Advanced Solid Tumors
Conditions
Brief summary
The Phase 1 trial includes Phase 1a (dose-escalation) and Phase 1b (dose-expansion): * Phase 1a: Assesses safety, tolerability, PK, and preliminary efficacy of QLS5132 in advanced solid tumors using ATD + BOIN, given IV every 3 weeks. Up to 12 subjects may be enrolled in promising dose levels. * Phase 1b: Evaluates QLS5132's anti-tumor efficacy in specific CLDN6-positive solid tumors, including ovarian cancer, NSCLC, gastric cancer, and others. Expansion studies at 1\ 3 selected dose levels follow successful Phase 1a results.
Interventions
DRUGQLS5132
antibody drug conjugate (ADC).
Sponsors
Qilu Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Advanced solid tumors; * Measurable disease, per RECIST v1.1; * Eastern Cooperative Oncology Group (ECOG) performance status 0-1; * 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;
Exclusion criteria
* Previous treatment with drugs targeting CLDN6 (including ADCs), or any drug containing topoisomerase I inhibitors (including ADCs); * Received prior chemotherapeutic, investigational, or other therapies for the treatment of cancer within 2 weeks with small molecule and within 4 weeks with biologic before the first dose of QLS5132; * Progressive or symptomatic brain metastases; * Serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection; * History of significant cardiac disease, or poorly controlled diabetes mellitus; * History of recurrent autoimmune diseases; * History of myelodysplastic syndrome (MDS) or 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 QLS5132 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time of Maximum Serum Concentration of QLS5132 (Tmax) | 21 days | PK assessment |
| Terminal Half-life (T1/2) of Serum QLS5132 | 63 days | PK assessment |
| Area under the Serum Concentration-Time curve from the time of dosing to the last measurable concentration (AUC0-t) for QLS5132 | 21 days | PK assessment |
| Area under the Serum Concentration-Time curve from the time of dosing extrapolated to time infinity (AUC0-∞) for QLS5132 | 63 days | PK assessment |
| Volume of Distribution (Vd) of QLS5132 | 63 days | PK assessment |
| Clearance (CL) of QLS5132 | 63 days | PK assessment |
| 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 |
| Maximum Serum Concentration of QLS5132 (Cmax) | 21 days | PK assessment |
| 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 |
| Time to Progression (TTP) | 1 years | Time from start of treatment to disease progression |
| 1 Year Overall Survival (1YOS) | up to 2 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 |
| 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 QLS5132 at Steady State (Cmax,ss) | 63 days | PK assessment |
| Minimum Serum Concentration of QLS5132 at Steady State (Cmin,ss) | 63 days | PK assessment |
Countries
China
Contacts
Primary ContactTao Zhu, PhD
Backup ContactZhengbo Song, PhD
Outcome results
None listed