A Phase 1, Multicenter, Open-Label, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of YL201 in Patients With Advanced Solid Tumors

Eligibility: Inclusion Criteria
  •   Common Inclusion Criteria (Part 1 and Part 2)
  •   * Informed of the trial before the start of the trial and voluntarily sign their name and date on the ICF
  •   * Aged >=18 years
  •   * Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1
  •   * Adequate organ and bone marrow function
  •   * Female patients of childbearing potential must agree to use a highly effective form of contraception and not donate, or retrieve for their own use, ova from the time of screening and throughout the study period, and for at least 6 months after the last dose of study drug. Male patients must agree to use a highly effective form of contraception and not freeze or donate sperm from the time of screening and throughout the study period, and for at least 6 months after the last dose of study drug
  •   * Life expectancy of >=3 months
  •   * Able and willing to comply with protocol visits and procedures
  •   * Pathologically confirmed diagnosis of an advanced solid tumor for which prior standard treatment had proven to be ineffective or intolerable, or no standard treatment is available
  •   Additional Inclusion Criteria for Part 1
  •   * Have at least 1 evaluable tumor lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Participants with prostate cancer who have bone only disease may be eligible on a case-by-case basis after discussion with the sponsor
  •   Additional Inclusion Criteria for Part 2
  •   * Have at least 1 measurable tumor lesion according to RECIST version 1.1. Participants with prostate cancer who have bone only disease may be eligible on a case-by-case basis after discussion with the sponsor
  •   * Willing to provide archival or fresh tumor tissue samples. Patients who are not able to provide tumor samples or have inadequate samples may be eligible on a case-by-case basis after discussion with the sponsor
Exclusion Criteria
  •   Common Exclusion Criteria (Part 1 and Part 2)
  •   * Intolerant to prior treatment with a topoisomerase I inhibitor or an ADC that consists of a topoisomerase I inhibitor, including but not limited to topotecan, irinotecan, and Dxd
  •   * Concurrent enrollment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study
  •   * Prior systemic anticancer treatment including chemotherapy, molecular targeted therapy, hormonal therapy, immunotherapy, or biological therapy within 3 weeks before the first dose of study drug (use of oral fluorouracil [eg, tegafur and capecitabine] or small molecular targeted therapy within 2 weeks or 5 half-life periods [whichever is shorter] before the first dose; use of mitomycin or nitrosoureas within 6 weeks before the first dose; use of herbal medicine with antitumor indications or nonspecific immunomodulators [eg, thymosin, interferon, and interleukin] within 2 weeks before the first dose)
  •   * Prior radiation therapy, including palliative stereotactic radiation with abdominal, within 4 weeks before the first dose of study drug (if palliative stereotactic radiation therapy without abdominal, within 2 weeks)
  •   * Undergone major surgery (not including diagnostic surgery) within 4 weeks before the first dose of study drug or expect major surgery during the study
  •   * Undergone allogeneic hematopoietic stem cell transplantation (HSCT) before the first dose of study drug, or autologous HSCT within 3 months before the first dose of study drug
  •   * Received systemic steroids (>10 mg/day of prednisone or its equivalent) or other immunosuppressive therapy within 2 weeks before the first dose of study drug. The following are exceptions to this criterion:
  •    1. Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection)
  •    2. Systemic steroids at physiological doses as replacement therapy (eg, physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency)
  •    3. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
  •   * Received any live vaccine within 4 weeks before the first dose of study drug or intend to receive a live vaccine during the study
  •   * A history of leptomeningeal carcinomatosis
  •   * Brain metastases or spinal cord compression unless asymptomatic or treated and stable off steroids and anti-convulsants for at least 2 weeks before the first dose of study drug
  •   * Uncontrolled or clinically significant cardiovascular disease
  •   * A history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that requires steroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
  •   * Clinically significant concomitant pulmonary disease
  •   * Have a diagnosis of Gilbert''s syndrome
  •   * Uncontrolled third-space fluid that requires repeated drainage
  •   * Active gastric and duodenal ulcers, ulcerative colitis, or other gastrointestinal conditions that may cause bleeding or perforation by the investigator''s discretion
  •   * Uncontrolled infection that requires systemic therapy within 1 week before the first dose
  •   * Known human immunodeficiency virus (HIV) infection
  •   * Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Active HBV is defined as hepatitis B core antibody (HBcAb) or hepatitis B surface antigen (HBsAg) positive, and HBV DNA level above ULN at the study site; active HCV is defined as positive hepatitis C antibody and HCV RNA level above ULN at the study site
  •   * Unresolved toxicities from previous anticancer therapy, defined as toxicities not yet resolved to NCI CTCAE Grade =1, baseline, or the level specified in the inclusion/exclusion criteria with the exception of alopecia (any grade), pigmentation (any grade), and peripheral neuropathy (Grade =2). Patients with irreversible toxicity (eg, hearing loss) that is reasonably not expected to be aggravated by the study drug can be enrolled after discussion with the sponsor
  •   * A history of severe hypersensitivity reactions to the drug substances, inactive ingredients in the drug product, or other mAbs
  •   * Women who are breastfeeding or pregnant as confirmed by pregnancy tests performed within 7 days before the first dose
  •   * Any illness, medical condition, organ system dysfunction, or social situation, including but not limited to mental illness or substance/alcohol abuse, deemed by the investigator to be likely to interfere with a patient''s ability to sign informed consent, adversely affect the patient''s ability to cooperate and participate in the study, or compromise the interpretation of study results Additional Exclusion Criteria for Part 2
  •   * Multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other curatively treated solid tumors