A Study of QLS5133 Monotherapy in Advanced Solid Tumors

Phase 2Not Yet RecruitingNCT07061639

Qilu Pharmaceutical Co., Ltd.212 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

212

Conditions

Advanced Solid Tumors

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Incidence and severity of adverse events and serious adverse events

Incidence and severity of adverse events, serious adverse events, according to NCI-CTCAE Version 5.0

Time frame: up to 2 years

Maximum tolerated dose (MTD)

Highest administered dose with \< 33% participants experiencing dose limiting toxicity (DLT) in the first 6 DLT evaluable participants

Time frame: 28days

Recommended Phase 2 Dose (RP2D)

Based on the maximum tolerated dose, cumulative safety, and pharmacokinetic data

Time frame: up to 2 years

Objective Response Rate (ORR)

Percentage of participants with best response of complete response (CR) or partial response (PR) according to RECIST 1.1

Time frame: up to 2 years

Secondary Outcomes

Maximum Serum Concentration of QLS5133 (Cmax)

PK assessment

Time frame: 21 days

Maximum Serum Concentration of QLS5133 at Steady State (Cmax,ss)

PK assessment

Time frame: 63 days

Minimum Serum Concentration of QLS5133 at Steady State (Cmin,ss)

PK assessment

Time frame: 63 days

Time of Maximum Serum Concentration of QLS5133 (Tmax)

PK assessment

Time frame: 21 days

Terminal Half-life (T1/2) of Serum QLS5133

PK assessment

Time frame: 63 days

Area under the Serum Concentration-Time curve from the time of dosing to the last measurable concentration (AUC0-t) for QLS5133

PK assessment

Time frame: 21 days

Area under the Serum Concentration-Time curve from the time of dosing extrapolated to time infinity (AUC0-∞) for QLS5133

PK assessment

Time frame: 63 days

Apparent Volume of Distribution (Vd) of QLS5133

PK assessment

Time frame: 63 days

Clearance (CL) of QLS5133

PK assessment

Time frame: 63 days

Duration of Response (DOR)

Time from CR or PR to objective disease progression or death to any cause

Time frame: up to 2 years

Progression Free Survival (PFS)

PFS is defined as the time from the start of the treatment until objective disease progression or death from any cause

Time frame: up to 2 years

Time to Progression (TTP)

Time from start of treatment to disease progression

Time frame: 1 years

1 Year Overall Survival (1YOS)

Proportion of participants alive at 1 year from the start of treatment to death from any cause

Time frame: 1 years

2 Year Overall Survival (2YOS)

Proportion of participants alive at 2 years from the start of treatment to death from any cause

Time frame: 2 years

Number of anti-drug antibody (ADA) Positive Participants

Immunogenicity will be measured by the number of participants that are ADA positive

Time frame: up to 2 years

Number of neutralizing antibody (Nab) Positive Participants

Immunogenicity will be measured by the number of participants that are Nab positive

Time frame: up to 2 years

A Study of QLS5133 Monotherapy in Advanced Solid Tumors

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts