A Study of QL1604 Plus Nab-paclitaxel Versus Paclitaxel in Subjects With Advanced Gastric Cancer.

A Study of QL1604 Plus Nab-paclitaxel Versus Paclitaxel for Participants With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma That Progressed After Therapy With Platinum and Fluoropyrimidine

This is a study for participants with advanced gastric or gastroesophageal junction adenocarcinoma who had tumor progression after first-line treatment with platinum and fluoropyrimidine doublet therapy. The study will be conducted in 2 parts.

Study Overview

• Status: Unknown
• Conditions: Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: QL1604; Drug: Nab-paclitaxel; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Anticipated): 492
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 2000 32
      • Fudan University Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Volunteer to participate in this clinical study; Completely understand and know this study as well as sign the informed consent form (ICF);
2. Age ≥ 18 years and ≤ 80 years when ICF is signed;
3. Have histologically or cytologically confirmed diagnosis of locally advanced, unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma(G/GEJC).
4. Eastern Cooperative Oncology Group performance status of 0 or 1;
5. Life expectancy of at least 12 weeks;
6. Have measurable disease as defined by RECIST 1.1 as determined by the investigator;
7. Be willing to provide newly-obtained or paraffin-embedded tissue for PD-L1 and other biomarker analysis;
8. HER-2/neu negative；
9. Female subjects of childbearing potential should have a negative serum human chorionic gonadotropin(HCG) test within 7 days prior to receiving the first dose of study medication and are not breastfeeding;
10. Male and female subjects able to have children must agree to use highly effective method of contraception throughout the study and for at least 180 days after last dose.

Exclusion Criteria:

1. Has non-G/GEJC such as squamous cell carcinoma, adenosquamous carcinoma, undifferentiated gastric cancer;
2. Known allergy or hypersensitivity to QL1604/nab-paclitaxel/paclitaxel or any components used in the preparation;
3. Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease disease-relieving drugs, corticosteroids or immunosuppressant）;
4. Has a diagnosis of immunodeficiency or received systemic steroid therapy （>10mg daily of prednisone or equivalent drug）or any other form of immunosuppressive therapy within 14 days prior to the planned start of study therapy；
5. Subjects who have received radiotherapy, chemotherapy, monoclonal antibodies,targeted therapy, other anti-tumor treatments,or participating in other clinical studies is less than 4 weeks before the first dose of trial treatment;
6. Has a known additional malignancy that is progressing or requires active treatment in past 3 years;
7. Subjects with known central nervous system (CNS) metastasis;
8. Has a history of pneumonitis that required steroids in past 3 years;
9. Has an active infection requiring systemic therapy；
10. Subjects with the history of Human Immunodeficiency Virus (HIV)、acquired, congenital immunodeficiency diseases、organ transplant;
11. Has hepatitis B surface antigen (HBsAg) positive and/or hepatitis B core antibody (HBcAb) positive and HBV deoxyribonucleic acid (HBV DNA) >1000 copies/mL, or hepatitis C virus antibody positive;
12. Has received a live vaccine within 30 days of the planned start of study therapy；
13. Has received prior immune checkpoint inhibitors;
14. Known psychiatric or substance abuse disorders that would interfere with the requirements of the study;
15. Subjects with uncontrollable cardiac diseases;
16. Has accompanying diseases that seriously endanger the subject's safety or affect the study by the investigator;
17. Has any condition that increases the risk, interferes with the study results by the investigator, or investigators/sponsor consider the subjects are not suitable for this trial;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Cohort A; Participants receive QL1604 and nab-paclitaxel on Days 1, 8, and 15 of each 28-day cycle. If not disease progression after 4 cycles, participants receive QL1604 monotherapy until disease progression、unacceptable toxicity or up to 2 years.	Drug: QL1604; 3mg/kg, D1,8,15,Q4w, IV infusion; Drug: Nab-paclitaxel; 100mg/m2, D1,8,15,Q4w, IV infusion
Experimental: Experimental: Cohort B-arm1; Participants receive QL1604 and nab-paclitaxel on Days 1, 8, and 15 of each 28-day cycle. If not disease progression after 4 cycles, participants receive QL1604 monotherapy until disease progression、unacceptable toxicity or up to 2 years.	Drug: QL1604; 3mg/kg, D1,8,15,Q4w, IV infusion; Drug: Nab-paclitaxel; 100mg/m2, D1,8,15,Q4w, IV infusion
Experimental: Experimental: Cohort B-arm2; Participants receive paclitaxel on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.	Drug: Paclitaxel; 80mg/m2, D1,8,15,Q4w, IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence and severity of adverse events (AE) and serious adverse events (SAE) according to CTCAE V5.0	Safety and tolerability (stage 1)	Up to 90 days from last dose
The percentages of participants discontinuing or suspending the study drug due to an AE.	Safety and tolerability (stage 1)	Up to 90 days from last dose
Overall survival（OS）（stage 2）	Overall survival is defined as time from randomization to death due to any cause.	from the date of first dose until the date of death from any cause,assessed up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate（ORR）assessed by the investigators according to RECIST 1.1（stage 1 and 2）	Objective response rate（ORR）assessed by the investigators according to RECIST 1.1.	up to 2 years
Disease control rate（DCR）assessed by the investigators according to RECIST 1.1（stage 1 and 2）	Disease control rate（DCR）assessed by the investigators according to RECIST 1.1.	up to 2 years
Progression-free survival（PFS）assessed by the investigators according to RECIST 1.1（stage 1 and 2）	Progression-free survival（PFS）assessed by the investigators according to RECIST 1.1.	up to 2 years
Tumor response rate（TRR）assessed by the investigators according to RECIST 1.1（stage 1 and 2）	Tumor response rate（TRR）assessed by the investigators according to RECIST 1.1.	up to 2 years
Overall survival(stage 1)	Overall survival is defined as time from randomization to death due to any cause.	from the date of first dose until the date of death from any cause,assessed up to 2 years
Area under the concentration-time curve (AUC ) following single dose administration of PD-1（stage 1 ）	Area under the concentration-time curve (AUC ) following single dose administration of PD-1	through study completion, an average of 2 years
Peak plasma concentration (Cmax) following single dose administration of PD-1（stage 1 ）	Peak plasma concentration (Cmax) following single dose administration of PD-1	through study completion, an average of 2 years
Steady-state trough serum concentration of multiple Dose Administration of PD-1（stage 2）	Steady-state trough serum concentrationof multiple Dose Administration of PD-1	through study completion, an average of 2 years
Steady-state peak serum concentration of multiple Dose Administration of PD-1（stage 2）	Steady-state peak serum concentration of multiple Dose Administration of PD-1	through study completion, an average of 2 years
Immunogenicity（stage 1 and 2）	The titer of anti-drug antibodies (ADA)and neutralizing antibodies(Nab).	through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Qilu Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2020
• Primary Completion (Anticipated): April 30, 2022
• Study Completion (Anticipated): November 30, 2022

Study Registration Dates

• First Submitted: June 10, 2020
• First Submitted That Met QC Criteria: June 15, 2020
• First Posted (Actual): June 17, 2020

Study Record Updates

• Last Update Posted (Actual): June 17, 2020
• Last Update Submitted That Met QC Criteria: June 15, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Adenocarcinoma; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Albumin-Bound Paclitaxel
• Other Study ID Numbers: QL1604-302

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No