Advanced Solid Tumor
Conditions
Keywords
Antibody-drug conjugate
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.
Interventions
DRUGYL201
Patients will be treated with YL201 intravenous (IV) infusion once every 3 weeks (Q3W) as a cycle.
DRUGYL201 and atezolizumab
Patients will be treated with YL201 intravenous (IV) infusion (A mg/kg or B mg/kg, up to 200mg) followed by atezolizumab on day 1 of each 21 day cycle
Sponsors
MediLink Therapeutics (Suzhou) Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 5 months after the last dose of atezolizumab or 6 months after the last dose of YL201, whichever is later. 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 YL201. * Life expectancy of ≥3 months * Able and willing to comply with protocol visits and procedures * Have at least 1 evaluable tumor lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. * Pathologically confirmed diagnosis of an advanced solid tumor (SCLC, mCRPC, ESCC and NSCLC are preferred) for which standard treatment had proven to be ineffective or intolerable, or no standard treatment is available. For ES-SCLC patients in Arm C: no prior anti-cancer treatment
Exclusion criteria
* 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. Received any live vaccine within 4 weeks before the first dose of study drug or intend to receive a live vaccine during the study * 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 (other than alopecia and pigmentation) not yet resolved to NCI CTCAE Grade ≤1, baseline, or the level specified in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the occurrence of DLTs during the first cycle in Part 1 | 21 days of Cycle 1 | — |
| Evaluate the AEs in Part 2 as characterized by type, frequency, severity, timing, seriousness and relationship to study treatment | By the global end of trial date, approximately within 36 months | — |
| Evaluate the prostate-specific antigen (PSA) response rate for patients with prostate cancer in Part 2 | Approximately within 36 months | PSA response rate: defined as the proportion of patients who achieved a ≥50% decrease in PSA from baseline |
| Evaluate the objective response rate (ORR) for patients with solid tumors other than prostate cancer in Part 2, assessed using RECIST version 1.1 | Approximately within 36 months | ORR: defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR). |
| Laboratory abnormalities as characterized by type, frequency, severity, and timing in Part 2 | Biy the end of trial date, approximately within 36 months | — |
| Incidence, nature, and severity of AEs graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V5.0 in Part 3 | Biy the end of trial date, approximately within 36 months | — |
| Nature and frequency of dose-limiting toxicities (DLTs), incidence, nature, and severity of laboratory abnormalities in Part 3 | At the end of cycle 1 (each cycle is 21 days) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess the incidence of anti-YL201 antibodies | Approximately within 36 months | — |
| Evaluate the prostate-specific antigen (PSA) response rate for patients with prostate cancer in Part 1 | Approximately within 36 months | PSA response rate: defined as the proportion of patients who achieved a ≥50% decrease in PSA from baseline |
| Evaluate the PSA progression-free survival (PSA-PFS) for patients with prostate cancer | Approximately within 36 months | PSA-PFS: defined as the time interval from the date of the first dose of study drug to the date of the first documentation of PSA progression, based on PCWG3 criteria. |
| Evaluate the radiological PFS (rPFS) for patients with prostate cancer | Approximately within 36 months | rPFS: defined as the time interval from the date of the first dose of study drug to the date of the first documentation of radiographic tumor progression or death due to any cause, whichever occurs first, based on RECIST 1.1 and PCWG3 criteria. |
| Evaluate the failure-free survival (FFS) for patients with prostate cancer | Approximately within 36 months | FFS: defined as the time interval from the date of the first dose of study drug to the date of the first documentation of radiographic tumor progression, unequivocal clinical progression, PSA progression or death due to disease progression, whichever occurs first. |
| Evaluate the AEs in Part 1 as characterized by type, frequency, severity, timing, seriousness and relationship to study treatment | By the global end of trial date, approximately within 36 months | — |
| Evaluate the disease control rate (DCR) for patients with solid tumors other than prostate cancer, assessed using RECIST version 1.1 | Approximately within 36 months | DCR: defined as the proportion of patients who achieved a best overall response of CR, PR or stable disease (SD). |
| Evaluate the duration of response (DoR) for patients with solid tumors other than prostate cancer, assessed using RECIST version 1.1 | Approximately within 36 months | DoR: defined as the time interval from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of PD. DoR will be assessed for patients with a response (CR or PR) only. |
| Evaluate the time to response (TTR) for patients with solid tumors other than prostate cancer, assessed using RECIST version 1.1 | Approximately within 36 months | TTR: defined as the time interval from the date of the first dose of study drug to the date of the first documentation of objective response (CR or PR). |
| Evaluate the progression-free survival (PFS) for patients with solid tumors other than prostate cancer, assessed using RECIST version 1.1 | Approximately within 36 months | PFS: defined as the time interval from the date of the first dose of study drug to the date of first documentation of PD or death due to any cause, whichever occurs first. |
| Evaluate the overall survival (OS) for patients with solid tumors | Approximately within 36 months | OS: defined as the time interval from the date of the first dose of study drug to the date of death due to any cause. |
| Evaluate the objective response rate (ORR) for patients with solid tumors other than prostate cancer in Part 1, Part 2, and Part 3, assessed using RECIST version 1.1 | Approximately within 36 months | ORR: defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR). |
| Characterize the PK parameter AUC | Approximately within 36 months | — |
| Characterize the PK parameter Cmax | Approximately within 36 months | — |
| Characterize the PK parameter Ctrough | Approximately within 36 months | — |
| Characterize the PK parameter CL | Approximately within 36 months | — |
| Characterize the PK parameter Vd | Approximately within 36 months | — |
| Characterize the PK parameter t1/2 | Approximately within 36 months | — |
Countries
Canada, China, France, Poland, Spain, United States
Contacts
Primary ContactSasha Stann
Backup ContactAlan Xu, Ph.D.
Outcome results
None listed