Safety,Tolerability, Pharmacokinetics, and Efficacy of YL211 in Patients With Advanced Solid Tumors

A Phase 1, Multicenter, Open-Label, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of YL211 in Patients With Advanced Solid Tumors

This is a multicenter, open-label, Phase 1 study. The study will enroll subjects with advanced solid tumors. It consists of six parts. Objectives for Dose-Escalation Parts (Part 1 and Part 4) To evaluate the safety and tolerability of YL211 as monotherapy in patients with selected advanced solid tumors (Part 1) and in combination with pembrolizumab in patients with second or third line locally advanced unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) (Part 4) To determine the maximum tolerated dose (MTD) and select the recommended expansion dose(s) (RED(s)) of YL211 as monotherapy in patients with advanced solid tumors (Part 1) and in combination with pembrolizumab in patients with second line locally advanced unresectable or metastatic non-squamous NSCLC (Part 4) Objectives for Backfill Enrollment Parts (Part 2 and Part 5) To better estimate and characterize the safety and efficacy of YL211 as monotherapy in patients with metastatic colorectal cancer (mCRC) or locally advanced unresectable or metastatic NSCLC (Part 2) and in combination with pembrolizumab in patients with previously untreated locally advanced unresectable or metastatic non-squamous NSCLC (Part 5) To select the RED(s) of YL211 as monotherapy in patients with metastatic colorectal cancer (mCRC) or locally advanced unresectable or metastatic NSCLC (Part 2) and in combination with pembrolizumab in patients with previously untreated locally advanced unresectable or metastatic non-squamous NSCLC (Part 5) Objectives for the Dose-Expansion Parts (Part 3 and Part 6) To further characterize the safety and efficacy of YL211 as monotherapy (Part 3) in patients with locally advanced unresectable or metastatic non-squamous or squamous NSCLC and in combination with pembrolizumab in patients with previously untreated locally advanced unresectable or metastatic non- squamous NSCLC (Part 6) To compare the clinical activity of YL211 in combination with pembrolizumab against pembrolizumab, pemetrexed, and platinum-based chemotherapy (cisplatin or carboplatin) in participants with previously untreated advanced unresectable or metastatic non-squamous NSCLC (Part 6)

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: YL211; Drug: YL211+Pembrolizumab; Drug: YL211 + Pembro or Pembro+ Pemetrexed + (Carboplatin or Cisplatin)

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: MediLink Study Team; Phone Number: +86 0512-62858368; Email: clinicaltrials@medilinkthera.com

Study Locations

• Australia
  • Melbourne, Australia
    • Recruiting
    • Monash Health
    • Principal Investigator: Sophia Frentzas
    • Contact: Sophia Frentzas; Email: sophia.frentzas@monash.edu
  • New South Wales
    • Gosford, New South Wales, Australia, 2250
      • Recruiting
      • Gosford Hospital
      • Contact: site coordinator
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • One Clinical Research - Nedlands
      • Contact: site coordinator
• Canada
  • Ottawa, Canada
    • Recruiting
    • The Ottawa Hospital - General Campus
    • Contact: Jura Nakamura; Email: junakamura@ohri.ca
    • Principal Investigator: Scott Laurie
  • Toronto
    • Toronto, Toronto, Canada
      • Recruiting
      • Princess Margaret Hospital
      • Principal Investigator: Albiruni Razak
      • Contact: Albiruni Razak; Email: Albiruni.razak@uhn.ca
• China
  • Chengdu, China
    • Recruiting
    • West China Hospital, Sichuan University
    • Principal Investigator: Yan Zhang
    • Contact: Yan Zhang; Email: 18980601166@qq.com
  • Guangzhou, China
    • Recruiting
    • Sun Yat-sen University Cancer Center
    • Principal Investigator: Ruihua Xu
    • Contact: Danyun Ruan; Email: ruandy1@sysucc.org.cn
    • Sub-Investigator: Danyun Ruan
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100029
      • Recruiting
      • China-Japan Friendship Hospital
      • Contact: site coordinator
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The First Affiliated Hospital - Zhejiang University School of Medicine
      • Contact: site coordinator
    • Wenzhou, Zhejiang, China, 325000
      • Recruiting
      • Wenzhou Medical University - The First Affiliated Hospital
      • Contact: site coordinator
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Hospital - Anschutz Cancer Pavilion
      • Contact: Ashley Fisher; Email: ASHLEY.R.FISHER@CUANSCHUTZ.EDU
      • Principal Investigator: Antonio Jimeno
    • Denver, Colorado, United States, 80218-1238
      • Recruiting
      • Sarah Cannon Research Institute (SCRI) at HealthONE
      • Principal Investigator: Jason Henry
      • Contact: Jason Henry; Email: Jason.Henry2@sarahcannon.com
  • Connecticut
    • North Haven, Connecticut, United States, 06473-2142
      • Recruiting
      • Yale School of Medicine - Yale Cancer Center - Smilow Cancer Hospital Care Centers - North Haven
      • Principal Investigator: Michael Cecchini
      • Contact: Anastasio Gabrielle; Email: gabrielle.anastasio@yale.edu
  • Florida
    • Orlando, Florida, United States, 32827
      • Recruiting
      • Sarah Cannon Research Institute at Florida Cancer Specialists
      • Contact: Elizabeth Gilmore; Email: Elizabeth.Griffith@scri.com
      • Principal Investigator: Cesar Perez
    • Sarasota, Florida, United States, 34232-6422
      • Recruiting
      • Florida Cancer Specialists & Research Institute (FCS) - Sarasota Cattlemen Office
      • Principal Investigator: Manish Patel
      • Contact: Carly Taylor; Email: ctaylor@flcancer.com
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Recruiting
      • Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
      • Contact: site coordinator
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • University of Cincinnati Vontz Center for Molecular Studies
      • Contact: site coordinator
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas - MD Anderson Cancer Center
      • Contact: Coordinator Clinical operation director; Email: RA@medilinkthera.com
    • Houston, Texas, United States, 77055
      • Recruiting
      • Next Oncology - Houston
      • Contact: site coordinator
    • Irving, Texas, United States, 75039
      • Recruiting
      • Next Oncology - Dallas
      • Contact: Erica Torres; Email: etorres@nextoncology.com
      • Principal Investigator: Shiraj Sen
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • NEXT San Antonio
      • Contact: Coordinator Clinical operation director; Email: RA@medilinkthera.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Informed of the trial before the start of the trial and voluntarily sign their name and date on the ICF.
2. Aged ≥18 years.
3. Be able and willing to comply with protocol visits and procedures.
4. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or
5. Adequate organ and bone marrow function.

