A Study to Compare the Efficacy and Safety of YL201 With Standard Chemotherapy in Patients With Metastatic Pancreatic Cancer After Failure of Gemcitabine-Based Systemic Chemotherapy

A Randomized, Controlled, Multicenter Phase III Study to Evaluate the Efficacy and Safety of YL201 Versus Liposomal Irinotecan in Combination With 5-Fluorouracil/Leucovorin in Participants With Metastatic Pancreatic Ductal Adenocarcinoma Who Have Failed Prior Gemcitabine-based Systemic Therapy

The purpose of this study is to evaluate the safety and efficacy of an investigational B7-H3 antibody drug-conjugate administered as monotherapy, compared with standard of care (SOC) chemotherapy in metastatic pancreatic cancer patients who have failed prior Gemcitabine-based systemic therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Pancreatic Cancer; Pancreatic Ductal Adenocarcinoma (PDAC)
• Intervention / Treatment: Drug: Tambotatug pelitecan; Drug: Liposomal irinotecan; Drug: 5 Fluorouracil; Drug: Leucovorin

• Study Type: Interventional
• Enrollment (Estimated): 320
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: MediLink Study Team; Phone Number: +86 512 62858368; Email: clinicaltrials@medilinkthera.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200127
      • Shanghai Jiaotong University School of Medicine
      • Contact: Study Coordinator

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Participants must voluntarily sign a written informed consent form (ICF) and be willing and able to comply with protocol requirements.
2. Participants must be ≥18 and ≤75 years of age.
3. Participants must have an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
4. Participants must have a life expectancy of at least 3 months.
5. Participants must have histologically or cytologically confirmed incurable metastatic pancreatic ductal adenocarcinoma (PDAC).
6. Participants must have received and failed only one prior line of gemcitabine-based systemic therapy.
7. Participants must have at least one measurable lesion according to RECIST v1.1.
8. Participants must have adequate organ function as defined in the protocol.
9. Participants must agree to follow the contraception requirements specified in the protocol.

Exclusion Criteria:

1. Participants with another malignancy within 5 years before randomization.
2. Participants with pathologically confirmed pancreatic cancer other than PDAC.
3. Participants who have previously received B7-H3-targeted therapy.
4. Participants who have previously received topoisomerase I inhibitor or antibody-drug conjugate containing topoisomerase I inhibitor.
5. Participants who are concurrently enrolled in another clinical study, unless it is an observational, non-interventional study or the participant is in the follow-up period of an interventional study.
6. Participants who have not met the protocol-specified washout requirements for prior systemic therapy, relevant concomitant medications, radiotherapy, or surgery before randomization, or who have not adequately recovered from prior surgery or are planning to undergo major surgery during the study.
7. Participants with protocol-specified exclusionary conditions related to central nervous system (CNS) metastases, history of transplantation, immunosuppressive therapy, live vaccine administration, or autoimmune or inflammatory diseases.
8. Participants with uncontrolled or clinically significant concomitant diseases, including serious gastrointestinal, cardiovascular or cerebrovascular, pulmonary, thromboembolic, bleeding-related, effusion-related, or ascites-related safety risks.
9. Participants with recent serious infection, active infection, active tuberculosis or syphilis, HIV positivity or immunodeficiency, or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
10. Participants with unresolved toxicity from prior anticancer therapy that has not recovered to the level specified in the protocol.
11. Participants with known hypersensitivity to any component of the study treatment, or a history of severe hypersensitivity reactions or severe infusion-related reactions.
12. Participants who are pregnant or breastfeeding, planning to become pregnant or breastfeed, or who have any other medical, psychiatric, social, or compliance-related factors that, in the investigator's opinion, would make them unsuitable for participation in the study.

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: Tambotatug pelitecan; Tambotatug pelitecan, monotherapy	Drug: Tambotatug pelitecan; Drug: Tambotatug pelitecan 2.0mg/kg (maximum 200mg) Intravenous infusion Every 3 weeks Treatment will continue until disease progression or unacceptable toxicity.; Other Names: YL201, Tam-Peli
Active Comparator: Chemotherapy; Active comparator: nal-IRI+5-FU/LV	Drug: Liposomal irinotecan; Liposomal irinotecan Intravenous infusion Every 2 weeks Treatment will continue until disease progression or unacceptable toxicity.; Drug: 5 Fluorouracil; 5 Fluorouracil Intravenous infusion Every 2 weeks Treatment will continue until disease progression or unacceptable toxicity.; Drug: Leucovorin; Leucovorin Intravenous infusion Every 2 weeks Treatment will continue until disease progression or unacceptable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS by BICR	Progression-free Survival (PFS) is assessed by Blinded Independent Central Review（BICR） per response evaluation criteria in solid tumors (RECIST) v1.1	Up to approximately 2 years
OS	OS is defined as the time from randomization until death from any cause.	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS by investigator	PFS per RECIST v1.1, as assessed by Investigator	Up to approximately 2 year
ORR	Objective Response Rate (ORR), as assessed by BICR and Investigator	Up to approximately 2 years
DCR	Disease Control Rate (DCR), as assessed by BICR and Investigator	Up to approximately 2 years
DoR	Duration of Response (DoR), as assessed by BICR and Investigator	Up to approximately 2 years
TTR	Time to Response (TTR), as assessed by BICR and Investigator	Up to approximately 2 years
Adverse Event	The incidence and severity of AEs, SAEs and AESIs per the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 6.0	Up to approximately 2 years
To evaluate the AUC		Up to approximately 2 years
To evaluate the Cmax		Up to approximately 2 years
To evaluate the Ctrough		Up to approximately 2 years
To evaluate the CL		Up to approximately 2 years
To evaluate the Vd		Up to approximately 2 years
To evaluate the t1/2		Up to approximately 2 years
Immunogenicity	Incidence of anti-drug antibodies of YL201	Up to approximately 2 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: August 31, 2026
• First Submitted That Met QC Criteria: September 2, 2026
• First Posted (Actual): September 4, 2026

Study Record Updates

• Last Update Posted (Actual): September 4, 2026
• Last Update Submitted That Met QC Criteria: September 2, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: PDAC; YL201; Tambotatug pelitecan; Tam-Peli
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Enzymes and Coenzymes; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Fluorouracil; Leucovorin; irinotecan sucrosofate
• Other Study ID Numbers: TAISHAN-305

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No