A Phase 1, Multicenter, Open-Label, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of YL211 in Patients With Advanced Solid Tumors
This is a multicenter, open-label, Phase 1 study. The study will enroll subjects with advanced solid tumors. It consists of six parts. Objectives for Dose-Escalation Parts (Part 1 and Part 4) To evaluate the safety and tolerability of YL211 as monotherapy in patients with selected advanced solid tumors (Part 1) and in combination with pembrolizumab in patients with second or third line locally advanced unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) (Part 4) To determine the maximum tolerated dose (MTD) and select the recommended expansion dose(s) (RED(s)) of YL211 as monotherapy in patients with advanced solid tumors (Part 1) and in combination with pembrolizumab in patients with second line locally advanced unresectable or metastatic non-squamous NSCLC (Part 4) Objectives for Backfill Enrollment Parts (Part 2 and Part 5) To better estimate and characterize the safety and efficacy of YL211 as monotherapy in patients with metastatic colorectal cancer (mCRC) or locally advanced unresectable or metastatic NSCLC (Part 2) and in combination with pembrolizumab in patients with previously untreated locally advanced unresectable or metastatic non-squamous NSCLC (Part 5) To select the RED(s) of YL211 as monotherapy in patients with metastatic colorectal cancer (mCRC) or locally advanced unresectable or metastatic NSCLC (Part 2) and in combination with pembrolizumab in patients with previously untreated locally advanced unresectable or metastatic non-squamous NSCLC (Part 5) Objectives for the Dose-Expansion Parts (Part 3 and Part 6) To further characterize the safety and efficacy of YL211 as monotherapy (Part 3) in patients with locally advanced unresectable or metastatic non-squamous or squamous NSCLC and in combination with pembrolizumab in patients with previously untreated locally advanced unresectable or metastatic non- squamous NSCLC (Part 6) To compare the clinical activity of YL211 in combination with pembrolizumab against pembrolizumab, pemetrexed, and platinum-based chemotherapy (cisplatin or carboplatin) in participants with previously untreated advanced unresectable or metastatic non-squamous NSCLC (Part 6)
• Informed of the trial before the start of the trial and voluntarily sign their name and date on the ICF.
• Aged ≥18 years.
• Be able and willing to comply with protocol visits and procedures.
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or
• Adequate organ and bone marrow function.
⁃ For Part 1: History of an advanced solid tumors (including locally advanced unresectable or metastatic NSCLC, metastatic colorectal carcinoma (mCRC), advanced gastric adenocarcinoma (GAC)/ gastroesophageal junction adenocarcinoma (GEJA), pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC), intrahepatic biliary tract cancer (ih-BTC), and head and neck squamous cell carcinoma (HNSCC) who failed currently available standard therapies and are not amenable to surgical resection, or for whom no available standard therapy or no other approved therapeutic options that have demonstrated clinical benefit.
⁃ For Part 2: For patients with CRC: History of histologically or cytologically confirmed diagnosis of metastatic CRC and at least 2 prior regimens of standard treatment For patients with NSCLC: History of histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic NSCLC and no more than 2 lines of prior cytotoxic systemic therapy in the locally advanced or metastatic setting.
⁃ For Part 3: History of histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic non-squamous (Part 3A) or squamous (Part 3B) NSCLC and no more than 2 lines of prior systemic therapy
⁃ For Part 4: History of histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic non-squamous NSCLC who have progressed on or after 1 or 2 prior lines of systemic therapy
⁃ For Part 5 and Part 6 Histologically or cytologically documented locally advanced unresectable or metastatic non-squamous NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy and no prior systemic treatment for advanced unresectable or metastatic NSCLC