Clinical trial NCT06629597: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Nasopharyngeal Carcinoma
Lead sponsor: MediLink Therapeutics (Suzhou) Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-10-08
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. 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.
2. Previously received B7-H3-targeted drug therapy, including antibody, antibody-drug conjugate (ADC), and chimeric antigen receptor T cell (CAR-T).
3. Prior treatment with a topoisomerase I inhibitor or an antibody-drug conjugate containing a topoisomerase I inhibitor.
4. Inadequate washout period for prior anti-tumor treatment before the first dose of study drug.
5. 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.
6. Received systemic steroids or other immunosuppressive therapy within 2 weeks before the first dose of study drug.
7. Received any live vaccine within 4 weeks before the first dose of study drug or intend to receive a live vaccine during the study.
8. Presence of brain stem or meningeal metastases, spinal cord metastases or compression.
9. 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.
10. Has an uncontrolled concurrent disease.
11. Presence of severe uncontrolled cardiovascular disorder.
12. History of interstitial lung disease (ILD) or pneumonitis that required corticosteroids, or current ILD/ pneumonitis.
13. Concomitant pulmonary disorder leading to clinically severe respiratory impairment.
14. Chronic autoimmune or inflammatory diseases requiring systemic therapy within 2 years prior to the first dose or currently receiving systemic therapy.
15. Clinical symptoms of pleural effusion, pericardial effusion, or ascites or requiring relevant repeated drainage.
16. Serious infections within 4 weeks prior to the first dose.
17. Known active pulmonary tuberculosis (TB).
18. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
19. Unresolved toxicities from previous antitumor therapy.
20. 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.
21. Pregnancy, breastfeeding, or women planning to become pregnant or breastfeed during the study.
22. 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.

Primary outcomes:
measure: 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).
timeFrame: Approximately within 36 months
measure: To compare the OS of YL201 versus investigator's choice of chemotherapy in recurrent or metastatic nasopharyngeal carcinoma.
timeFrame: Approximately within 36 months
Secondary outcomes:
measure: To compare the ORR of YL201 versus investigator's choice of chemotherapy in recurrent or metastatic nasopharyngeal carcinoma assessed by Investigator.
timeFrame: Approximately within 36 months
measure: To compare the PFS of YL201 versus investigator's choice of chemotherapy in recurrent or metastatic nasopharyngeal carcinoma assessed by BICR and Investigator.
timeFrame: Approximately within 36 months
measure: 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.
timeFrame: Approximately within 36 months
measure: 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.
timeFrame: Approximately within 36 months
measure: 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.
timeFrame: Approximately within 36 months
measure: Evaluate the incidence and severity of adverse events (AEs) of YL201
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter AUC
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter Cmax
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter Ctrough
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter CL
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter Vd
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter t1/2
timeFrame: Approximately within 36 months
measure: Assessment of the number of subjects who are Anti-Drug Antibody (ADA)-positive at any time and who have a treatment-emergent ADA.
timeFrame: Approximately within 36 months
measure: Assessment of B7H3 expression level in tumor tissue and the correlation between the expression level and the efficacy of YL201.
timeFrame: Approximately within 36 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
References: