A Study of LP002 for the Treatment of Patients With Malignant Digestive System Neoplasms

NCT04755543 | Unknown Phase 1

• 1 other identifier: LP002-I-02
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 6

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.

Conditions

Digestive System Neoplasms

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  up to approximately 24 months

Secondary Outcomes (14)

• Objective Response Rate (ORR) for Arm I-A, I-B, I-C, I-E

  up to approximately 24 months

• Disease Control Rate (DCR) for Arm I-A, I-B, I-C, I-E

  up to approximately 24 months

• Duration of Response (DOR) for Arm I-A, I-B, I-C, I-E

  up to approximately 24 months

• Progression-Free Survival (PFS) for Arm I-A, I-B, I-C, I-E

  up to approximately 24 months

• Overall survival (OS) for Arm I-A, I-B, I-C, I-D, I-E

  up to approximately 24 months

Study Arms (5)

I-A

EXPERIMENTAL

LP002 dose escalation (3+3 design): 6-12 patients with 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 will receive LP002 600mg or 900 mg by intravenous (IV) infusion on Day 1, every 2 weeks (Q2W), for up to 2 year.

Drug: LP002

I-B

EXPERIMENTAL

If the safety profile in Arm A is acceptable, 9-12 patients with 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 will receive LP002 600mg or 900 mg IV on Day 1, Q2W, for up to 2 year.

Drug: LP002

I-C

EXPERIMENTAL

If the safety profile in Arm A is acceptable, 15-20 patients with metastatic gastric carcinoma who are PD-L1 positive and systemic treatment-naive will receive LP002 900 mg IV on Day 1, Q2W, and Cisplatin 50mg/m2 IV on Day 1, Q2W, and Fluorouracil 2000 mg/m2 IV continuous infusion over 48 hours from Day 1, Q2W,for up to 2 year.

Drug: LP002; Drug: Cisplatin; Drug: Fluorouracil

I-D

EXPERIMENTAL

Perioperative treatment: If the safety profile in Arm A is acceptable, 15-20 patients with gastric or gastroesophageal junction carcinoma of cT2-4a, any N, M0 who are PD-L1 positive and systemic treatment-naive will receive LP002 900 mg IV on Day 1, Q2W, and Cisplatin 50mg/m2 IV on Day 1, Q2W, and Fluorouracil 2000 mg/m2 IV continuous infusion over 48 hours from Day 1, Q2W, for 3 cycles, 4-6 weeks before operation of the tumor and receive additional 6 cycles of the same therapy 4 weeks after the operation.

Drug: LP002; Drug: Cisplatin; Drug: Fluorouracil

I-E

EXPERIMENTAL

Dose escalation (3+3 design) of OH2 (an oncolytic virus) + LP002 900mg：If the safety profile in Arm A is acceptable, 15-30 patients with 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 will receive LP002 900mg IV on Day 1, Q2W, and OH2 10\^6 or 10\^7 or 10\^8 CCID50/mL by intra-tumoral injection, Q2W, for up to 2 year.

Drug: LP002; Biological: OH2 oncolytic virus

Interventions

LP002 DRUG

600mg or 900 mg by intravenous (IV) infusion on Day 1, every 2 weeks (Q2W).

I-A; I-B; I-C; I-D; I-E

Cisplatin DRUG

50mg/m2 IV on Day 1, Q2W

I-C; I-D

Fluorouracil DRUG

2000 mg/m2 IV continuous infusion over 48 hours from Day 1, Q2W

I-C; I-D

OH2 oncolytic virus BIOLOGICAL

106 or 107 or 108 CCID50/mL by intra-tumoral injection, Q2W

I-E

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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;
• Renal function: Serum creatinine (Scr) ≤1.5×ULN;
• 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;

You may not qualify if:

• 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:
• Nasal spray, inhalation or other local glucocorticoids.
• 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.

Sponsors & Collaborators

• Taizhou HoudeAoke Biomedical Co., Ltd.: lead

Study Sites (6)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

RECRUITING

Henan Cancer Hospital & Insititute

Zhengzhou, Henan, 450008, China

RECRUITING

Hubei Cancer Hospital & Insititute

Wuhan, Hubei, 430070, China

RECRUITING

Liaoning Cancer Hospital & Insititute

Shenyang, Liaoning, 110042, China

RECRUITING

The First Affiliated Hospital. Zhejiang University School Of Medicine

Hangzhou, Zhejiang, 310003, China

RECRUITING

The First Affiliated Hospital. Zhejiang University School Of Medicine

Hangzhou, Zhejiang, 310003, China

RECRUITING

MeSH Terms

Conditions

Digestive System Neoplasms

Interventions

Cisplatin; Fluorouracil

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Jing Huang, MD

CONTACT

010-87788113; huangjing@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2021
• First Posted: February 16, 2021
• Study Start: June 17, 2019
• Primary Completion: June 30, 2021
• Study Completion: June 30, 2022
• Last Updated: February 16, 2021

Record last verified: 2021-02

Locations

CN (6)