Advanced Solid Tumors
Conditions
Brief summary
The phase 1/2 clinical study includes three stages: Phase 1 dose escalation, phase 1 PK expansion and phase 2 cohort expansion： * Phase 1: Assesse safety, tolerability, PK, immunogenicity and preliminary efficacy of QLS5133 in advanced solid tumors. Phase 1 dose escalation will use ATD + BOIN, the maximum sample size for each dose group is 12. For Phase 1 PK expansion, 1 to 4 appropriate doses will be selected. After the DLT observation period in the selected dose group up to 12 subjects (including those subjects in the dose escalation stage) can be further enrolled for PK expansion. * Phase 2: Evaluates QLS5133's anti-tumor efficacy in subjects with advanced solid tumors. at least 2 dose groups will be expanded.
Interventions
DRUGQLS5133
antibody drug conjugate (ADC)
Sponsors
Qilu Pharmaceutical 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
* Aged ≥ 18 years on the day of signing the ICF, male or female; * Eastern Cooperative Oncology Group (ECOG) performance status (PS) score: 0 or 1; * Measurable disease, per RECIST v1.1; * Adequate organ function; * Recover from all reversible AEs from previous anti-tumor treatment (i.e., Grade ≤ 1, according to NCI-CTCAE v5.0), excluding alopecia (any grade) and Grade ≤ 2 neuropathy peripheral, or who experience other abnormalities that are not clinically significant or toxicities judged to have no risk by the investigator; * Left ventricular ejection fraction (LVEF) ≥ 50%;
Exclusion criteria
* Previous treatment with drugs targeting CDH6 (including ADCs), or any drug containing topoisomerase I inhibitors (including ADCs); * Large and uncontrollable pleural, pericardial or abdominal effusion before the first dose (those who are stable for at least 2 weeks after drainage can be enrolled); * Progressive or symptomatic brain metastases; * Clinically significant bleeding symptoms or obvious bleeding tendency within 1 month before the first dose * History of significant cardiac disease, or poorly controlled diabetes mellitus; * History of recurrent autoimmune diseases; * History of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML); * History of other active malignant tumors within 3 years before signing the informed consent form; * If female, is pregnant or breastfeeding; * Be allergic to any component of QLS5133 or its excipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of adverse events and serious adverse events | up to 2 years | Incidence and severity of adverse events, serious adverse events, according to NCI-CTCAE Version 5.0 |
| Maximum tolerated dose (MTD) | 28days | Highest administered dose with \< 33% participants experiencing dose limiting toxicity (DLT) in the first 6 DLT evaluable participants |
| Recommended Phase 2 Dose (RP2D) | up to 2 years | Based on the maximum tolerated dose, cumulative safety, and pharmacokinetic data |
| Objective Response Rate (ORR) | up to 2 years | Percentage of participants with best response of complete response (CR) or partial response (PR) according to RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Terminal Half-life (T1/2) of Serum QLS5133 | 63 days | PK assessment |
| Area under the Serum Concentration-Time curve from the time of dosing to the last measurable concentration (AUC0-t) for QLS5133 | 21 days | PK assessment |
| Area under the Serum Concentration-Time curve from the time of dosing extrapolated to time infinity (AUC0-∞) for QLS5133 | 63 days | PK assessment |
| Apparent Volume of Distribution (Vd) of QLS5133 | 63 days | PK assessment |
| Clearance (CL) of QLS5133 | 63 days | PK assessment |
| Duration of Response (DOR) | up to 2 years | Time from CR or PR to objective disease progression or death to any cause |
| Maximum Serum Concentration of QLS5133 (Cmax) | 21 days | PK assessment |
| Time to Progression (TTP) | 1 years | Time from start of treatment to disease progression |
| 1 Year Overall Survival (1YOS) | 1 years | Proportion of participants alive at 1 year from the start of treatment to death from any cause |
| 2 Year Overall Survival (2YOS) | 2 years | Proportion of participants alive at 2 years from the start of treatment to death from any cause |
| Number of anti-drug antibody (ADA) Positive Participants | up to 2 years | Immunogenicity will be measured by the number of participants that are ADA positive |
| Number of neutralizing antibody (Nab) Positive Participants | up to 2 years | Immunogenicity will be measured by the number of participants that are Nab positive |
| Progression Free Survival (PFS) | up to 2 years | PFS is defined as the time from the start of the treatment until objective disease progression or death from any cause |
| Maximum Serum Concentration of QLS5133 at Steady State (Cmax,ss) | 63 days | PK assessment |
| Minimum Serum Concentration of QLS5133 at Steady State (Cmin,ss) | 63 days | PK assessment |
| Time of Maximum Serum Concentration of QLS5133 (Tmax) | 21 days | PK assessment |
Countries
China
Contacts
Primary ContactXiaohua Wu, PhD
Outcome results
None listed