The Efficacy and Safety of Pucotenlimab (PD-1) Combined With Becotatugvedotin (EGFR-ADC) in Advanced Cholangiocarcinoma

The Efficacy and Safety of Pucotenlimab (PD-1) Combined With Becotatugvedotin (EGFR-ADC) in Advanced Cholangiocarcinoma

(1) Primary efficacy endpoint: Objective Response Rate (ORR) after 2 treatment cycles. ORR is defined as the proportion of subjects with complete response (CR) and partial response (PR) among all subjects. (2) Secondary efficacy endpoints include Progression-Free Survival (PFS), 2-year Relapse-Free Survival Rate, Disease Control Rate (DCR), Duration of Response (DOR), Adverse Reaction Incidence, 1-year Overall Survival Rate, 2-year Overall Survival Rate. Safety assessment includes physical examination, physical condition assessment (based on ECOG score), clinical laboratory tests and concomitant medication status. All observed drug toxicities and side effects need to be classified according to NCICTCAE and evaluated for their correlation with the drug. Patient Quality of Life (QoL) assessment uses the EORTC QLQC30 questionnaire and the BIL21 questionnaire. Recurrence patterns are classified as local recurrence and distant recurrence. Local control status is defined as the local failure rate (occurrence of local recurrence or local lymph node metastasis).

Inclusion Criteria:

• 1) Age ≥ 18 years old, both male and female are acceptable. 2) Histologically confirmed unresectable or metastatic cholangiocarcinoma (including: gallbladder cancer, intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma), or (including: gallbladder cancer, intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma, after previous chemotherapy failure); 3) ECOG PS score 0-1. 4) Normal major organ functions, without severe blood, heart, lung, liver, kidney, bone marrow, or immune deficiency diseases.

  5) For female subjects of childbearing age, a pregnancy test (serum/urine) result must be negative within 14 days before enrollment, and they must voluntarily use appropriate methods of contraception during the observation period and 8 weeks after the last administration of the study drug; for male subjects, surgical sterilization or consent to use appropriate methods of contraception during the observation period and 8 weeks after the last administration of the study drug is required.

  6) IHC test is positive for EGFR. 7) Expected good compliance and able to follow up on efficacy and adverse reactions as per the protocol.

  8) Voluntary participation in this study and signing the informed consent form. If the subject is unable to read and sign the informed consent form due to lack of capacity, the guardian should act on behalf of the informed process and sign the informed consent form. If the subject is unable to read the informed consent form (such as illiterate subjects), a witness should witness the informed process and sign the informed consent form.

Exclusion Criteria:

• 1) Received PD1, PDL1, PDL2, CTLA4 treatment before enrollment, or directly received another stimulating or co-inhibitory T cell receptor (such as CTLA-4, OX40, CD137) treatment.

  2) Used any other study drug within 4 weeks before enrollment. 3) Has any active autoimmune disease or autoimmune disease history (such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitaryitis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (after hormone replacement therapy can be included)); has completely resolved childhood asthma and no need for any intervention after adulthood, and can be included, but patients requiring medical intervention with bronchodilators are not included.

  4) Has congenital or acquired immune dysfunction, such as human immunodeficiency virus (HIV) infection.

  5) Has uncontrolled clinical symptoms or diseases of the heart, such as NYHA II or above heart failure, unstable angina pectoris, heart attack within 1 year, patients with clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention.

  6) Had severe infection within 4 weeks before the first administration (such as requiring intravenous infusion of antibiotics, antifungal or antiviral drugs), or had unexplained fever > 38.5℃ during screening or before the first administration.

  7) Has a history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.

  8) Had a live attenuated vaccine administered within 4 weeks before the first administration or is planned to be administered during the study period.

  9) Had other systemic malignant tumors within the last 5 years (excluding cured skin basal cell carcinoma and cervical carcinoma in situ and ovarian cancer).

  10) Has known allergies to any study drug. 11) Pregnant or lactating women, subjects with reproductive capacity who are unwilling to take effective contraceptive measures.

  12) Vulnerable groups other than the elderly or illiterate, including those with mental illness, cognitive impairment, critically ill patients, etc.

  13) Other situations considered by the investigator as not suitable for inclusion in this study. Such as: the patient already has central nervous system metastasis. There are serious laboratory test abnormalities, accompanied by factors related to family or society, which may affect the safety of the subjects or the collection of data/samples.