================================================================================ BIOVANCE THERAPEUTICS — CLINICAL PROTOCOL AMENDMENT AUDIT PACK STUDY IDENTIFIER: BV-402 (PHASE II ADVANCED SOLID TUMORS) FOR TESTING OFFLINE / HIPAA & IRB COMPLIANCE WORKFLOWS ================================================================================ NOTICE: This is a fictional protocol document prepared strictly for document-AI, regulatory compliance, and evidence-verification testing. All drug candidates, dosage schedules, criteria thresholds, and trial outcomes are entirely synthetic. ================================================================================ ================================================================================ RECORD 1: CLINICAL STUDY PROTOCOL — PROTOCOL VERSION 2.1 STUDY CODE: BV-402 (FICTIONAL STUDY IDENTIFIER) DATE OF APPROVAL: MARCH 15, 2025 ================================================================================ SECTION 4: PARTICIPANT ELIGIBILITY CRITERIA 4.1 Inclusion Criteria Candidates are eligible for enrollment only if all of the following criteria apply: 1. Age 18 years or older at the time of signing informed consent. 2. Histologically or cytologically confirmed metastatic solid tumor refractory to standard systemic therapy. 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 4. Adequate bone marrow and organ function documented within fourteen (14) days prior to Cycle 1, Day 1: a. Absolute neutrophil count (ANC) >= 1,500/mcL. b. Platelet count >= 100,000/mcL. c. Total serum bilirubin <= 1.5 x upper limit of normal (ULN). d. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 x ULN. e. Serum creatinine <= 1.5 x ULN or calculated creatinine clearance >= 50 mL/min. 5. Prior systemic anti-cancer therapy, including targeted therapies and immunotherapy, must have concluded at least twenty-eight (28) days prior to Cycle 1, Day 1. 4.2 Exclusion Criteria Candidates are excluded from enrollment if any of the following criteria apply: 1. Active or untreated central nervous system (CNS) metastases. 2. Uncontrolled intercurrent illness including active systemic bacterial or viral infection. 3. Known positive serology for Human Immunodeficiency Virus (HIV) or active Hepatitis B/C. 4. History of Grade 3 or higher immune-related pneumonitis or myocarditis from prior checkpoint inhibitors. SECTION 5: INVESTIGATIONAL PRODUCT DOSAGE AND ADMINISTRATION 5.1 Dosing Schedule Investigational product BV-402 will be administered as an intravenous (IV) infusion over 60 minutes (+/- 10 minutes) on Day 1 of each fourteen (14) day treatment cycle (every two weeks, Q2W). The starting dose for Cohort 1 is 150 mg. 5.2 Dose Escalation and Dose Reductions Intra-patient dose escalation to 225 mg is permitted after Cycle 3 if no Grade >= 2 treatment-related adverse events are observed. If dose reduction is required due to adverse drug reactions: - First dose reduction (Level -1): 120 mg Q2W. - Second dose reduction (Level -2): 90 mg Q2W. - Patients requiring more than two dose reductions must be permanently discontinued from study treatment. SECTION 7: SAFETY REPORTING AND REGULATORY MONITORING 7.3 Serious Adverse Event (SAE) Escalation The Principal Investigator must report any Serious Adverse Event (SAE), whether deemed drug-related or unrelated, to the Sponsor Medical Monitor within seventy-two (72) hours of site awareness. ================================================================================ RECORD 2: CLINICAL STUDY PROTOCOL — PROTOCOL AMENDMENT 3.0 STUDY CODE: BV-402 (SUBSTANTIVE SAFETY AMENDMENT) DATE OF APPROVAL: AUGUST 22, 2026 ================================================================================ SECTION 4: PARTICIPANT ELIGIBILITY CRITERIA 4.1 Inclusion Criteria Candidates are eligible for enrollment only if all of the following criteria apply: 1. Age 18 years or older at the time of signing informed consent. 2. Histologically or cytologically confirmed metastatic solid tumor refractory to standard systemic therapy. 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 4. Adequate bone marrow and organ function documented within seven (7) days prior to Cycle 1, Day 1: a. Absolute neutrophil count (ANC) >= 1,500/mcL. b. Platelet count >= 100,000/mcL. c. Total serum bilirubin <= 1.2 x ULN (tightened from 1.5 x ULN). d. Serum AST and ALT <= 1.5 x ULN (tightened from 2.5 x ULN); in patients with documented, radiographically verified hepatic metastases, AST and ALT <= 2.5 x ULN remains acceptable. e. Serum creatinine <= 1.2 x ULN or calculated creatinine clearance >= 60 mL/min. 5. Prior systemic anti-cancer therapy, including targeted therapies and immunotherapy, must have concluded at least forty-two (42) days prior to Cycle 1, Day 1 (increased from 28 days to ensure comprehensive immune washout). 4.2 Exclusion Criteria Candidates are excluded from enrollment if any of the following criteria apply: 1. Active or untreated central nervous system (CNS) metastases. 2. Uncontrolled intercurrent illness including active systemic bacterial or viral infection. 3. Known positive serology for HIV or active Hepatitis B/C. 4. History of Grade 2 or higher immune-related pneumonitis, colitis, nephritis, or myocarditis from prior checkpoint inhibitors (broadened exclusion threshold from Grade 3 to Grade 2). 5. Concomitant use of strong CYP3A4 inhibitors or inducers within fourteen (14) days of study initiation. SECTION 5: INVESTIGATIONAL PRODUCT DOSAGE AND ADMINISTRATION 5.1 Dosing Schedule Investigational product BV-402 will be administered as an intravenous (IV) infusion over 60 minutes on Day 1 of each fourteen (14) day cycle (Q2W). Following the observation of two dose-limiting hepatic toxicities (DLTs) in Cohort 2 under Protocol v2.1, the recommended starting dose for all subsequent cohorts is reduced to 100 mg Q2W. Intra-patient dose escalation is formally terminated and prohibited. 5.2 Dose Reductions If dose reduction is required due to adverse drug reactions: - Dose reduction (Level -1): 75 mg Q2W. - Dose reduction below 75 mg is not permitted. Any patient experiencing recurrent Grade >= 2 toxicity at the 75 mg dose level must be permanently discontinued from study treatment. SECTION 7: SAFETY REPORTING AND REGULATORY MONITORING 7.3 Expedited Safety Reporting The Principal Investigator must report any Serious Adverse Event (SAE), Grade >= 3 hepatotoxicity, or suspected immune-related adverse event (irAE) to the Sponsor Medical Monitor and reviewing Institutional Review Board (IRB) within twenty-four (24) hours of site awareness (expedited from 72 hours).