Study of SYSA1801 in the Treatment of Claudin( CLDN) 18.2 Positive Advanced Malignant Solid Tumor

NCT05009966 | Unknown Phase 1 FDA Drug

• 1 other identifier: SYSA1801-CSP-001
• Study Type: interventional
• Target: 272
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, dose escalation, dose expansion and extension cohort phase 1 study to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of SYSA1801

Conditions

Advanced Solid Tumor; Gastric Cancer (GC); Gastroesophageal Junction (GEJ) Cancer; Pancreatic Cancer

Outcome Measures

Primary Outcomes (3)

• Dose-Limiting Toxicity (DLT)

  DLT was defined as ≥grade 3 adverse events (per protocal and NCI CTCAE 5.0)related to the study drug that occurred in the first administration cycle (21 days) of SYSA1801

  Up to 21 days after the first dose of SYSA1801

• Recommended Phase 2 Dose (RP2D)

  RP2D may be selected based on the Maximum tolerated dose(MTD), pharmacokinetic and antitumor activity data

  Up to 24 months(end of treatment)

• Incidence, severity, and outcome of adverse events (AEs) and serious adverse events (SAEs)

  The adverse events occurring or worsening on or after the first dose of the study drug will be recorded

  Up to 30 days after the last dose of SYSA1801

Secondary Outcomes (7)

• Peak Plasma Concentration (Cmax)

  Predose and multiple timepoints up to 21 days after every dose (stage I)

• Time to maximum concentration(Tmax)

  Predose and multiple timepoints up to 21 days after every dose (stage I)

• Area under the plasma concentration versus time curve (AUC)

  Predose and multiple timepoints up to 21 days after every dose (stage I)

• Immunogenicity: anti-drug antibody(ADA)

  Predose and multiple timepoints up to 21 days after every dose (stage I)

• Objective Response Rate (ORR)

  Up to 24 months(end of treatment)

Study Arms (1)

SYSA1801 for injection

EXPERIMENTAL

Stage I: Dose Escalation and dose expansion： Dose Escalation：SYSA1801 will be administered intravenously (IV) at different dose levels, including 0.5, 1, 2, 3, 4.5 and 6 mg/kg according to a modified 3+3 dose-escalation design. Accelerated dose titration design will be used for the first 2 dose levels (0.5 and 1 mg/kg), and then traditional 3+3 dose escalation design will be used for the following levels (2, 3, 4.5 and 6 mg/kg). Dose expansion: SYSA 1801 will be administered at up to dose levels which is equal or lower than MTD IV infusion. Each dose level contains no more than 12 subjects (including subjects in dose escalation) Stage II: Extension cohort This cohort will comprise subjects with Claudin 18.2 positive GC or GEJ adenocarcinoma, pancreatic cancer or other solid cancer with prior failure of, progression on, or intolerance to, standard therapy. The starting dose of SYSA1801 for expansion will be derived from the RP2D determined during Stage I

Drug: SYSA1801 for injection

Interventions

SYSA1801 for injection DRUG

SYSA1801 will be administered intravenously (IV) on Day 1 of every 21-day cycle. Individual subjects may continue study treatment until there is evidence of disease progression (clinical or radiologic) judged by Investigators, unacceptable toxicity or other reasons for treatment discontinuation.

SYSA1801 for injection

Eligibility Criteria

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

You may qualify if:

• Subjects provide documented informed consent voluntarily;
• Male or female subjects ≥ 18 years and ≤ 75 years;
• Subjects with locally advanced unresectable or metastatic malignant solid tumors confirmed by histology and/or cytology and CLDN 18.2 positive expression in the tumor tissue confirmed by the central laboratory: dose-escalation phase defined as IHC ≥ 1+ by central laboratory IHC assay; dose-expansion phase and extension cohort studies defined as CLDN18.2 expression in ≥ 40% of tumor cells, the IHC ≥ 2+);
• Subjects met following requirements according to the different stages: Stage I: subjects have no standard treatment, or the standard treatment failed or was intolerant, or have no condition to receive standard treatment; Stage II: Subjects had received at least one prior line of systemic chemotherapy with clear disease progression confirmed by investigator or documented by medical records, in the following phase II cohorts:
• Cohort A: Gastric cancer/adenocarcinoma of gastroesophageal junction Cohort B: Pancreatic cancer Cohort C: Non-small cell lung cancer Cohort D: Other solid tumors expressing CLDN 18.2;
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0 or 1, and life expectancy ≥ 3 months;
• At least one measurable lesion according to RECIST1.1;
• The main organ function met the following criteria within 7 days before enrollment (no blood transfusion, EPO, G-CSF or other medical support treatment within 14 days before administration of study drug): neutrophil ≥ 1.5 × 10\^9 /L, platelet ≥ 100 × 109/L, hemoglobin ≥ 90 g/L or ≥ 5.6 mmol/L; International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × Upper limit of normal range (ULN), activated partial thrombin time (APTT) ≤ 1.5 × ULN, serum creatinine ≤ 1.5 × ULN, total bilirubin (TBIL) ≤ 1.5 × ULN (≤ 3 × ULN for subjects with Gilbert's syndrome or liver metastasis), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN for subjects with liver metastasis);
• Fertile women must have negative pregnancy tests before study entry;
• Men and fertile women must agree to take effective contraceptive measures from signing informed consent to 6 months after the last administration;
• Understand the trial requirements, and willing to follow the trial and follow-up procedures.

