Clinical trial NCT05461287: Safety, Tolerability and Pharmacokinetics Study of QLS31904 in Patients With Advanced Solid Tumors
Official title: An Open-label, Phase 1 Study of QLS31904 as Monotherapy to Assess the Safety, Tolerability and PK in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: Qilu Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-07-18
Enrollment: 290
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open label, phase 1 clinical study to evaluate the safety, tolerability, dose limiting toxicities (DLTs), maximum tolerated dose (MTD) or maximum administered dose (MAD) and recommended phase 2 dose (RP2D) of QLS31904 q2w/q3w intravenous use in patients with advanced solid tumors. Additional objectives are to characterise pharmacokinetics and pharmacodynamics, and to evaluate efficacy signals. This study is consisted of phase Ia (Dose Escalation) and phase Ib (Dose Expansion). Phase Ib will further explore QLS31904 in selected patients populations based on data from phase Ia. The Phase Ib objectives, endpoints and design will be specified in a study protocol amendment after availability of phase Ia results.


Eligibility criteria: Inclusion Criteria:

1. Understanding and voluntarily signing the informed consent form;
2. Male or female, age≥18 years;
3. Patients with histologically or cytologically confirmed advanced solid tumors including small cell lung cancer, small cell cancers in other organs or neuroendocrine carcinoma who have progression after on theor intolerance to standard of care, or have no effective standard therapeutic regimen;
4. Tumours must be confirmed expression of DLL3.
5. Presence of at least one measurable lesion meeting the requirements in RECIST v1.1 evaluation criteria;
6. ECOG PS score: 0\~1;
7. Patients with life expectancy ≥3 months;
8. Adequate organ function as defined in protocol. Futher inclusion criteria apply.

Exclusion Criteria:

1. Having received the treatment targeting CD3 or DLL3 previously;
2. Receiving any systematic antitumor therapy or other investigational product within 4 weeks prior to the first dose of QLS31904;
3. Receiving radiotherapy within 2 weeks prior to the first dose of QLS31904;
4. For the dose-escalation, participants who experienced severe immune-mediated AEs while on treatment with Immune checkpoint inhibitors (e.g., anti PD-L1, anti PD-1, anti CTLA-4) ;
5. Symptomatic central nervous system (CNS) metastasis.
6. History of concurrent serious cerebro- and cardiovascular diseases including but not limited to: unstable angina pectoris, myocardial infarction, cerebrovascular accident or transient ischemic attack within 6 months prior to the first doses, poorly controlled hypertension or arrhythmia, or any other arterial thrombosis or embolic event;
7. History of concurrent gastrointestinal diseases including but not limited to: gastrointestinal bleeding or perforation, acute pancreatitis;
8. History of concurrent lung damage including but not limited to: interstitial lung disease, other diseases requiring oxygen inhalation.
9. Presence of active pneumonia or history of noninfectious pneumonia;
10. Active infection requiring systematic treatment/antibiotics or intravenous use of systemic anti-infection therapy with one week prior to the first dose or use for more than 7 days;
11. Known positive for human immunodeficiency virus (HIV); Having evidence on infection of hepatitis C virus (HCV) or syphilis; Hepatitis B virus (HBV) infected individuals with positive HBsAg and HBV DNA copy \>1000 IU/ml or 200 cps/mL; Following treatment according to guidelines, previously HBV infected individuals in screening period can be enrolled only;
12. Presence of active or suspicious autoimmune disease.
13. Previous allogeneic bone marrow transplantation or solid organ transplantation;
14. Major surgery (judged by investigators) or in the recovery period of the surgery within 4 weeks before the first dose of QLS31904.
15. Vaccination of live attenuated vaccine within 4 weeks prior to the first dose of QLS31904;
16. Having other malignant tumor other than the disease investigated within 2 years prior to the ICF;
17. Known allergy to any component of QLS31904;
18. Any other disease or condition of clinical significance that can affect the compliance with the protocol (e.g., history of psychosis or drug abuse), affect the signature of the informed consent form (e.g., drug addiction and drug abuse);
19. Any condition is unsuitable to be involved in this clinical trial, as considered by investigators.

Primary outcomes:
measure: DLT
timeFrame: Up to 28 approximately days
measure: MTD
timeFrame: Up to 24 approximately months
measure: RP2D
timeFrame: Up to 24 approximately months
Secondary outcomes:
measure: Incidence of adverse event (AE)
timeFrame: Up to 24 approximately months
measure: Severity of adverse event (AE)
timeFrame: Up to 24 approximately months
measure: Incidence of serious adverse event (SAE)
timeFrame: Up to 24 approximately months
measure: Severity of serious adverse event (SAE)
timeFrame: Up to 24 approximately months
measure: Incidence of immune related adverse event (irAE)
timeFrame: Up to 24 approximately months
measure: Incidence of clinically significant laboratory examination and abnormal changes in other examinations
timeFrame: Up to 24 approximately months
measure: peak concentration (Cmax)
timeFrame: Up to 24 approximately months
measure: time to peak (Tmax)
timeFrame: Up to 24 approximately months
measure: trough concentration (Ctrough)
timeFrame: Up to 24 approximately months
measure: area under the plasma drug concentration-time curve (AUC0-t )
timeFrame: Up to 24 approximately months
measure: area under the plasma drug concentration-time curve (AUC0-inf)
timeFrame: Up to 24 approximately months
measure: volume of distribution (Vss)
timeFrame: Up to 24 approximately months
measure: elimination half-life (t1/2)
timeFrame: Up to 24 approximately months
measure: clearance rate (CL)
timeFrame: Up to 24 approximately months
measure: mean retention time (MRT)
timeFrame: Up to 24 approximately months
measure: ORR
timeFrame: Up to 24 approximately months
measure: DOR
timeFrame: Up to 24 approximately months
measure: DCR
timeFrame: Up to 24 approximately months
measure: PFS/PFS6
timeFrame: Up to 24 approximately months
measure: OS
timeFrame: Up to 24 approximately months
measure: ADA
timeFrame: Up to 24 approximately months
measure: Nab
timeFrame: Up to 24 approximately months
Other outcomes:
measure: DLL3 expression in tumor tissue
timeFrame: Up to 24 approximately months
measure: Objective response based on iRECIST criteria in patients with measurable disease
timeFrame: Up to 24 approximately months
Locations:
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
Study officials:
References: