Safety,Tolerability, Pharmacokinetics, and Efficacy of YL211 in Patients With Advanced Solid Tumors (NCT06384352) — China Trial Details

Condition(s) studied

Advanced Solid Tumors

Investigational drug(s) / intervention(s)

YL211YL211+PembrolizumabYL211 + Pembro or Pembro+ Pemetrexed + (Carboplatin or Cisplatin)

YL211: Patients will be treated with YL211 intravenous (IV) infusion only.

YL211+Pembrolizumab: Patients will be treated with YL211 and Pembro by infusion.

YL211 + Pembro or Pembro+ Pemetrexed + (Carboplatin or Cisplatin): participants will receive therapy YL211 + Pembro or Pembro+ Pemetrexed + (Carboplatin or Cisplatin) by infusion.(Part 6)

Study 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)

Eligibility

Sex

ALL

Min age

18 Years

Max age

—

Healthy volunteers

No

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

Primary outcome measure(s)

Nature and frequency of adverse events (AEs) with severity determined according to NCI CTCAE v5.0 (Part 1 and Part 4) — Approximately within 36 months
AE's
Nature and frequency of dose-limiting toxicities (DLTs) (Part 1 and Part 4) — Approximately within 36 months
DLTs
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) — Approximately within 36 months
Safety
ORR assessed using RECIST version 1.1 (Part 2 and Part 5) — Approximately within 36 months
Efficacy
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) — approximately 36 months
Efficacy
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) — approximately within 36 months
Safety

Trial sites (21)

Facility	City	Region	Status
University of Colorado Hospital - Anschutz Cancer Pavilion	Aurora	Colorado	Recruiting
Sarah Cannon Research Institute (SCRI) at HealthONE	Denver	Colorado	Recruiting
Yale School of Medicine - Yale Cancer Center - Smilow Cancer Hospital Care Centers - North Haven	North Haven	Connecticut	Recruiting
Sarah Cannon Research Institute at Florida Cancer Specialists	Orlando	Florida	Recruiting
Florida Cancer Specialists & Research Institute (FCS) - Sarasota Cattlemen Office	Sarasota	Florida	Recruiting
Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley	Las Vegas	Nevada	Recruiting
University of Cincinnati Vontz Center for Molecular Studies	Cincinnati	Ohio	Recruiting
The University of Texas - MD Anderson Cancer Center	Houston	Texas	Recruiting
NEXT Oncology - Houston	Houston	Texas	Recruiting
NEXT Oncology - Dallas	Irving	Texas	Recruiting
NEXT San Antonio	San Antonio	Texas	Recruiting
Gosford Hospital	Gosford	New South Wales	Recruiting
One Clinical Research - Nedlands	Nedlands	Western Australia	Recruiting
Monash Health	Melbourne	Australia	Recruiting
Princess Margaret Hospital	Toronto	Toronto	Recruiting
The Ottawa Hospital - General Campus	Ottawa	Canada	Recruiting
China-Japan Friendship Hospital	Beijing	Beijing Municipality	Recruiting
The First Affiliated Hospital - Zhejiang University School of Medicine	Hangzhou	Zhejiang	Recruiting
Wenzhou Medical University - The First Affiliated Hospital	Wenzhou	Zhejiang	Recruiting
West China Hospital, Sichuan University	Chengdu	China	Recruiting
Sun Yat-sen University Cancer Center	Guangzhou	China	Recruiting

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