LSTA1-P02

The goal of this clinical trial is to test a new drug plus standard treatment compared with standard treatment alone in patients with advanced head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, and cholangiocarcinoma. The main questions it aims to answer are: - is the new drug plus standard treatment safe and tolerable - is the new drug plus standard treatment more effective than standard treatment

Inclusion Criteria

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

- Life expectancy ≥ 3 months

- At least one measurable metastatic lesion as assessed by RECIST 1.1

- Adequate organ and marrow function

- Adequate contraception

- Patients with any of the following:

- Histologically confirmed recurrent or metastatic HNSCC that is unresectable or considered incurable by local therapies and that has progressed after first-line immunotherapy. The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. Patients may not have primary tumor sites of the skin, paranasal sinuses, or the nasopharynx (any histology).

- Histologically or cytologically confirmed locally advanced unresectable or metastatic ESCC. ESCC subjects have documented clinical or radiographic disease progression by RECIST 1.1 after first-line immunotherapy.

- Pathologically confirmed metastatic or unresectable cholangiocarcinoma or gallbladder carcinoma (GBC), with no prior systemic chemotherapy or targeted therapy or loco-regional therapy (including but not limited to transarterial chemoembolization, transarterial embolization, transarterial chemotherapy or transarterial radioembolization). Patients with recurrent disease more than 6 months after completion of adjuvant chemotherapy following curative resection are eligible.

Exclusion Criteria

- Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results, including but not limited to:

- Any major surgery or irradiation less than 4 weeks prior to baseline disease assessment

- Active infection (viral, fungal, or bacterial) requiring systemic therapy

- Known active hepatitis B virus, hepatitis C virus, or HIV infection

- Active tuberculosis as defined per local guidance

- History of allogeneic tissue/solid organ transplant

- Prior malignancy requiring active treatment within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast

- Clinically significant or symptomatic cardiovascular/cerebrovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) within 6 months before randomization

- Treatment in another interventional clinical study within the last 1 year

- History or clinical evidence of symptomatic central nervous system (CNS) metastases

- Has had prior targeted small molecule therapy, or radiation therapy for unresectable or metastatic HNSCC or ESCC

- For cholangiocarcinoma, active autoimmune disease that might deteriorate when receiving an immune-stimulatory agent. Patients with Type 1 diabetes, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.