A Study of QLS31905 Combination Chemotherapy as First-Line Treatment in Patients With Advanced Solid Tumors

Sponsor

Qilu Pharmaceutical Co., Ltd. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06041035

Collaborator

(none)

115

Enrollment

Location

Arms

Anticipated Duration (Months)

4.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study aims to evaluate the efficacy and safety of QLS31905 plus chemotherapy in patients with Claudin18.2-positive advanced solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor	Drug: QLS31905 Drug: Nab paclitaxel Drug: Gemcitabine Drug: Oxaliplatin Drug: Capecitabine Drug: Cisplatin	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

115 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase IB/II Clinical Study to Assess the Efficacy and Safety of QLS31905 in Combination With Chemotherapy as First-line Treatment in Patients With Claudin 18.2 (CLDN18.2) Positive Advanced Malignant Solid Tumors

Anticipated Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Oct 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: QLS31905 + nab-paclitaxel + gemcitabine (Part A/B) Pancreatic cancer participants will be treated with QLS31905 in combination with nab-paclitaxel and gemcitabine for part A of the study to establish the recommended dose of QLS31905 for part B. In part B, the participants will be treated with QLS31905 at a dose determined by the part A of the study in combination with nab-paclitaxel and gemcitabine.	Drug: QLS31905 Administered as an intravenous infusion. Drug: Nab paclitaxel 125 mg/m2 administered as IV infusion on D1/D8/D15 of each cycle. Drug: Gemcitabine 1000 mg/m2 administered as IV infusion on D1/D8/D15 of each cycle.
Experimental: QLS31905 + oxaliplatin + capecitabine (Part B) In part B, gastric/gastroesophageal junction cancer participants will be treated with QLS31905 at dose determined by part A of the study in combination with oxaliplatin and capecitabine.	Drug: QLS31905 Administered as an intravenous infusion. Drug: Oxaliplatin 85 mg/m2, intravenous infusion, D1/D15, up to 6 cycles. Drug: Capecitabine 1000 mg/m2, oral, bid, D1-D7,D15-D21, up to 6 cycles.
Experimental: QLS31905 + gemcitabine+cisplatin(Part B) In part B, other solid tumor participants including but not limited to biliary tract cancer will be treated with QLS31905 at dose determined by part A in combination with standard chemotherapy recommended by guidelines.QLS31905 plus gemcitabine+ cisplatin as the first-line treatment of advanced biliary tract cancer.	Drug: QLS31905 Administered as an intravenous infusion. Drug: Gemcitabine 1000 mg/m2 administered as IV infusion on D1/D8/D15 of each cycle. Drug: Cisplatin 25 mg/m2, intravenous infusion, D1/D15, up to 6 cycles.

Arm

Intervention/Treatment

Experimental: QLS31905 + nab-paclitaxel + gemcitabine (Part A/B)

Pancreatic cancer participants will be treated with QLS31905 in combination with nab-paclitaxel and gemcitabine for part A of the study to establish the recommended dose of QLS31905 for part B. In part B, the participants will be treated with QLS31905 at a dose determined by the part A of the study in combination with nab-paclitaxel and gemcitabine.

Drug: QLS31905

Administered as an intravenous infusion.

Drug: Nab paclitaxel

125 mg/m2 administered as IV infusion on D1/D8/D15 of each cycle.

Drug: Gemcitabine

1000 mg/m2 administered as IV infusion on D1/D8/D15 of each cycle.

Experimental: QLS31905 + oxaliplatin + capecitabine (Part B)

In part B, gastric/gastroesophageal junction cancer participants will be treated with QLS31905 at dose determined by part A of the study in combination with oxaliplatin and capecitabine.

Drug: QLS31905

Administered as an intravenous infusion.

Drug: Oxaliplatin

85 mg/m2, intravenous infusion, D1/D15, up to 6 cycles.

Drug: Capecitabine

1000 mg/m2, oral, bid, D1-D7,D15-D21, up to 6 cycles.

Experimental: QLS31905 + gemcitabine+cisplatin(Part B)

In part B, other solid tumor participants including but not limited to biliary tract cancer will be treated with QLS31905 at dose determined by part A in combination with standard chemotherapy recommended by guidelines.QLS31905 plus gemcitabine+ cisplatin as the first-line treatment of advanced biliary tract cancer.