You may not qualify if:

• Pregnant or lactating women;
• Subjects who have not recovered from the adverse reactions caused by previous anti-tumor treatment (refer to NCI CTCAE 5.0, ≤ grade 1 or at baseline), except for the toxicity of alopecia, pigmentation and other conditions have no safety risk according to investigators' opinion;
• Antitumor therapy such as chemotherapy, radiotherapy, biotherapy, targeted therapy, immunotherapy and other anti-tumor treatment within 4 weeks before administration of the study drug, and the following items: Nitrosourea (such as carmustine, lomustine, etc.) or mitomycin C were within 6 weeks before administration of the study drug; Oral fluorouracil and small molecule targeted drugs within 5 half-lives before administration of the study drug; Endocrine therapy or traditional Chinese medicines with anti-tumor indications within 2 weeks before administration of the study drug; Palliative radiotherapy for bone metastasis or local radiotherapy for pain relief within 2 weeks before administration of the study drug; Drugs for bone metastasis related events (such as zoledronic acid, etc.) did not affect the enrollment;
• Subjects who have undergone major surgery (excluding needle biopsy) within 4 weeks before administration of the study drug, or who are expected to undergo major surgery during the study period, or who have severe unhealed wounds, trauma, ulcers, etc;
• Subjects with previous intolerance to CLDN 18.2 monoclonal antibody or known components of SYSA1801, or severe allergic reactions;
• Subjects with symptoms of brain or pia mater metastasis; Subjects with central nervous system (CNS) metastases in the following conditions can be considered: subjects with brain metastases without treatment and without symptoms, or with imaging evidence of progression free status lasting for at least 4 weeks after treatment, and without hormone or antiepileptic treatment for at least 4 weeks;
• Subjects with body cavity effusion (pleural effusion, ascites, pericardial effusion, etc.) that need local treatment or repeated drainage, and which are poorly controlled by the investigators' judgment;
• Concurrent other malignant tumors (except history of the following tumors that occurred and were cured 5 years ago: non-melanoma, skin cancer, carcinoma in situ or non-invasive tumor);
• Active colitis, including infectious colitis, radiation colitis and ischemic colitis, within 4 weeks before administration of the study drug;
• Pyloric obstruction or persistent recurrent vomiting (defined as vomiting ≥ 3 times in 24 hours);
• Peripheral neuropathy ≥ grade 2 (refer to NCI CTCAE 5.0);
• Subjects with active hepatitis B or C (HBsAg positive and/or HBcAb positive with HBV DNA titer more than 1000 copies/mL or 200 IU/mL; HCV Ab positive with HCV RNA titer higher than the upper limit of normal value);
• HIV positive or syphilis infection requiring systematic treatment;
• Subjects who have received systemic immunosuppressive therapy, including glucocorticoids, within 2 weeks before administration of the study drug; Subjects allowed to use physiological replacement dose of hydrocortisone or similar drugs;
• Subjects with active autoimmune diseases requiring systemic immunosuppressive therapy in the past 2 years;

Sponsors & Collaborators

• CSPC ZhongQi Pharmaceutical Technology Co., Ltd.: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms; Neoplasms; Pancreatic Neoplasms

Interventions

Injections

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Shen Lin, Ph.D

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shen Lin, Ph.D

CONTACT

861088196561; doctorshenlin@sina.cn

Gong Jifang, Ph.D

CONTACT

861088196561; goodjf@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2021
• First Posted: August 18, 2021
• Study Start: September 16, 2021
• Primary Completion: December 1, 2023
• Study Completion: June 1, 2024
• Last Updated: October 25, 2021

Record last verified: 2021-08

Locations

CN (1)