For Part 1: History of an advanced solid tumors (including locally advanced unresectable or metastatic NSCLC, metastatic colorectal carcinoma (mCRC), advanced gastric adenocarcinoma (GAC)/ gastroesophageal junction adenocarcinoma (GEJA), pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC), intrahepatic biliary tract cancer (ih-BTC), and head and neck squamous cell carcinoma (HNSCC) who failed currently available standard therapies and are not amenable to surgical resection, or for whom no available standard therapy or no other approved therapeutic options that have demonstrated clinical benefit.

For Part 2: For patients with CRC: History of histologically or cytologically confirmed diagnosis of metastatic CRC and at least 2 prior regimens of standard treatment For patients with NSCLC: History of histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic NSCLC and no more than 2 lines of prior cytotoxic systemic therapy in the locally advanced or metastatic setting.

For Part 3: History of histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic non-squamous (Part 3A) or squamous (Part 3B) NSCLC and no more than 2 lines of prior systemic therapy

For Part 4: History of histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic non-squamous NSCLC who have progressed on or after 1 or 2 prior lines of systemic therapy

For Part 5 and Part 6 Histologically or cytologically documented locally advanced unresectable or metastatic non-squamous NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy and no prior systemic treatment for advanced unresectable or metastatic NSCLC

Exclusion Criteria:

1. Prior treatment with an agent targeting c-MET (including antibody, ADC, chimeric antigen receptor T cell [CAR-T], and other drugs) with the exception of prior treatment with MET-targeted TKIs which are allowed.
2. Previously received an ADC consisting of a TopoI
3. Received continuous systemic steroids therapy for more than 28 days or require long-term (≥ 28 days) use of systemic steroids therapy within 28 days before the first administration, or have other acquired or congenital immune deficiency diseases. (Note: The protocol lists specific situational exceptions immediately following this clause).
4. A history of leptomeningeal carcinomatosis or carcinomatous meningitis

5. Brain metastasis, except for the following situations:

   Participants with asymptomatic brain metastasis who do not require immediate local or systemic treatment (such as mannitol or steroids, surgery, or radiotherapy) are allowed to be enrolled If the participant's brain metastasis is treated and the condition of the metastasis is stable (brain imaging examination at least 2 weeks before the first administration shows that the lesion is stable, there is no evidence of new or original brain metastasis enlargement, there are no new neurological symptoms, and immediate local or systemic treatment is not required), admission is allowed

