Clinical trial NCT06384352: A Phase I Study to Evaluate the Safety,Tolerability, Pharmacokinetics, and Efficacy of YL211 in Patients With Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: MediLink Therapeutics (Suzhou) Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Hoffmann-La Roche
First posted: 2024-04-25
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multicenter, open-label, Phase 1 study. The study will enroll subjects with advanced solid tumors. It consists of three parts. Part 1 is dose-escalation part. In part 1, the safety and tolerability of YL211 in patients with selected advanced solid tumors will be evaluated and the MTD and RED will be determined.

Part 2 is backfill enrollment part. We will further estimate the safety and efficacy of YL211 in patients with selected adcance tumor to select the RED(s) of YL211.

Part 3 is dose-expansion part. In this part, we will further evaluate the safety and efficacy of YL211 at the MTD/RED(s) in patients with selected advanced solid tumors YL211 will be administered intravenously (IV) until criteria of treatment discontinuation are met.


Eligibility criteria: 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. History of an advanced solid tumors 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.
5. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
6. Adequate organ and bone marrow function.
7. Have at least 1 extracranial measurable tumor lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Exclusion Criteria:

1. Inadequate washout period for prior anticancer treatment before the first dose of study drug.
2. Uncontrolled or clinically significant cardiovascular and cerebrovascular diseases.
3. Clinically significant concomitant pulmonary disease.
4. Uncontrolled infection that requires systemic therapy within 2 weeks before the first dose.
5. Unresolved toxicities from previous anticancer therapy.
6. A history of severe hypersensitivity reactions to the drug substances, inactive ingredients in the drug product, or other monoclonal antibodies.

Primary outcomes:
measure: To evaluate nature and frequency of AEs of YL211 in patients with advanced solid tumors according to NCI CTCAE version 5.0
timeFrame: Approximately within 36 months
measure: To evaluate nature and frequency of DLTs in part 1.
timeFrame: Approximately within 36 months
measure: ORR assessed using RECIST version 1.1
timeFrame: Approximately within 36 months
measure: To determine the MTD and select the recommended expansion dose(s) (RED(s)) of YL211 in patients with advanced solid tumors
timeFrame: Approximately within 36 months
Secondary outcomes:
measure: To characterize the AUC of YL211 antibody-drug conjugate, YL211 total antibody, unconjugated payload
timeFrame: Approximately within 36 months
measure: To characterize the Cmax of YL211 antibody-drug conjugate, YL211 total antibody, unconjugated payload
timeFrame: Approximately within 36 months
measure: To characterize the Ctrough of YL211 antibody-drug conjugate, YL211 total antibody, unconjugated payload
timeFrame: Approximately within 36 months
measure: To characterize the Tmax of YL211 antibody-drug conjugate, YL211 total antibody, unconjugated payload
timeFrame: Approximately within 36 months
measure: To characterize the CL of YL211 antibody-drug conjugate, YL211 total antibody, unconjugated payload
timeFrame: Approximately within 36 months
measure: To characterize the Vd of YL211 antibody-drug conjugate, YL211 total antibody, unconjugated payload
timeFrame: Approximately within 36 months
measure: To characterize the t1/2 of YL211 antibody-drug conjugate, YL211 total antibody, unconjugated payload
timeFrame: Approximately within 36 months
measure: To evaluate the anti-drug immune response after treatment with YL211
timeFrame: Approximately within 36 months
measure: To evaluate DCR of YL211 in patients with advanced solid tumors using RECIST version 1.1
timeFrame: Approximately within 36 months
measure: To evaluate DoR of YL211 in patients with advanced solid tumors using RECIST version 1.1
timeFrame: Approximately within 36 months
measure: To evaluate SD of YL211 in patients with advanced solid tumors using RECIST version 1.1
timeFrame: Approximately within 36 months
measure: To evaluate TTR of YL211 in patients with advanced solid tumors using RECIST version 1.1
timeFrame: Approximately within 36 months
measure: To evaluate PFS of YL211 in patients with advanced solid tumors using RECIST version 1.1
timeFrame: Approximately within 36 months
measure: To evaluate OS of YL211 in patients with advanced solid tumors using RECIST version 1.1
timeFrame: Approximately within 36 months
measure: To evaluate percent change in target lesion of YL211 in patients with advanced solid tumors using RECIST version 1.1
timeFrame: Approximately within 36 months
Other outcomes:
measure: Characterization of genomic alterations that are predictive of response to YL211
timeFrame: Approximately within 36 months
measure: The use of circulating tumor DNA (ctDNA) to monitor response to YL211 treatment
timeFrame: Approximately within 36 months
Locations:
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavilion
state: Colorado
city: Denver
country: United States
facility: Sarah Cannon Research Institute (SCRI) at HealthONE
state: Colorado
city: North Haven
country: United States
facility: Yale School of Medicine - Yale Cancer Center - Smilow Cancer Hospital Care Centers - North Haven
state: Connecticut
city: Orlando
country: United States
facility: Sarah Cannon Research Institute at Florida Cancer Specialists
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists & Research Institute (FCS) - Sarasota Cattlemen Office
state: Florida
city: Houston
country: United States
facility: The University of Texas - MD Anderson Cancer Center
state: Texas
city: Irving
country: United States
facility: NEXT Oncology - Dallas
state: Texas
city: San Antonio
country: United States
facility: NEXT San Antonio
state: Texas
city: Melbourne
country: Australia
facility: Monash Health
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
city: Toronto
country: Canada
facility: Princess Margaret Hospital
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
Study officials:
References: