A Study of YL202 in Combination With Other Anti-tumor Therapies in Patients With Advanced Solid Tumors

Official title

A Multi-center, Open-Label, Phase Ib/II Study of YL202 in Combination With Anti-tumor Therapy to Evaluate the Safety, Tolerability, and Efficacy in Patients With Advanced Solid Tumors

Overview

This is a multicenter, open-label, phase Ib/II study of YL202 in combination with other anti-tumor therapies to Evaluate the Safety, Tolerability, and Efficacy in Patients with Advanced Solid Tumors

Interventions

• Drug YL202 for injection; Toripalimab injection
  Part 1: YL202 and Toripalimab will be administered intravenously. Part 3: participants will receive escalating doses of YL202 and fixed dose of Toripalimab until YL202 doses for optimization are determined. Dose expansion stage: participants will receive a dose of YL202 not exceeding the maximum dose level achieved during the dose-escalation stage and fixed dose of Toripalimab
• Drug YL202 for injection; Furmonertinib Mesilate Tablets
  Part 2: YL202 will be administered intravenously，Furmonertinib Mesilate Tablets will be administered orally. Dose escalation stage: participants will receive escalating doses of YL202 and fixed dose of Furmonertinib Mesilate until YL202 doses for optimization are determined. Part 4: participants will receive a dose of YL202 not exceeding the maximum dose level achieved during the dose-escalation stage and fixed dose of Furmonertinib Mesilate.

Primary outcome measures

• Nature and frequency of dose-limiting toxicity (DLT) [Time frame: 21 days after the first dose was administered to each subject.]
• Nature and frequency of adverse events (AEs) [Time frame: 42 days after the end of treatment (EOT).]

Secondary outcome measures (9)

• Objective response rate (ORR) [Time frame: Up to approximately 3 years.]
• Characterize Pharmacokinetics (PK) parameter AUC [Time frame: Up to approximately 3 years]
• Characterize Pharmacokinetics (PK) parameter Cmax [Time frame: Up to approximately 3 years]
• Characterize Pharmacokinetics (PK) parameter Ctrough [Time frame: Up to approximately 3 years]
• Characterize Pharmacokinetics (PK) parameter Tmax [Time frame: Up to approximately 3 years]
• Characterize Pharmacokinetics (PK) parameter CL [Time frame: Up to approximately 3 years]
• Characterize Pharmacokinetics (PK) parameter Vd [Time frame: Up to approximately 3 years]
• Characterize Pharmacokinetics (PK) parameter t1/2 [Time frame: Up to approximately 3 years]
• Immunogenicity endpoint: Incidence of anti-YL202 antibody (ADAs). [Time frame: Up to approximately 3 years]

Eligibility criteria

Inclusion criteria

• Informed of the study before the start of the study and voluntarily sign their name and date in the informed consent form (ICF)
• Able and willing to comply with protocol visits and procedures
• Aged between 18 to 75 years
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1
• Previously treated by standard treatment or have not been treated for metastatic setting;
• Adequate organ and bone marrow function.
• Have at least 1 extracranial measurable tumor lesion.
• Adequate archival formalin-fixed paraffin embedded （FFPE） tissue from prior biopsy.

Exclusion criteria

• With prior drug therapy targeting HER3 (including antibodies, antibody-drug conjugates \[ADCs\]), chimeric antigen receptor T-cell immunotherapy (CAR-T), and other drugs).
• Previously intolerant to topoisomerase I inhibitors or ADC therapy composed of topoisomerase I inhibitors.
• Are participating in another clinical study, unless it is an observational (non-interventional) clinical study or in the follow-up period of an interventional study.
• The washout period from the previous anti-tumor therapy is insufficient before the first dose of the investigational product.
• Patients who have received major surgery (excluding diagnostic surgery) within 4 weeks before the first dose of the investigational product or those who are expected to receive major surgery during the study.
• Prior treatment with allogeneic bone marrow transplantation or solid organ transplantation.
• Prior treatment with systemic steroids (prednisone > 10 mg/day or equivalent) or other immunosuppressive treatment within 2 weeks before the first dose of the investigational product.
• Patients who have received any live vaccine within 4 weeks before the first dose of the investigational product or those who plan to receive live vaccine during the study period.
• With meningeal metastasis or cancerous meningitis.
• With brain metastasis or spinal cord compression.
• Patients with uncontrolled or clinically significant cardiovascular diseases.
• Clinically significant complicated pulmonary disorders.
• Patients diagnosed with Gilbert syndrome.
• Those with uncontrolled effusion in the third space requiring repeated drainage.
• With a medical history of gastrointestinal perforation and/or fistula within 6 months before the first dose, or with active gastric and duodenal ulcers, ulcerative colitis, or other gastrointestinal diseases that may lead to hemorrhage or perforation according to the investigator.
• With serious infection before the first dose.
• With known human immunodeficiency virus (HIV) infection.
• With active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• With a medical history of any other primary malignancies within 5 years before the first dose of the investigational product.
• Unrelieved toxicity of previous anti-tumor therapy.
• With a history of severe hypersensitivity to inactive ingredients in the raw materials and drug product or other monoclonal antibodies.
• Lactating women, or women who are confirmed pregnant via a pregnancy test within 3 days before the first dose.
• With any diseases, medical conditions, organ system dysfunction, or social conditions that may interfere with the ability of subjects to sign the ICF, adversely affect the ability of subjects to cooperate and participate in the study, or affect the interpretation of study results, including but not limited to mental illness or substance/alcohol abuse, in the opinion of the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 20 centers

• Anhui Provincial Hospital(The First Affiliated Hospital of Ustc) — Hefei
• Fujian Cancer Hospital — Fuzhou
• Sun Yat-sen University Cancer Center — Guangzhou
• Meizhou People's Hospital（Huangtang Hospital）Meizhou Academy of Medical Sciences — Meizhou
• Ghang xi Medical University Cancer Hospital — Nanning
• Affiliated Hospital Of Hebei University — Baoding
• Harbin Medical University Cancer Hospital — Harbin
• Anyang Cancer Hospital — Anyang
• … and 12 more centers

Identifiers

NCT: NCT07169994 · YL202-CN-204-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