Clinical trial NCT04322006: A Phase I/II Study of TJ004309 for Advanced Solid Tumor
Official title: A Phase I/II Study of Evaluating the Safety, Tolerance, Pharmacokinetics, Pharmacodynamics and Curative Effect of Dose Escalation and Extension for Single Drug TJ004309 and Toripalimab Combine Treatment for Advanced Solid Tumor
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Lead sponsor: TJ Biopharma Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-03-26
Enrollment: 376
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 study is a phase I/II study of single drug TJ004309 and Toripalimab combine treatment for Advanced solid tumor. This study include two stages. First stage is dose escalation and second stage is dose extension. The purpose of part A is to confirm the MTD or MED and the clinical dose. The purpose of part B is to observe the safety, effectiveness, Pharmacokinetics, pharmacodynamics and biomarker properties for effective subjects.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
* In the dose-escalation phase, subjects with advanced solid tumors that are histologically or cytologically confirmed to be unresectable or have metastasized, subjects with standard treatment failure or intolerance (disease progression, or inability to tolerate chemotherapy, targeted therapy, etc.), or subjects without effective treatment.
* Synchronous dose expansion (will base on dose-escalation phase)
* At least one measurable disease by modified RECIST 1.1 for immune based therapeutics V1.1
* Expected survival ≥ 3 months
* Adequate organ function as defined by the following criteria:

  * Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 times upper limit of normal (ULN)
  * Total serum bilirubin ≤ 1.5 times the ULN
  * Absolute neutrophil count (ANC) ≥ 1.5 ×109/ L
  * Platelets ≥ 100×109/ L without transfusion support within 28 days prior to study treatment
  * Hemoglobin ≥ 9.0 g/dL without transfusion support within 14 days prior to study treatment
  * Serum creatinine ≤ 1.5 times the ULN or Creatinine clearance \> 30 mL/min by Cockcroft-Gault formula
  * International normalized ratio (INR) in normal range
* Serum pregnancy test must be negative for childbearing female prior to study treatment
* The man have reproductive ability or childbearing female (refers to men and women not on birth control operation, and the menopause women), must use the highly effective contraceptive methods (such as oral contraceptives, intrauterine contraceptive device, abstemious sexual desire or barrier contraceptive method combined with spermicide) during the study, and sustain contraception 6 months after the last dose
* Willingness and ability to consent for self to participate in study and comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Exclusion Criteria:

* Pregnancy or breastfeeding
* Prior T-cell therapy
* Receipt of systemic anticancer therapy or ≥ 5 times the elimination half-life of the drug has elapsed within 2 weeks prior to study treatment (Note: whichever is shorter shall prevail.)
* Exist ≥ 2 kinds of primary tumor, expect cured preinvasive carcinoma and basaloma. (patients are not excluded if ≥ 5 years treatment with other tumor prior to study treatment.)
* Autoimmune disease requiring treatment within the past twelve months only requiring related treatment replacement
* Condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications more than 7 days within 14 days prior to study treatment (Note: inhaled and topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.)
* Current treatment on another therapeutic clinical trial within 14 days prior to study treatment
* Major surgical procedure or significant traumatic injury within 4 weeks prior to study treatment and no date of surgery (if applicable) or anticipated need for a major surgical procedure planned during study treatment
* Chest radiotherapy ≤ 4 weeks, wide field radiotherapy ≤ 4 weeks (defined as \> 50% of volume of pelvic bones or equivalent) or palliative radiotherapy ≤ 2 weeks prior to study treatment
* Brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease, unless the lesion(s) have been radiated or resected, are considered fully treated and inactive, are asymptomatic, and no steroids have been administered for central nervous system disease over the 2 weeks prior to study treatment
* Known active viral or nonviral hepatitis or cirrhosis, except patients with Hepatitis C infection and undetectable virus following treatment are eligible.
* Known human immunodeficiency virus (HIV) positive
* Ascites or pericardial effusion that can not be control
* History of or active interstitial lung disease
* Hypertension is not well controlled by medication. Hypertension defined as blood pressure (BP) systolic \> 150 or diastolic \> 90 mm Hg (Note: Initiation or adjustment of antihypertensive medication prior to study entry is allowed provided that the average of the three most recent BP readings prior to study enrollment is ≤150/90 mm Hg.)
* Cardiovascular diseases with clinical significance, include phase II-III cardiac insufficiency defined by New York Heart Association, myocardial infarction (MI) within 3 months prior to study treatment, symptomatic congestive heart failure, cerebral infarction within 3 months prior to study treatment, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG) within 6 months prior to study treatment
* Deep-venous thrombosis within 6 months prior to study treatment (except treated without warfarin 2 weeks prior to study treatment)
* Thrombolytic use (except to maintain IV catheters) within 10 days prior study treatment
* Any active infection requiring systemic treatment
* Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for this study

Primary outcomes:
measure: Dose Limiting Toxicities(DLT)
timeFrame: 28days after first dose for QW, 21days after first dose for Q3W
measure: MTD
timeFrame: 2 years
measure: MED
timeFrame: 2 years
measure: Recommend dose of TJ004309
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Cancer Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Chongqing
country: China
facility: Army Medical Center of PLA
state: Chongqing
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
state: Chongqing
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial Hospital of Chinese Medicine
state: Guangdong
city: Shantou
country: China
facility: Cancer Hospital affiliated to Shantou University Medical College
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Haerbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Yangzhou
country: China
facility: Northern Jiangsu People's Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: The First Bethune Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: Liaoning Cancer Hospital and Institute
state: Liaoning
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi 'an Jiaotong University
state: Shaanxi
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Chengdu
country: China
facility: Sichuan Cancer Hospital
state: Sichuan
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hanzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References: