description

Not Provided

Not yet recruiting
Head and Neck Squamous Cell Carcinoma

Drug: AK117

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

Drug: anti-EGFR

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

Eligibility Criteria

Inclusion Criteria:

1. 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.

2. 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;

3. Known HPV p16 status of oropharyngeal cancer;

4. Known PD-L1 expression status;

5. ECOG performance status of 0-1;

6. Expected survival ≥ 3 months;

7. 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;

8. 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;

9. Adequate coagulation function: INR or PT, APTT ≤ 1.5× ULN. Participants on
anticoagulant therapy should have these laboratory indices closely monitored;

10. 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;

11. Baseline left ventricular ejection fraction (LVEF) ≥ 50% measured by multiple-gated
acquisition (MUGA) or echocardiogram (ECHO);

12. No severe organic heart disease or arrhythmias;

13. 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;

14. Voluntary signed informed consent by the study participant.

Exclusion Criteria:

1. Participants who have received treatment with cetuximab in the first line.

2. Grade ≥2 peripheral neuropathy (according to CTCAE 5.0).

3. 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).

4. 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).

5. 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.

6. Lesions that are superficially ulcerated or have broken through at baseline.

7. Residual toxicity from prior anti-tumor therapy (excluding alopecia, fatigue, and
grade 2 hypothyroidism) or clinically significant laboratory abnormalities > grade 1
(CTCAE v5.0).

8. Pulmonary embolism or deep vein thrombosis within 3 months prior to first
administration of study drug.

9. Known history of malignant tumors.

10. Any severe or uncontrolled systemic disease, including poorly controlled
hypertension, diabetes.

11. History of active bleeding, coagulation disorder, or participants receiving coumarin
anticoagulant therapy.

12. Known active hepatitis B or hepatitis C. Active hepatitis B is defined as known
HBsAg positive and HBV DNA ≥500 IU/mL.

13. 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.

14. Active bacterial, viral, fungal, rickettsial, or parasitic infections requiring
systemic anti-infective therapy (unless treated and resolved before administration
of study drug).

15. 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.

16. History of or concurrent interstitial pneumonia, severe chronic obstructive
pulmonary disease with respiratory failure, severe pulmonary insufficiency,
symptomatic bronchospasm.

17. Received immunological therapy for any reason, including long-term use equivalent to
>10 mg/day prednisone within 7 days prior to first administration of study drug or
at any time during the study.

18. Uncontrolled pleural, peritoneal, pelvic effusion, or pericardial effusion requiring
drainage ≥1 time per month.

19. Pregnancy test positive or breastfeeding participants. Women and men participants
who do not plan to take adequate contraceptive measures within 180 days after the
end of treatment.

20. Any other disease or clinically significant laboratory parameter abnormalities,
severe medical or psychiatric condition, including substance abuse including alcohol
abuse, which the investigator believes may compromise the safety of the participant,
the integrity of the study, participant's ability to participate in the study, or
interfere with the study objectives and result analysis.

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: 75 Years
Locations

Not Provided

Not Provided

West China Hospital
NCT Number
MeSH Terms
Squamous Cell Carcinoma of Head and Neck
dexamethasone-(C21-phosphoramide)-(anti-EGFR)