Drug: QLS31905

Administered as an intravenous infusion.

Drug: Gemcitabine

1000 mg/m2 administered as IV infusion on D1/D8/D15 of each cycle.

Drug: Cisplatin

25 mg/m2, intravenous infusion, D1/D15, up to 6 cycles.

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose (MTD) (Part A) [Approximately 12 months]
As measured by number of participants experiencing dose related toxicity (DLT) in each escalating cohort.
Phase 2 Recommended Dose（RP2D)(Part A) [Approximately 12 months]
Monitor for MTD, and minimal efficacious dose by monitoring responses at different dose levels.
Objective response rate (ORR)(Part B) [Approximately 12 months]
ORR is defined as the proportion of participants who have a best overall response of Complete Response (CR) or Partial Response (PR) as assessed by investigator evaluation per RECIST 1.1.

Secondary Outcome Measures

Safety assessed by Adverse Events (AEs) [Approximately 12 months]
An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom,or disease (new or exacerbated) temporally associated with the use of a medicinal product.
Safety assessed by incidence of serious adverse events (SAE) [Approximately 12 months]
Adverse Event (AE) is considered "serious" if the investigator or sponsor view any of the following outcomes: Death, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect,hospitalization, or medically important event.
Number of participants with laboratory value abnormalities and/or adverse events (AEs) [Approximately 12 months]
Number of participants with potentially clinically significant laboratory values.
Progression Free Survival(PFS) [Approximately 12 months]
PFS is defined as the duration from the subject's first dose of the investigational product to the first imaging confirmation of progressive disease per RECIST 1.1 by investigator evaluation or death due to any cause (whichever occurs first).
Duration Of Response (DOR) [Approximately 12 months]
DOR is defined as the time from the date of the first response (CR/PR) until the date of progressive disease as assessed by investigator evaluation per RECIST 1.1 or death due to any cause (whichever occurs first).
Overall Survival (OS) [Approximately 12 months]
OS is defined as the duration from the first dose of the investigational product to the time point when death occurs due to any cause.
Pharmacokinetics(PK) of QLS31905: Maximum concentration (Cmax) [Approximately 12 months]
Cmax will be derived from the PK serum samples collected.
PK of QLS31905: Time of the maximum concentration (Tmax) [Approximately 12 months]
Tmax will be derived from the PK serum samples collected.
PK of QLS31905: Terminal elimination half-life (T1/2) [Approximately 12 months]
T1/2 will be derived from the PK serum samples collected.
PK of QLS31905: Clearance (CL) [Approximately 12 months]
CL will be derived from the PK serum samples collected.
PK of QLS31905: Apparent volume of distribution during the terminal phase (Vz) [Approximately 12 months]
Vz will be derived from the PK serum samples collected.
Number of anti-drug antibody (ADA) Positive Participants [Approximately 12 months]
Immunogenicity will be measured by the number of participants that are ADA positive.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects voluntarily participate in the study and sign the informed consent form;
Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
Expected survival time ≥ 3 months;
Histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumors;
No prior systemic anti-tumor treatment for locally advanced unresectable or metastatic disease;
Tumor tissue samples determined to have moderate-to-high Claudin18.2 expression by immunohistochemistry (IHC);
At least one measurable lesion per RECIST v1.1;
Patients with adequate cardiac, liver, renal function, etc.

Exclusion Criteria:

History of malignancies other than the target cancer within 5 years prior to the first dose of the investigational product ;
Underwent major organ surgery (excluding needle biopsy) or had significant trauma within 28 days prior to enrollment, or requires elective surgery during the study;
Known central nervous system metastases;
Patients with hepatitis B; patients with hepatitis C; patients who test positive for syphilis, or patients with a known history of HIV or positive HIV screening test;
Patients with a known history of psychoactive drug abuse, alcohol abuse, or substance abuse;
Patients with added risks associated with the study or may interfere with the interpretation of study results as determined by the investigator, or deemed unsuitable by the investigator and/or sponsor.