A Phase III Study of YL201 in Recurrent or Metastatic Nasopharyngeal Carcinoma

Official title

A Randomized, Controlled, Multicenter Phase III Clinical Study of YL201 Versus Investigator's Choice of Chemotherapy in Subjects with Recurrent or Metastatic Nasopharyngeal Carcinoma Who Have Failed Prior PD-(L)1 Inhibitor and At Least Two Lines of Chemotherapy

Overview

This study was designed to compare the efficacy and safety of YL201 with Investigator's choice of chemotherapy in subjects with recurrent or metastatic nasopharyngeal carcinoma who have failed prior PD-(L)1 inhibitor and at least two lines of chemotherapy.

Detailed description

The primary objective of this study is to assess whether treatment with YL201 prolongs overall survival (OS) and increases objective response rate (ORR) by blinded independent central review (BICR) compared with treatment of investigator's choice of chemotherapy among subjects with recurrent or metastatic nasopharyngeal carcinoma.

The secondary objectives of the study are to further evaluate the efficacy, safety, pharmacokinetics, and immunogenicity of YL201, and the correlation between B7-H3 expression level and the efficacy of YL201.

Interventions

• Drug YL201
  YL201 will be administered intravenously on Day 1 of each 3-week cycle at RP3D dose level.
• Drug Docetaxel
  Docetaxel will be administered intravenously at 75 mg/m2 on Day 1 of each 3-week cycle.
• Drug Capecitabine
  Capecitabine will be administered orally at 1000 mg/m2 twice a day (BID) on Days 1 to 14 of each 3-week cycle
• Drug Gemcitabine
  Gemcitabine will be administered intravenously at 1000 mg/m2 on Day 1 and 8 of each 3-week cycle

Primary outcome measures

• To compare the ORR of YL201 versus investigator's choice of chemotherapy in recurrent or metastatic nasopharyngeal carcinoma assessed by BICR based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). [Time frame: Approximately within 36 months]
• To compare the OS of YL201 versus investigator's choice of chemotherapy in recurrent or metastatic nasopharyngeal carcinoma. [Time frame: Approximately within 36 months]

Secondary outcome measures (12)

• To compare the ORR of YL201 versus investigator's choice of chemotherapy in recurrent or metastatic nasopharyngeal carcinoma assessed by Investigator. [Time frame: Approximately within 36 months]
• To compare the PFS of YL201 versus investigator's choice of chemotherapy in recurrent or metastatic nasopharyngeal carcinoma assessed by BICR and Investigator. [Time frame: Approximately within 36 months]
• To compare the DOR of YL201 versus investigator's choice of chemotherapy in subjects with recurrent or metastatic nasopharyngeal carcinoma assessed by BICR and Investigator. [Time frame: Approximately within 36 months]
• To compare the DCR of YL201 versus investigator's choice of chemotherapy in subjects with recurrent or metastatic nasopharyngeal carcinoma assessed by BICR and Investigator. [Time frame: Approximately within 36 months]
• To compare the TTR of YL201 versus investigator's choice of chemotherapy in subjects with recurrent or metastatic nasopharyngeal carcinoma assessed by BICR and Investigator. [Time frame: Approximately within 36 months]
• Evaluate the incidence and severity of adverse events (AEs) of YL201 [Time frame: Approximately within 36 months]
• Characterize the PK parameter AUC [Time frame: Approximately within 36 months]
• Characterize the PK parameter Cmax [Time frame: Approximately within 36 months]
• Characterize the PK parameter Ctrough [Time frame: Approximately within 36 months]
• Characterize the PK parameter CL [Time frame: Approximately within 36 months]
• Characterize the PK parameter Vd [Time frame: Approximately within 36 months]
• Characterize the PK parameter t1/2 [Time frame: Approximately within 36 months]

Eligibility criteria

Inclusion criteria

• Voluntarily sign a written informed consent form (ICF).
• Aged ≥18 years and ≤75 years, male or female.
• ECOG performance status score of 0 or 1.
• Life expectancy ≥ 3 months.
• Histologically or cytologically confirmed recurrent or metastatic nasopharyngeal carcinoma that is not amenable to curative treatment.
• Have failed prior treatment with PD-(L)1 inhibitors and at least two lines of chemotherapy.
• Suitable for treatment with investigator's choice of chemotherapy (docetaxel, capecitabine, or gemcitabine).
• At least one measurable lesion according to RECIST v1.1.
• Subjects are willing to provide the archived or freshly obtained tumor tissue (freshly obtained or archived) for detection of B7-H3 expression
• Adequate organ function.

Exclusion criteria

• History of other malignant tumors within 5 years prior to the first dose of study drug. Subjects who have been cured of other tumors by local therapy, such as basal cell carcinoma, squamous cell carcinoma of skin, bladder cancer in situ, cervical carcinoma in situ, or breast cancer in situ, are not excluded.
• Previously received B7-H3-targeted drug therapy, including antibody, antibody-drug conjugate (ADC), and chimeric antigen receptor T cell (CAR-T).
• Prior treatment with a topoisomerase I inhibitor or an antibody-drug conjugate containing a topoisomerase I inhibitor.
• Inadequate washout period for prior anti-tumor treatment before the first dose of study drug.
• Received radical radiotherapy within 4 weeks prior to the first dose of study drug; local palliative radiation for symptom control is allowed, but treatment must be completed at least 2 weeks prior to the first dose of study drug, and there is no plan for additional radiotherapy to the same lesion.
• Received systemic steroids or other immunosuppressive therapy within 2 weeks before the first dose of study drug.
• Received any live vaccine within 4 weeks before the first dose of study drug or intend to receive a live vaccine during the study.
• Presence of brain stem or meningeal metastases, spinal cord metastases or compression.
• Presence of central nervous system (CNS) metastasis. Participants with treated brain metastases are eligible if the metastases are asymptomatic and stable, and no immediate local or systemic treatment is needed within 2 weeks before the first dose.
• Has an uncontrolled concurrent disease.
• Presence of severe uncontrolled cardiovascular disorder.
• History of interstitial lung disease (ILD) or pneumonitis that required corticosteroids, or current ILD/ pneumonitis.
• Concomitant pulmonary disorder leading to clinically severe respiratory impairment.
• Chronic autoimmune or inflammatory diseases requiring systemic therapy within 2 years prior to the first dose or currently receiving systemic therapy.
• Clinical symptoms of pleural effusion, pericardial effusion, or ascites or requiring relevant repeated drainage.
• Serious infections within 4 weeks prior to the first dose.
• Known active pulmonary tuberculosis (TB).
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• Unresolved toxicities from previous antitumor therapy.
• Known allergy to any component of the study drug; history of severe allergic reactions or known history of severe hypersensitivity to other monoclonal antibodies or recombinant proteins, or history of severe infusion reactions.
• Pregnancy, breastfeeding, or women planning to become pregnant or breastfeed during the study.
• Any illness, medical condition, organ system dysfunction, or social situation deemed by the investigator to be likely to interfere with a subject's ability to sign ICF, adversely affect the subject's ability to cooperate and participate in the study, or compromise the interpretation of study results.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-sen University Cancer Center — Guangzhou

Identifiers

NCT: NCT06629597 · YL201-CN-301-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