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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: YL201; Drug: Docetaxel; Drug: Capecitabine; Drug: Gemcitabine

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.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xianfeng Zhu; Phone Number: +86 512 6285 8368; Email: xianfeng.zhu@medilinkthera.com
• Study Contact Backup: Name: Xian Zhang; Phone Number: +86 512 6285 8368; Email: zhangxian@medilinkthera.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Site Coordinator

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: YL201; Participants are randomized to receive YL201 monotherapy intravenously on Day 1 of each 3-week cycle at RP3D dose level, until progressive disease (PD), unacceptable toxicity, or withdrawal of consent as specified in the protocol.	Drug: YL201; YL201 will be administered intravenously on Day 1 of each 3-week cycle at RP3D dose level.
Active Comparator: Investigator's choice of chemotherapy, including docetaxel, capecitabine, or gemcitabine; Participants are randomized to receive docetaxel/capecitabine/gemcitabine every 3 weeks per prescribing information, until PD, unacceptable toxicity, or withdrawal of consent as specified in the protocol.	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	ORR is defined as the proportion of subjects who achieve a best overall response (BOR) of complete response (CR) or partial response (PR).	Approximately within 36 months
To compare the OS of YL201 versus investigator's choice of chemotherapy in recurrent or metastatic nasopharyngeal carcinoma.	OS defined as the time interval from the randomization to death from any cause.	Approximately within 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize the PK parameter AUC		Approximately within 36 months
Characterize the PK parameter Cmax		Approximately within 36 months
Characterize the PK parameter Ctrough		Approximately within 36 months
Characterize the PK parameter CL		Approximately within 36 months
Characterize the PK parameter Vd		Approximately within 36 months
Characterize the PK parameter t1/2		Approximately within 36 months
Assessment of B7H3 expression level in tumor tissue and the correlation between the expression level and the efficacy of YL201.		Approximately within 36 months
To compare the ORR of YL201 versus investigator's choice of chemotherapy in recurrent or metastatic nasopharyngeal carcinoma assessed by Investigator.	ORR is defined as the proportion of subjects who achieve a best overall response (BOR) of complete response (CR) or partial response (PR).	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.	PFS defined as the time interval from randomization to the first documented PD or death due to any cause, whichever occurs first.	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.	DOR defined as the time interval from the first documentation of response (CR or PR) to the first documentation of PD or death, whichever occurred first.	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.	DCR is defined as the proportion of subjects with a BOR of CR, PR, or stable disease (SD).	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.	TTR is defined as the time interval from randomization to the first documentation of response (CR or PR).	Approximately within 36 months
Evaluate the incidence and severity of adverse events (AEs) of YL201	AEs are assessed based on NCI CTCAE v5.0.	Approximately within 36 months
Assessment of the number of subjects who are Anti-Drug Antibody (ADA)-positive at any time and who have a treatment-emergent ADA.		Approximately within 36 months

Collaborators and Investigators

• Sponsor: MediLink Therapeutics (Suzhou) Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: September 24, 2024
• First Submitted That Met QC Criteria: October 3, 2024
• First Posted (Actual): October 8, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 6, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Carcinoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Capecitabine; Gemcitabine
• Other Study ID Numbers: YL201-CN-301-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No