6. Clinically significant concomitant pulmonary disease, including but not limited to:

A history of drug-induced pneumonitis A history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that requires steroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1; YL211 Monotherapy Dose Esclation	Drug: YL211; Patients will be treated with YL211 intravenous (IV) infusion only.
Experimental: Part 2; YL211 Monotherapy Backfill	Drug: YL211; Patients will be treated with YL211 intravenous (IV) infusion only.
Experimental: Part 3; YL211 Monotherapy Dose Expansion	Drug: YL211; Patients will be treated with YL211 intravenous (IV) infusion only.
Experimental: Part 4; YL211 + Pembro Combination Therapy Dose Esclation	Drug: YL211+Pembrolizumab; Patients will be treated with YL211 and Pembro by infusion.
Experimental: Part 5; YL211 + Pembro Combination Therapy Backfill	Drug: YL211+Pembrolizumab; Patients will be treated with YL211 and Pembro by infusion.
Active Comparator: Part 6; YL211 + Pembro Combination Therapy or Pembro + Chemo Combination Therapy Dose Expansion	Drug: YL211 + Pembro or Pembro+ Pemetrexed + (Carboplatin or Cisplatin); participants will receive therapy YL211 + Pembro or Pembro+ Pemetrexed + (Carboplatin or Cisplatin) by infusion.(Part 6)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nature and frequency of adverse events (AEs) with severity determined according to NCI CTCAE v5.0 (Part 1 and Part 4)	AE's	Approximately within 36 months
Nature and frequency of dose-limiting toxicities (DLTs) (Part 1 and Part 4)	DLTs	Approximately within 36 months
Nature and frequency of AEs with severity, physical examination findings (including ECOG PS), vital sign measurements, standard clinical laboratory parameters, SpO2 measurements, ECG parameters, and ECHO findings (Part 2 and Part 5)	Safety	Approximately within 36 months
ORR assessed using RECIST version 1.1 (Part 2 and Part 5)	Efficacy	Approximately within 36 months
PFS using RECIST version 1.1 defined as the time interval of randomization to the date of first documentation of PD or death due to any cause, whichever occurs first (Part 3 and Part 6)	Efficacy	approximately 36 months
Nature and frequency of AEs with severity, physical examination findings (including ECOG PS), vital sign measurements, standard clinical laboratory parameters, SpO2 measurements, ECG parameters, and ECHO findings (Part 3 and Part 6)	Safety	approximately within 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
physical examination findings (including Eastern Cooperative Oncology Group performance status; ECOG PS), vital sign measurements, standard clinical laboratory parameters, SpO2 measurements, ECG parameters, and ECHO findings (Part 1 and Part 4)	other safety endpoints	Approximately within 36 months
PK enpoints (Part 1 and Part 4)	Pharmacokinetic endpoints: for each participant will be estimated using standard non-compartmental methods. Descriptive statistics will be provided for all serum concentration data and PK parameter values, with a break down by dose level/cohort as appropriate. PK parameters of YL211-ADC, YL211-TAb, unconjugated payload YL0010014, metabolite YL0010034 and if applicable, other potential metabolite(s), include but not limited to area under the curve (AUC), maximum concentration (Cmax), trough concentration (Ctrough), time of maximum observed concentration (Tmax), clearance (CL), volume of distribution (Vd), and half-life time (t1/2)	Approximately within 36 months
Incidence of anti-YL211 antibody (ADA) (Part 1 and Part 4)	ADA	Approximately within 36 months
Efficacy endpoints (Part 1 and Part 4)	Tumor response will be evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Efficacy variables include objective response rate (ORR, the sum of complete response [CR] rate and partial response [PR] rate), disease control rate (DCR, the sum of CR rate, PR rate, and stable disease [SD] rate), duration of response (DoR), duration of SD, time to response (TTR), and progression free survival (PFS), overall survival (OS), percent change in target lesion, time on therapy of the most recent prior regimen the participant received and that of YL211. The efficacy variable(s) will be also evaluated at 18 weeks after Day 1 of Cycle 1.	approximately 36 months
PK parameters of YL211-ADC, YL211-TAb, unconjugated payload YL0010014, and if applicable, potential metabolite(s), including but not limited to AUC, Cmax, Ctrough, Tmax, CL, Vd, and t1/2 (Part 2 and Part 5)	PK	approximately 36 months
DCR, DoR, TTR, PFS, OS, and best tumor response assessed using RECIST version 1.1 (Part 2 and Part 5)		approximately 36mo
Incidence of ADA (Part 2 and Part 5)		approximately 36mo
c-MET protein expression level in tumor tissues and its relationship with efficacy endpoints (Part 5)		approximately 36mo
Plasma or serum concentration of YL211-ADC, YL211-TAb, unconjugated payload YL0010014, and if applicable, potential metabolite(s), at specified time points (Part 3 and Part 6)		approximately 36mo
Incidence of ADA (Part 3 and Part 6)		approximately 36mo
ORR, DCR, DoR, TTR, OS, and best tumor response assessed using RECIST version 1.1 (Part 3 and Part 6)		approximately 36mo
c-MET protein expression level in tumor tissues and its relationship with efficacy endpoints (Part 3 and Part 6)		Approximately 36mo

Other Outcome Measures

Outcome Measure	Time Frame
Characterization of genomic alterations that are predictive of response to YL211	Approximately within 36 months
The use of circulating tumor DNA (ctDNA) to monitor response to YL211 treatment	Approximately within 36 months

Collaborators and Investigators

• Sponsor: MediLink Therapeutics (Suzhou) Co., Ltd.
• Collaborators: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2024
• Primary Completion (Estimated): June 30, 2031
• Study Completion (Estimated): June 30, 2031

Study Registration Dates

• First Submitted: March 26, 2024
• First Submitted That Met QC Criteria: April 22, 2024
• First Posted (Actual): April 25, 2024

Study Record Updates

• Last Update Posted (Actual): June 29, 2026
• Last Update Submitted That Met QC Criteria: June 24, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Organic Chemicals; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Platinum Compounds; Carboplatin; Cisplatin
• Other Study ID Numbers: YL211-INT-101-01

Drug and device information, study documents

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