Clinical trial NCT04755543: A Study of LP002 for the Treatment of Patients With Malignant Digestive System Neoplasms
Official title: A Phase I Study of Safety and Pharmacokinetics of LP002 (a Humanized Monoclonal Antibody Targeting PD-L1) in Patients With Malignant Digestive System Neoplasms
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Digestive System Neoplasms
Lead sponsor: Taizhou HoudeAoke Biomedical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-02-16
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: LP002 is a humanized monoclonal antibody targeting programmed death ligand-1 (PD-L1), which prevents PD-L1 from binding to PD-1 and B7.1 receptors on T cell surface, restores T cell activity, thus enhancing immune response and has potential to treat various types of tumors. In this study, the safety, pharmacokinetics and preliminary efficacy of LP002 for the treatment of malignant digestive system neoplasms will be evaluated.


Eligibility criteria: Inclusion Criteria:

* Understood and signed an informed consent form.
* Age ≥ 18 and ≤ 75 years old, male or female.
* Has histologically confirmed diagnosis of:

Malignant digestive system neoplasms (mainly include gastric/ gastroesophageal junction/ esophageal carcinoma) failed (experienced progressed disease or unable to tolerate) at least one line of previously standard treatment for Arm I-A.

Malignant gastric/ gastroesophageal junction carcinoma who are PD-L1 positive and failed (experienced progressed disease or unable to tolerate) at least two lines of previously standard treatments for Arm I-B.

Metastatic gastric carcinoma who are PD-L1 positive and systemic treatment-naive for Arm I-C.

Gastric or gastroesophageal junction carcinoma of cT2-4a, any N, M0 who are PD-L1 positive and systemic treatment-naive for Arm I-D.

Advanced solid tumors (mainly include digestive system neoplasms) who failed (experienced progressed disease or unable to tolerate) at least one line of previously standard treatment or lack of standard treatments and has suitable lesions for intratumoral injection for Arm I-E.

* Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Score.
* Life expectancy ≥ 3 months.
* Has at least one measurable extracranial lesion according to RECIST1.1 (except Arm-D).
* Has sufficient organ and bone marrow function to meet the following laboratory examination standards:

  1. Blood routine: absolute neutrophil count (ANC)≥1.5×10\^9/L; while blood cell count (WBC)≥3×10\^9/L; platelet count (PLT)≥100×10\^9/L;hemoglobin (HGB)≥90 g/L;
  2. Renal function: Serum creatinine (Scr) ≤1.5×ULN;
  3. Liver function: TBIL≤1.5×ULN; Patients without liver metastases require alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5× ULN. Patients with liver metastases require: ALT and AST≤5×ULN;
  4. The coagulation function is adequate, which is defined as the international normalized ratio (INR) ≤ 2×ULN; or activated partial thromboplastin time (APTT)≤ 1.5×ULN;
* Reproductive men and women of childbearing age are willing to take effective contraceptive measures from signing the informed consent form to 3 months after the last administration of the trial drug.
* Willing to provide tissue samples for PD-L1 biomarker analysis.

Exclusion Criteria:

* Suffered from other malignant tumors in the past 5 years，except those with low risk of metastasis and death (5-year survival rate \>90%), for instance, skin basal cell carcinoma, squamous cell carcinoma, and carcinoma in situ from cervix or other regions that have been adequately treated);
* Had prior treatment with any anti-programmed cell death-1 (PD-1), or PD-ligand 1 (PD-L1) or CTLA-4 agent or other immune checkpoint inhibition therapies.
* has active or a history (with high chance of recurrence) of autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, vasculitis, nephritis, except: Type I Diabetes being treated with fixed dose of insulin, hypothyroidism or Hashimoto's thyroiditis that can be controlled only by hormone replacement therapy, skin diseases that do not require systemic treatment (such as eczema, rash covering \<10% body surface area, psoriasis without ocular symptoms).
* Expected to undergo major surgery during the study treatment or within 28 days before the first administration of the study drug.
* Has received systemic corticosteroids or other immunosuppressive drugs within 2 weeks before the first administration of the study drug, excluding:

  1. Nasal spray, inhalation or other local glucocorticoids.
  2. Short-term (≤ 7 days) use of glucocorticoids as a preventive medication for allergic reactions or as a therapeutic medication for non-autoimmune diseases.
* Has active digestive ulcer, incomplete intestinal obstruction, active gastrointestinal hemorrhage or perforation.
* Has active interstitial pneumonia, pulmonary fibrosis, acute pulmonary disorders, acute radiation pneumonitis，et al.
* Has uncontrolled systemic diseases, for instance, cardiovascular and cerebrovascular disease, diabetes, tuberculosis.
* Has a history of HIV infection, or other acquired or innate immune deficiency disorders, or a history of organ or stem-cell transplantation.
* Has active chronic HBV or HCV infection, except those with HBV DNA viral load ≤500 IU/mL or \<10\^3 copies/mL, or HCV RNA negative after adequate treatment.
* Has severe infection within 4 weeks or active infection requiring IV infusion of antibiotics within 2 weeks prior to the first administration of the study drug.
* Known to be allergic to macromolecular protein agents or monoclonal antibody; Known to has a history of severe allergies to any of the components in the study drug;
* Has participated in other clinical trial within 4 weeks before the first administration of the study drug.
* Alcohol dependence or drug abuse within recent one year.
* Has a history of confirmed neurological or mental disorders, such as epilepsy, dementia; or with poor compliance; or the presence of peripheral neurological disorders.
* Has brain metastasis with symptoms.
* Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial.
* Has received a live vaccine within 30 days prior to the first dose of trial treatment.
* Other reasons disqualifying the entering of this study based on the evaluation of the investigators.

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: up to approximately 24 months
Secondary outcomes:
measure: Objective Response Rate (ORR) for Arm I-A, I-B, I-C, I-E
timeFrame: up to approximately 24 months
measure: Disease Control Rate (DCR) for Arm I-A, I-B, I-C, I-E
timeFrame: up to approximately 24 months
measure: Duration of Response (DOR) for Arm I-A, I-B, I-C, I-E
timeFrame: up to approximately 24 months
measure: Progression-Free Survival (PFS) for Arm I-A, I-B, I-C, I-E
timeFrame: up to approximately 24 months
measure: Overall survival (OS) for Arm I-A, I-B, I-C, I-D, I-E
timeFrame: up to approximately 24 months
measure: R0 resection rate for Arm I-D
timeFrame: up to approximately 12 months
measure: pathological complete response rate (pCR rate)
timeFrame: up to approximately 12 months
measure: Terminal half life of LP002
timeFrame: up to approximately 12 months
measure: Area under curve of LP002
timeFrame: up to approximately 12 months
measure: Apparent volume of distribution of LP002
timeFrame: up to approximately 12 months
measure: Systemic clearance of LP002
timeFrame: up to approximately 12 months
measure: Cmax of LP002
timeFrame: up to approximately 12 months
measure: Tmax of LP002
timeFrame: up to approximately 12 months
measure: Serum concentration of the antibody against LP002 within 1 hour prior to each administration
timeFrame: up to approximately 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Zhengzhou
country: China
facility: Henan Cancer Hospital & Insititute
state: Henan
city: Wuhan
country: China
facility: Hubei Cancer Hospital & Insititute
state: Hubei
city: Shenyang
country: China
facility: Liaoning Cancer Hospital & Insititute
state: Liaoning
city: Hangzhou
country: China
facility: The First Affiliated Hospital. Zhejiang University School Of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: The First Affiliated Hospital. Zhejiang University School Of Medicine
state: Zhejiang
Study officials:
References: