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

NCT06384352
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Phase
Phase 1
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Recruitment status
Recruiting
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Participants
500
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Lead sponsor
MediLink Therapeutics (Suzhou) Co., Ltd.
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Start date
2024-05-01
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Number of sites
21
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Summary
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)
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Short title
Safety,Tolerability, Pharmacokinetics, and Efficacy of YL211 in Patients With Advanced Solid Tumors
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Official title
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
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2031-06-30
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First posted
2024-04-25
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Registry last updated
2026-08-13
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Primary completion date
2031-06-30
clinicaltrials.gov
Start date
2024-05-01
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Participants
500
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Participant count basis
Estimated
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Planned participants
500
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Protocol amendments
5
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Number of sites
21
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Registry sponsor category
Industry
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Lead sponsor
MediLink Therapeutics (Suzhou) Co., Ltd.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06384352
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ClinicalTrials.gov ID
NCT06384352
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Registry record
Open registry record
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Allocation
Not randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Nature and frequency of adverse events (AEs) with severity determined according to NCI CTCAE v5.0 (Part 1 and Part 4)

    Timeframe: Approximately within 36 months

    AE's

  2. Nature and frequency of dose-limiting toxicities (DLTs) (Part 1 and Part 4)

    Timeframe: Approximately within 36 months

    DLTs

  3. 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)

    Timeframe: Approximately within 36 months

    Safety

  4. ORR assessed using RECIST version 1.1 (Part 2 and Part 5)

    Timeframe: Approximately within 36 months

    Efficacy

  5. 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)

    Timeframe: approximately 36 months

    Efficacy

  6. 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)

    Timeframe: approximately within 36 months

    Safety

  1. 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)

    Timeframe: Approximately within 36 months

    other safety endpoints

  2. PK enpoints (Part 1 and Part 4)

    Timeframe: Approximately within 36 months

    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)

  3. Incidence of anti-YL211 antibody (ADA) (Part 1 and Part 4)

    Timeframe: Approximately within 36 months

    ADA

  4. Efficacy endpoints (Part 1 and Part 4)

    Timeframe: approximately 36 months

    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.

  5. 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)

    Timeframe: approximately 36 months

    PK

  6. DCR, DoR, TTR, PFS, OS, and best tumor response assessed using RECIST version 1.1 (Part 2 and Part 5)

    Timeframe: approximately 36mo

  7. Incidence of ADA (Part 2 and Part 5)

    Timeframe: approximately 36mo

  8. c-MET protein expression level in tumor tissues and its relationship with efficacy endpoints (Part 5)

    Timeframe: approximately 36mo

  9. 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)

    Timeframe: approximately 36mo

  10. Incidence of ADA (Part 3 and Part 6)

    Timeframe: approximately 36mo

  11. ORR, DCR, DoR, TTR, OS, and best tumor response assessed using RECIST version 1.1 (Part 3 and Part 6)

    Timeframe: approximately 36mo

  12. c-MET protein expression level in tumor tissues and its relationship with efficacy endpoints (Part 3 and Part 6)

    Timeframe: Approximately 36mo

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  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

  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

Sources for eligibility
clinicaltrials.gov

  • University of Colorado Hospital - Anschutz Cancer PavilionAurora, United StatesRecruiting
  • Sarah Cannon Research Institute (SCRI) at HealthONEDenver, United StatesRecruiting
  • Yale School of Medicine - Yale Cancer Center - Smilow Cancer Hospital Care Centers - North HavenNorth Haven, United StatesRecruiting
  • Sarah Cannon Research Institute at Florida Cancer SpecialistsOrlando, United StatesRecruiting
  • Florida Cancer Specialists & Research Institute (FCS) - Sarasota Cattlemen OfficeSarasota, United StatesRecruiting
  • Comprehensive Cancer Centers of Nevada (CCCN) - Central ValleyLas Vegas, United StatesRecruiting
  • University of Cincinnati Vontz Center for Molecular StudiesCincinnati, United StatesRecruiting
  • The University of Texas - MD Anderson Cancer CenterHouston, United StatesRecruiting
  • NEXT Oncology - HoustonHouston, United StatesRecruiting
  • NEXT Oncology - DallasIrving, United StatesRecruiting
  • NEXT San AntonioSan Antonio, United StatesRecruiting
  • Gosford HospitalGosford, AustraliaRecruiting
  • One Clinical Research - NedlandsNedlands, AustraliaRecruiting
  • Monash HealthMelbourne, AustraliaRecruiting
  • Princess Margaret HospitalToronto, CanadaRecruiting
  • The Ottawa Hospital - General CampusOttawa, CanadaRecruiting
  • China-Japan Friendship HospitalBeijing, ChinaRecruiting
  • The First Affiliated Hospital - Zhejiang University School of MedicineHangzhou, ChinaRecruiting
  • Wenzhou Medical University - The First Affiliated HospitalWenzhou, ChinaRecruiting
  • West China Hospital, Sichuan UniversityChengdu, ChinaRecruiting
  • Sun Yat-sen University Cancer CenterGuangzhou, ChinaRecruiting
Sources for sites
clinicaltrials.gov

Related records

Drugs (3)

Collaborators (1)

Lead sponsors (1)

Targets (4)