Clinical trial NCT05434234: A Study of YL201 in Patients with Advanced Solid Tumors
Official title: A Phase 1, Multicenter, Nonrandomized, Open-Label, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of YL201 in Patients with Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Keywords: Antibody-drug conjugate
Lead sponsor: MediLink Therapeutics (Suzhou) Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-06-27
Enrollment: 196
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a phase 1, multicenter, nonrandomized, open-label, first-in-human study of YL201 conducted in China and the United States. The study will include 2 parts: a dose escalation part (Part 1) followed by a dose expansion part (Part 2).

Part 1 will estimate the MTD/RED(s) in dose escalation cohorts of patients with advanced solid tumors unresponsive to currently available therapies or for whom no standard therapy is available.

Part 2 will include patients with selected advanced solid tumor types enrolled at the MTD/RED(s), to better define the safety profile and evaluate the efficacy of YL201.


Eligibility criteria: Inclusion Criteria:

Common Inclusion Criteria (Part 1 and Part 2)

* Informed of the trial before the start of the trial and voluntarily sign their name and date on the ICF
* Aged ≥18 years
* Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1
* Adequate organ and bone marrow function
* Female patients of childbearing potential must agree to use a highly effective form of contraception and not donate, or retrieve for their own use, ova from the time of screening and throughout the study period, and for at least 6 months after the last dose of study drug. Male patients must agree to use a highly effective form of contraception and not freeze or donate sperm from the time of screening and throughout the study period, and for at least 6 months after the last dose of study drug
* Life expectancy of ≥3 months
* Able and willing to comply with protocol visits and procedures
* Pathologically confirmed diagnosis of an advanced solid tumor for which prior standard treatment had proven to be ineffective or intolerable, or no standard treatment is available

Additional Inclusion Criteria for Part 1

* Have at least 1 evaluable tumor lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Participants with prostate cancer who have bone only disease may be eligible on a case-by-case basis after discussion with the sponsor

Additional Inclusion Criteria for Part 2

* Have at least 1 measurable tumor lesion according to RECIST version 1.1. Participants with prostate cancer who have bone only disease may be eligible on a case-by-case basis after discussion with the sponsor
* Willing to provide archival or fresh tumor tissue samples. Patients who are not able to provide tumor samples or have inadequate samples may be eligible on a case-by-case basis after discussion with the sponsor

Exclusion Criteria:

Common Exclusion Criteria (Part 1 and Part 2)

* Intolerant to prior treatment with a topoisomerase I inhibitor or an ADC that consists of a topoisomerase I inhibitor, including but not limited to topotecan, irinotecan, and Dxd
* Concurrent enrollment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study
* Prior systemic anticancer treatment including chemotherapy, molecular targeted therapy, hormonal therapy, immunotherapy, or biological therapy within 3 weeks before the first dose of study drug (use of oral fluorouracil \[eg, tegafur and capecitabine\] or small molecular targeted therapy within 2 weeks or 5 half-life periods \[whichever is shorter\] before the first dose; use of mitomycin or nitrosoureas within 6 weeks before the first dose; use of herbal medicine with antitumor indications or nonspecific immunomodulators \[eg, thymosin, interferon, and interleukin\] within 2 weeks before the first dose)
* Prior radiation therapy, including palliative stereotactic radiation with abdominal, within 4 weeks before the first dose of study drug (if palliative stereotactic radiation therapy without abdominal, within 2 weeks)
* Undergone major surgery (not including diagnostic surgery) within 4 weeks before the first dose of study drug or expect major surgery during the study
* Undergone allogeneic hematopoietic stem cell transplantation (HSCT) before the first dose of study drug, or autologous HSCT within 3 months before the first dose of study drug
* Received systemic steroids (\>10 mg/day of prednisone or its equivalent) or other immunosuppressive therapy within 2 weeks before the first dose of study drug. The following are exceptions to this criterion:

  1. Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection)
  2. Systemic steroids at physiological doses as replacement therapy (eg, physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency)
  3. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
* Received any live vaccine within 4 weeks before the first dose of study drug or intend to receive a live vaccine during the study
* A history of leptomeningeal carcinomatosis
* Brain metastases or spinal cord compression unless asymptomatic or treated and stable off steroids and anti-convulsants for at least 2 weeks before the first dose of study drug
* Uncontrolled or clinically significant cardiovascular disease
* A history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that requires steroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
* Clinically significant concomitant pulmonary disease
* Have a diagnosis of Gilbert's syndrome
* Uncontrolled third-space fluid that requires repeated drainage
* Active gastric and duodenal ulcers, ulcerative colitis, or other gastrointestinal conditions that may cause bleeding or perforation by the investigator's discretion
* Uncontrolled infection that requires systemic therapy within 1 week before the first dose
* Known human immunodeficiency virus (HIV) infection
* Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Active HBV is defined as hepatitis B core antibody (HBcAb) or hepatitis B surface antigen (HBsAg) positive, and HBV DNA level above ULN at the study site; active HCV is defined as positive hepatitis C antibody and HCV RNA level above ULN at the study site
* Unresolved toxicities from previous anticancer therapy, defined as toxicities not yet resolved to NCI CTCAE Grade ≤1, baseline, or the level specified in the inclusion/exclusion criteria with the exception of alopecia (any grade), pigmentation (any grade), and peripheral neuropathy (Grade ≤2). Patients with irreversible toxicity (eg, hearing loss) that is reasonably not expected to be aggravated by the study drug can be enrolled after discussion with the sponsor
* A history of severe hypersensitivity reactions to the drug substances, inactive ingredients in the drug product, or other mAbs
* Women who are breastfeeding or pregnant as confirmed by pregnancy tests performed within 7 days before the first dose
* Any illness, medical condition, organ system dysfunction, or social situation, including but not limited to mental illness or substance/alcohol abuse, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, adversely affect the patient's ability to cooperate and participate in the study, or compromise the interpretation of study results Additional Exclusion Criteria for Part 2
* Multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other curatively treated solid tumors

Primary outcomes:
measure: Evaluate the occurrence of DLTs during the first cycle in Part 1
timeFrame: 21 days of Cycle 1
measure: Evaluate the AEs in Part 2 as characterized by type, frequency, severity, timing, seriousness and relationship to study treatment
timeFrame: By the global end of trial date, approximately within 36 months
measure: Evaluate the prostate-specific antigen (PSA) response rate for patients with prostate cancer in Part 2
timeFrame: Approximately within 36 months
measure: Evaluate the objective response rate (ORR) for patients with solid tumors other than prostate cancer in Part 2, assessed using RECIST version 1.1
timeFrame: Approximately within 36 months
Secondary outcomes:
measure: Evaluate the AEs in Part 1 as characterized by type, frequency, severity, timing, seriousness and relationship to study treatment
timeFrame: By the global end of trial date, approximately within 36 months
measure: Characterize the PK parameter AUC
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter Cmax
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter Ctrough
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter CL
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter Vd
timeFrame: Approximately within 36 months
measure: Characterize the PK parameter t1/2
timeFrame: Approximately within 36 months
measure: Assess the incidence of anti-YL201 antibodies
timeFrame: Approximately within 36 months
measure: Evaluate the prostate-specific antigen (PSA) response rate for patients with prostate cancer in Part 1
timeFrame: Approximately within 36 months
measure: Evaluate the PSA progression-free survival (PSA-PFS) for patients with prostate cancer
timeFrame: Approximately within 36 months
measure: Evaluate the radiological PFS (rPFS) for patients with prostate cancer
timeFrame: Approximately within 36 months
measure: Evaluate the failure-free survival (FFS) for patients with prostate cancer
timeFrame: Approximately within 36 months
measure: Evaluate the objective response rate (ORR) for patients with solid tumors other than prostate cancer in Part 1, assessed using RECIST version 1.1
timeFrame: Approximately within 36 months
measure: Evaluate the disease control rate (DCR) for patients with solid tumors other than prostate cancer, assessed using RECIST version 1.1
timeFrame: Approximately within 36 months
measure: Evaluate the duration of response (DoR) for patients with solid tumors other than prostate cancer, assessed using RECIST version 1.1
timeFrame: Approximately within 36 months
measure: Evaluate the time to response (TTR) for patients with solid tumors other than prostate cancer, assessed using RECIST version 1.1
timeFrame: Approximately within 36 months
measure: Evaluate the progression-free survival (PFS) for patients with solid tumors other than prostate cancer, assessed using RECIST version 1.1
timeFrame: Approximately within 36 months
measure: Evaluate the overall survival (OS) for patients with solid tumors
timeFrame: Approximately within 36 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University California San Diego Moores Cancer Center
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Port St. Lucie
country: United States
facility: Hematology Oncology Associates of the Treasure Coast
state: Florida
city: Indianapolis
country: United States
facility: Community Health Network
state: Indiana
city: Boston
country: United States
facility: Mass General Cancer Center: Hematology
state: Massachusetts
city: Detroit
country: United States
facility: University of Michigan - Rogel Cancer Center - Urology Oncology Clinic
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: St Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Santa Fe
country: United States
facility: CHRISTUS St. Vincent Health System - CHRISTUS St. Vincent Regional Cancer Center (Andrea Teague)
state: New Mexico
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Dallas
country: United States
facility: NEXT Oncology-Dallas
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: San Antonio
country: United States
facility: NEXT San Antonio
state: Texas
city: Tyler
country: United States
facility: UT Health East Texas HOPE Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute - Inova Fairfax Hospital Location
state: Virginia
city: Spokane
country: United States
facility: Medical Oncology Associates and Summit Cancer Centers
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Edmonton
country: Canada
facility: Cross Cancer Institute - Alberta Health Services; Siu Chung Chu Professional Corporation
state: Alberta
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Bordeaux
country: France
facility: CHU de Bordeaux - Hopital Saint Andre
city: Dijon
country: France
facility: Centre Georges-Francois Leclerc
city: Marseille
country: France
facility: APHM - Hopital Nord
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: Institut Curie - Site Paris
city: Poitiers
country: France
facility: CHU de Poitiers
city: Saint-Herblain
country: France
facility: Institut de cancerologie de l'Ouest - Site Saint Herblain
city: Suresnes
country: France
facility: Hopital Foch
city: Otwock
country: Poland
facility: Europejskie Centrum Zdrowia Otwock Sp. z.o.o.
city: Poznan
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Poznaniu
city: Leganes
country: Spain
facility: Hospital Universitario Severo Ochoa
state: Madrid
city: Moncloa-Aravaca
country: Spain
facility: START Madrid - Hospital Universitario Fundacion Jimenez Diaz
state: Madrid
city: Pozuelo de Alarcon
country: Spain
facility: NEXT Oncology Madrid
state: Madrid
city: Usera
country: Spain
facility: Hospital Universitario 12 de Octubre
state: Madrid
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: NEXT Oncology. Phase I Unit / IOB - Hospital Quironsalud Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: START Madrid - Centro Integral Oncologico Clara Campal (CIOCC) - Hospital Universitario HM Sanchinarro
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
Study officials:
References: