A Phase II Study to Evaluate the Efficacy and Safety of SKB571 in Recurrent or Metastatic HNSCC Participants

• SKB571 (Drug): q3w
• Pembrolizumab (Drug): Pembrolizumab will be administered by intravenous infusion at a dose of 200 mg on Day 1 of each 3-week cycle, for a maximum treatment duration of 35 cycles (approximately 24 months).
• carboplatin (Drug): Carboplatin will be administered by intravenous infusion at a dose of AUC 5 mg/mL/min on Day 1 of each 3-week cycle (maximum dose of carboplatin not to exceed 750 mg), for a maximum of 6 cycles.
• Cisplatin (Drug): Cisplatin will be administered by intravenous infusion at a dose of 75 mg/m2 on Day 1 of each 3-week cycle, for a maximum of 6 cycles.

Primary outcomes

• Objective response rate (ORR) of SKB571 [Up to approximately 24 months.]: ORR as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Secondary outcomes

• Progression-free survival (PFS) [Up to approximately 24 months.]: Time from start of treatment to progression of disease (PD) or death, whichever occurs first, in patients with tumors.
• Duration of Response (DOR) [Up to 24 months]: Time from the start of the first assessment of CR or PR in tumor patients to PD or death due to any reason.
• Disease control rate (DCR) [Up to 24 months]: Assessed by the investigators as per RECIST v1.1
• Overall Survival (OS) [Up to 24 months]: Time from start of treatment to death due to any reason.
• Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment [Up to approximately 24 months.]: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) (based on CTCAE v6.0), clinically significant abnormal laboratory test results.
• Maximum Plasma Concentration (Cmax) of SKB571-ADC [Up to approximately 24 months.]: Blood Samples will be collected to determine the Cmax of SKB571-ADC in the plasma.
• Minimum Plasma Concentration(Cmin) of SKB571-ADC [Up to approximately 24 months]: Blood samples will be collected to determine the Cmin of SKB571-ADC in the plasma.
• Maximum Plasma Concentration(Cmax) of SKB571-TAb [Up to approximately 24 months]: Blood samples will be collected to determine the Cmax of SKB571-TAb in the plasma.
• Minimum Plasma Concentration(Cmin) of SKB571-TAb [Up to approximately 24 months]: Blood samples will be collected to determine the Cmin of SKB571-TAb in the plasma.
• Maximum Plasma Concentration (Cmax) of unconjugated KL610348 [Up to approximately 24 months]: Blood Samples will be collected to determine the Cmax of unconjugated KL610348 in the plasma.
• Minimum Plasma Concentration(Cmin) of unconjugated KL610348 [Up to approximately 24 months]: Blood Samples will be collected to determine the Cmin of unconjugated KL610348 in the plasma.
• Immunogenicity of SKB571 [Up to approximately 24 months.]: Incidence of anti-drug antibody (ADA) against SKB571.

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* Age ≥ 18 and ≤ 75 years at the time of signing the informed consent form.
* Histologically or cytologically confirmed recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that is not curable by local therapy and not amenable to curative surgery, with the primary tumor located in the oral cavity, oropharynx, hypopharynx, or larynx.
* Subjects with at least one measurable lesion assessed by the investigator according to RECIST v1.1.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 7 days before the first dose.
* Participants who have adequate bone marrow, liver, kidney, and coagulation function.
* Male and female participants must agree to use highly effective methods of contraception during the specified period of the study.
* Participants must voluntarily join this study, sign the informed consent form (ICF), and be able to comply with the visits and related procedures specified in the protocol.

Exclusion Criteria:

* History or current metastases to central nervous system.
* Subjects with other malignant tumors within 3 years prior to the first dose.
* Presence of any cardiovascular and cerebrovascular disorders or risk factors.
* Presence of uncontrolled systemic disease.
* Presence of clinically symptomatic or uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
* History of interstitial lung disease (ILD) or non-infectious pneumonitis.
* Presence within 3 months before the first dose of other moderate to severe lung disorders.
* Tumor invasion or compression of surrounding vital organs and major blood vessels.
* Unresolved toxicity from prior anti-tumor therapy.
* Serious infection within 4 weeks before the first dose.
* Presence of active HIV, hepatitis B or hepatitis C or co-infection with HBV and HCV.
* Known active pulmonary tuberculosis.
* Known history of allogeneic organ transplant or hematopoietic stem cell transplant.
* History of allergy to any component of the study drug or severe hypersensitivity to other monoclonal antibodies.
* Participants who have undergone major surgery or had severe trauma within 4 weeks before the first dose, or are expected to require major surgery during the study.
* Participants who have received other investigational drug treatments within 4 weeks before the first dose.
* Prior vaccination with a therapeutic anti-tumor vaccine, or any live vaccine within 4 weeks before the first dose, or planned vaccination with a live vaccine during the study.
* Participants who received systemic corticosteroid therapy with >10 mg/day of prednisone or other immunosuppressive drugs within 2 weeks before the first dose.
* Received strong inhibitors or strong inducers of cytochrome P450 (CYP3A4) or breast cancer resistance protein (BCRP) inhibitors within 2 weeks prior to the first dose or within 5 half-lives of the known drug (whichever is longer).
* Pregnant or breastfeeding women.
* Known history of psychosis or drug abuse that prevents the participant from cooperating with the study.
* Have local or systemic diseases caused by non-malignant tumors, or diseases or symptoms secondary to tumors, which may lead to higher medical risk and/or uncertainty in survival assessment, or may affect protocol compliance.
* Any condition that, in the investigator's opinion, interferes with the evaluation of the investigational product, participant safety, or interpretation of study results, or any other condition that the investigator deems unsuitable for participation in this study.

• Xin Li, Study director, Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.