Clinical trial NCT04326829: QL1604 Monotherapy for dMMR or MSI-H Advanced Solid Tumors
Official title: A Single-arm, Multi-center, Phase Ⅱ Clinical Study to Evaluate Efficacy and Safety of QL1604 Monotherapy for the Treatment of Unresectable or Metastatic Mismatch Repair Deficient (dMMR) or Microsatellite Instability-high (MSI-H) Solid Tumors That Failed to Respond to Standard Therapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Advanced Malignant Tumor
Lead sponsor: Qilu Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-03-30
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this study, patients with previously-treated locally-advanced or metastatic mismatched repair deficient (dMMR) or microsatellite instability-high (MSI-H) colorectal carcinoma (CRC) and other solid tumors will be treated with QL1604 monotherapy.


Eligibility criteria: 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. Histologically confirmed locally advanced or metastatic dMMR or MSI-H status colorectal carcinoma or other malignant solid tumors;
4. At least one measureable lesion as defined per RECIST Version (v) 1.1 ;
5. Subjects who have disease progression or intolerable reactions after the currently available standard anti-cancer treatment previously received or refused prior cancer therapy regimen(s) ;
6. Subjects must provide tumor tissues and blood samples for the determination of MSI, tumor mutational burden (TMB), PD-L1 expression level;
7. Eastern Cooperative Oncology Group performance status of 0 or 1;
8. Life expectancy of greater than 12 weeks;
9. Adequate hematologic and organ function;
10. Female subjects who are not pregnant or breastfeeding
11. Male and female subjects able to have children must agree to use highly effective method of contraception throughout the study and for at least 120 days after last dose.

Exclusion Criteria:

1. Known hypersensitivity to any monoclonal antibody, QL1604 and/or any of its excipients;
2. Subjects with known central nervous system (CNS) metastasis;
3. Active autoimmune disease that has required systemic treatment in past 2 years, replacement therapy is acceptable;
4. Subjects with major cardiovascular and cerebrovascular diseases;
5. Subjects with uncontrollable pleural effusion, pericardial effusion or ascites;
6. Any condition that required systemic treatment with either corticosteroids (\> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before the first dose of study drug;
7. Subjects who have received surgery, radiotherapy, chemotherapy, targeted therapy, other anti-tumor treatments, or participating in other clinical studies is less than 4 weeks before the first administration of investigational product;
8. Subjects who have not recovered to CTC AE Grade 1 or better from related side effects of any prior antineoplastic therapy;
9. Received a live vaccine within 30 days of planned start of study medication;
10. Infection with human immunodeficiency virus (HIV), HAV, HBV and HCV;
11. Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand 1 (anti-PD-L1), anti-PD-L2 agent, cytotoxic lymphocyte associated protein-4 (CTLA-4), OX-40, CD137;
12. Known psychiatric or substance abuse disorders that would interfere with the requirements of the study;
13. History or current evidence of any condition, therapy, or laboratory abnormality, that might confound the results of the trial, or interfere with the participant's participation for the full duration of the study, or investigators/sponsor consider the subjects are not suitable for this trial.

Primary outcomes:
measure: ORR
timeFrame: up to 2 years
Secondary outcomes:
measure: ORR
timeFrame: up to 2 years
measure: 6-month PFS rate
timeFrame: the proportion of subjects who have time interval over 6 months between the first dose and disease progression or death
measure: 6-month OS rate
timeFrame: from the date of first dose until the date of 6-month
measure: PFS
timeFrame: from the first dose until firstly confirmed and recorded disease progression or death (whichever occurs earlier), assessed up to 2 years
measure: PFS
timeFrame: from the first dose until firstly confirmed and recorded disease progression or death (whichever occurs earlier), assessed up to 2 years
measure: OS
timeFrame: from the date of first dose until the date of death from any cause， assessed up to 2 years
measure: DOR
timeFrame: from the date when CR or PR (whichever recorded earlier) is firstly achieved until the date when disease progression or death is firstly recorded (whichever occurs earlier), assessed up to 2 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Cancer Hospital
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
Study officials:
References: