A Study of MSB0254 Injection in Advanced Solid Tumors

NCT04381325 | Terminated Phase 1

• 1 other identifier: MSB0254-CSP-001
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

This study was an open, multi-dose dose escalation phase I clinical study to evaluate the safety, tolerability and PK characteristics of MSB0254 in patients with locally advanced or metastatic solid tumors, and to preliminarily measure its anti-tumor efficacy.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of MSB0254

  Measured by number adverse events that are related to treatment

  Up to 90 days following the last dose

• Maximum tolerated dose(MTD) or recommended phase2 dose（RP2D）

  Measured by number of subjects experiencing DLT in each escalation cohort

  Up to 90 days following the last dose

Secondary Outcomes (8)

• Area under the plasma concentration versus time curve (AUC) for MSB0254

  Up to 30 days following the last dose

• Peak Plasma concentration (Cmax)for MSB0254

  Up to 30 days following the last dose

• Time to the Maximum Observed Plasma Concentration (Tmax)

  Up to 30 days following the last dose

• Terminal elimination half-life (t1/2)

  Up to 30 days following the last dose

• The immunogenicity of MSB0254 injection

  Up to 30 days following the last dose

Study Arms (1)

MSB0254 Injection

EXPERIMENTAL

This experiment will start from 4mg/kg with a dose increase of 3+3, and is planned to be carried out in 5 dose groups, namely 4mg/kg, 8mg/kg (100% increase), 12mg/kg (50% increase), 16mg/kg (33% increase) and 20mg/kg (25% increase).MSB0254 injection was administered intravenously on day 1 and day 15 every 28 days.To collect pharmacokinetic blood samples after repeated administration, MSB0254 injection was not administered on day 1 of the third cycle (C3D1).The observation period of DLT was 28 days after the first administration. An intravenous infusion with concentration 20 mg/kg every 3 weeks (Q3W).

Drug: MSB0254 Injection

Interventions

MSB0254 Injection DRUG

An intravenous infusion with concentration from 4 mg/kg to 16 mg/kg every 2 weeks (Q2W). An intravenous infusion with concentration 20 mg/kg every 3 weeks (Q3W).

MSB0254 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:

• Voluntary informed consent, knowledge of the study and willingness to follow and has ability to complete all trial procedures
• There is a histologically or cytologically confirmed, locally advanced or metastatic tumor by standard treatment failure or lack of standard treatment or inability to tolerate standard treatment;
• For patients enrolled in the extended period:
• Group 1: vascular rich tumors, including but not limited to neuroendocrine tumors, thymic squamous cell carcinoma and soft tissue Sarcoma, the specific categories are as follows. If it is necessary to enroll other types of tumor subjects, it is necessary to cooperate with the sponsor The responsible person shall discuss and confirm.
• Neuroendocrine tumor (net): low and medium grade (G1 or G2) confirmed by histopathology: low grade Other (G1) was defined as mitotic image number \< 2 / 10, high power field of view \[HPF\] and / or Ki-67 differentiation Index \< 3%; The intermediate level (G2) is defined as the number of mitotic images 2-20 / 10 high-power field of vision\[HPF\] and / or Ki-67 differentiation index 3-20%. If the mitotic image and Ki of the same tumor tissue-67 indicators correspond to different levels and follow higher levels;
• Thymic squamous cell carcinoma (TSCC): thymic squamous cell carcinoma confirmed by histology or cytology;
• Soft tissue sarcoma (STS): soft tissue sarcoma confirmed by histology or cytology;
• Group 2: hepatocellular carcinoma (HCC): hepatocellular carcinoma confirmed histologically or cytologically. Barcelona Clinic Liver cancer stage B and C (BCLC B and C)
• The eastern United States cooperative tumor group (ECOG) score was 0 or 1
• Expect to survive at least 3 months
• Must have at least one assessable lesion as defined in RECIST v1.1;
• Suitable organs and hematopoietic function should be available. Laboratory tests during screening should meet the appropriate criteria:
• Male and female subjects of childbearing age will agree to use effective, investigator-approved contraceptive methods from the date of the informed consent until 3 months after the last administration
• Previous treatment of subjects enrolled in the extended study:
• Net: Net subjects with disease progression after at least 2-wire system antitumor drug treatment regimen: connected Systematic treatment for unresectable net, followed by recurrence / progression, or intolerance, or Unwilling to receive treatment. Frontline treatment may include somatostatin analogues, interferon, PRRT (peptide) Receptor radionuclide therapy), mTOR inhibitor or chemotherapy (unlimited chemotherapy drugs and times, Chemotherapy is regarded as a drug treatment regimen), anti angiogenesis drugs (including anti VEGF-A monoclonal antibody) Or VEGFR tyrosine kinase inhibitor);

