A Phase I/II Trial of HCB101 in Combination With Pembrolizumab for Patients With Platinum-Refractory, Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (SirH&N Trial)

Exclusion Criteria

• •* 1\. Medical Conditions:
• •* a) With a known history of hypersensitivity to any components of the study intervention.
• •* b) Subjects who have other malignancies requiring treatment within 2 years prior to the first dose of study intervention will be excluded, except for radically treated locally curable basal or squamous cell skin cancer and other malignancies that have been treated with no relapse within 2 years.
• •* c) Primary tumor in the central nervous system (CNS), or active or untreated CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate, provided they are clinically stable for at least 28 days and have no evidence of new or enlarging brain metastases and no requirements for high-dose corticosteroids 14 days prior to dosing with study intervention. Subjects on low-dose corticosteroids (\<20 mg prednisolone or equivalent per day) may participate.
• •* d) Clinically significant cardiovascular condition, including 1)History of congestive heart failure (New York Heart Association Class \>2), with only heart failure with preserved ejection fraction (HFpEF) included; 2)History of unstable angina within 6 months prior to the first dose of study intervention; 3)New-onset angina or myocardial infarction within 6 months prior to the first dose of study intervention; 4)New-onset of atrial fibrillation, supraventricular arrhythmia, or ventricular arrhythmia within 6 months prior to the first dose of study intervention and still in unstable condition and requiring treatment or intervention. History of atrial fibrillation, supraventricular arrhythmia, or ventricular arrhythmia will be allowed, provided the condition is stably controlled.
• •* e) History or presence of an abnormal ECG that, in the Investigator's opinion, is clinically meaningful (including QT interval corrected for heart rate using Fridericia's correction \[QTcF\] \>470 msec at Screening, pacemaker installation, or previous diagnosis of congenital long QT syndrome).
• •* f) Any previous treatment-related toxicities which have not recovered to ≤ Grade 1 as evaluated by National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 or baseline, except alopecia and anemia (Note: subjects with chronic Grade 2 toxicities which are well managed and stable may be eligible per the discretion of the Investigator, Grade 2 chemotherapy-induced neuropathy.)
• •* g) With known inherited or acquired bleeding disorders or bleeding diathesis.
• •* h) With a previously documented diagnosis of hemolytic anemia or Evans Syndrome in the last 3 months.
• •* i) With active autoimmune diseases that required systemic treatment (e.g., disease-modifying agents, corticosteroids, or immunosuppressants) within the past two years are excluded. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroids for adrenal or pituitary insufficiency) is allowed.
• •* j) With a history of or current non-infectious pneumonitis.
• •* k) With a history of severe hypersensitivity to monoclonal antibodies.
• •* 2\. Prior/Concomitant Therapy/Treatment
• •* a) Subjects who have undergone major surgery or radical radiotherapy within 28 days prior to the first dose of study intervention.
• •* b) Subjects who have undergone any investigational or approved systemic cancer therapy (including chemotherapy, immunotherapy, hormonal therapy, and herbal/alternative therapies with anti-cancer indications or targeted therapy) within 14 days or 5 half lives, whichever is longer, prior to the first dose of the study intervention.
• •* c) Subjects who have used herbal medication within 14 days prior to the first dose of the study intervention.
• •* d) Subjects who are active using of vitamin K antagonist anticoagulant like warfarin. Use of low molecular weight heparin and factor Xa inhibitors will be permitted on a case-by-case basis. There will be no restriction for daily aspirin ≤ 100 mg/QD.
• •* e) Subjects who have received any treatment targeting the CD47 or SIRPα pathway.
• •* f) Subjects who have previously received pembrolizumab treatment.
• •* g) Subjects who have received a live vaccine within 30 days prior to pembrolizumab administration.
• •* h) Subjects diagnosed with immunodeficiency, receiving systemic steroid therapy, or having received any other form of immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab.
• •* 3\. Participation in another clinical study with an investigational product administered in the last 14 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study intervention. An investigational device was used within 28 days prior to the first dose of study intervention.
• •* 4\. Reproductive and breastfeeding
• •* a) Women of reproductive potential who are unable to use effective contraception during treatment and for 4 months after the last dose.
• •* b) Women who are breastfeeding during treatment and for 4 months after the last dose.
• •* 5\. Infections:
• •* a) An uncontrolled acute infection, an active infection requiring systemic treatment, or subjects who have received systemic antibiotics within 7 days prior to the first dose of the study intervention (Note: prophylaxis use of systemic antibiotics treatment for upper tract infection is allowed as long as there is no violation of the requirement of concomitant medications).
• •* b) Known history of human immunodeficiency virus (HIV) infection.
• •* c) Active tuberculosis.
• •* d) Known history of hepatitis B or hepatitis C infection. Subjects who test positive for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody.
• •* 6\. Any other medical (e.g., Child-Pugh class B or C, pulmonary, metabolic, congenital, endocrinal or CNS disease, etc.), psychiatric, or social condition deemed by the Investigator to be likely to interfere with a subject's rights, safety, welfare or ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.