You may not qualify if:

• Had suffered from malignant tumors other than the primary tumor at the time of enrollment within 5 years before screening (except: after Fully treated cervical carcinoma in situ, local squamous cell carcinoma of the skin, basal cell carcinoma, localized cancer Adenocarcinoma, ductal carcinoma in situ or stage I uterine cancer);
• High grade (G3) neuroendocrine carcinoma, adenoid carcinoma, islet cell carcinoma, goblet cell carcinoid, large Cellular neuroendocrine carcinoma and small cell carcinoma;
• Functional net and need to be accompanied by the use of long-acting somatostatin analogues to control symptoms, such as insulinoma Gastrinoma, glucagon tumor, somatostatin tumor, adrenocorticotropic hormone tumor, vascular activity Intestinal peptidoma with carcinoid syndrome, zoai syndrome or disease-specific active symptoms-
• Patients with symptoms of brain or pia meningeal metastases.
• The lung metastasis of the tumor has a cavity, or the investigator judges that there is bleeding tendency or bleeding risk;
• patients requiring local treatment or repeated drainage, the investigator identified poorly controlled effusion of the body cavity (pleural fluid, ascites, pericardial effusion, etc.)
• The adverse reactions of previous treatment did not recover to CTCAEv5.0 score ≤1 (excluding hair loss and anemia);
• Had received any previous systemic therapy targeting VEGF or VEGFR2 signaling pathway;
• Drugs or chemotherapy or radiotherapy received in other clinical trials within 4 weeks prior to enrollment (mitomycin C and nitrosorea should be administered at least 6 weeks before the last dose)
• Patients who had major surgery within 4 weeks prior to screening (excluding needle biopsy) and who were expected to have major surgery during the study period (including the 28-day screening period) or had severe unhealed wounds, ulcers, or trauma
• Left ventricular ejection fraction ≤50%;
• Heart failure patients with greater than or equal to Ⅱ level（NYHA）;
• Clinically significant arrhythmias (including frequent ventricular premature beats, symptomatic or treatable ventricular tachycardia, and asymptomatic persistent ventricular tachycardia);
• After regular antihypertensive treatment for 4 weeks, the blood pressure did not reach systolic blood pressure \< 150mmhg and / or diastolic blood pressure \< 150mmhg 90mmHg, or after regular antihypertensive treatment, the blood pressure reaches systolic blood pressure \< 150mmhg and / or diastolic blood pressure The duration of pressure \< 90mmHg is less than 4 weeks
• There are currently venous thromboemboli that require treatment;

Sponsors & Collaborators

• Suzhou Transcenta Therapeutics Co., Ltd.: lead

Study Sites (2)

The First Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, 310003, China

Location

FuDan University ZhongShan Hospital

Shanghai, China

Location

Study Officials

• Mengde Wang

  Suzhou Transcenta Therapeutics Co., Ltd.

  STUDY DIRECTOR

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: May 7, 2020
• First Posted: May 8, 2020
• Study Start: April 1, 2020
• Primary Completion: June 8, 2022
• Study Completion: June 8, 2022
• Last Updated: April 5, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)