Evaluation of the Safety and Efficacy of NBL-015 in Patients With Advanced Solid Tumors

NCT05153096 | Unknown Phase 1

• 1 other identifier: NBL-015-CSP-001
• Study Type: interventional
• Target: 410
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is an open-label, multicenter, dose-escalation and cohort-expansion Phase I clinical study in patients with advanced solid tumors. The aim of this study is to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of NBL-015 in patients with advanced solid tumors.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (10)

• Incidence of adverse events (AEs)

  Incidence of adverse events (AEs) of single and multiple dose (according to NCI CTCAE 5.0).An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

  Approximately 4 years

• Incidence of serious adverse events (SAEs)

  Incidence of serious adverse events (SAEs) of single and multiple dose (according to NCI CTCAE 5.0).

  Approximately 4 years

• Maximum tolerated dose (MTD) (if available)

  MTD is defined as the prior dose level below the dose level at which 2/6 subjects suffer dose limiting toxicities.

  Approximately 1 year

• Dose Limiting Toxicity (DLT )

  Dose-limiting toxicity in patients with advanced tumors treated by NBL-015.

  Up to 28 days after first injection

• Recommended Phase 2 dose (RP2D)

  RP2D will be determined using available safety and efficacy data.

  Approximately 2 years

• Objective response rate (ORR) (in stage Ⅱ)

  Percentage of participants with CR or PR.

  Approximately 2 years in stage Ⅱ

• Disease control rate (DCR) (in stage Ⅱ)

  Percentage of participants with CR or PR or SD.

  Approximately 2 years in stage Ⅱ

• Duration of response (DOR) (in stage Ⅱ)

  DOR is defined as the time from first objective response (CR or PR per RECIST v 1.1) to first occurrence of objective tumor progression (progressive disease per RECIST v 1.1) or death from any cause, whichever occurs first.

  Approximately 2 years in stage Ⅱ

• Progression-free survival (PFS) (in stage Ⅱ)

  PFS is defined as the time from first dose to the first observation of disease progression (based on central reading) or death from any cause (as assessed by the independent reviewer).

  Approximately 2 years in stage Ⅱ

• Overall survival (OS) (in stage Ⅱ)

  OS is defined as the time from first dose to death from any cause.

  Approximately 2 years in stage Ⅱ

Secondary Outcomes (17)

• Pharmacokinetic (PK)

  Up to 21 Days after the sixth injection in stage I, after the fifth injection in stage II.

• Pharmacokinetic (PK)

  Up to 21 Days after the sixth injection in stage I, after the fifth injection in stage II.

• Pharmacokinetic (PK)

  Up to 21 Days after the sixth injection in stage I, after the fifth injection in stage II.

• Pharmacokinetic (PK)

  Up to 21 Days after the sixth injection in stage I, after the fifth injection in stage II.

• Pharmacokinetic (PK)

  Up to 21 Days after the sixth injection in stage I, after the fifth injection in stage II.

Study Arms (1)

Experimental: solid tumors

EXPERIMENTAL

Dose-escalation stage: Patients will receive NBL-015 once every two or three weeks, starting at a dose of 1 mg/kg. Cohort-expansion stage: Patients will receive NBL-015 at selected dose as per the results of dose-escalation stage.

Drug: NBL-015

Interventions

NBL-015 DRUG

NBL-015 by intravenous infusion

Experimental: solid tumors

Eligibility Criteria

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

You may qualify if:

• Age ≥18, ≤75 years, (subject to the date of signing the informed consent) who voluntarily sign the informed consent.
• Positive expression of Claudin 18.2 which is defined as moderate to severe membrane staining (2+/3+) in ≥50% of tumor cells tested by central laboratory immunohistochemistry (IHC).
• Histologically or cytologically confirmed diagnosis of advanced or metastatic solid tumors.
• At least one measurable lesion as per RECIST version 1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
• Life expectancy ≥12 weeks.
• Adequate major organ function within 7 days prior to treatment.
• Serum pregnancy tests were negative in women of reproductive age (WOCBP) within 7 days prior to initial use of the investigational drug. Patients and their spouses must agree to take adequate contraceptive measures from the time of signing the informed consent until 6 months after the last dose. During this period, women are not breastfeeding and men avoid sperm donation.

You may not qualify if:

• A history of other malignancies within 3 years prior to first dose, except for locally curable cancers.
• Patients with central nervous system metastases.
• Gastrointestinal abnormalities include:
• A) Pyloric obstruction or persistent recurrent vomiting (defined as ≥3 times of vomiting in 24 hours); B) There is a high risk of gastrointestinal bleeding or that there are other gastrointestinal abnormalities affecting the drug toxicity assessment determined by the investigator.
• Patient with a history of serious cardiovascular disease.
• Patients with active hepatitis B or C, or active syphilis infection, or HIV positive.
• Patients who are known to have severe allergic reactions and/or contraindications to prescription ingredients of NPL-015 or monoclonal antibodies, or who are intolerant to combination drugs;
• Patients who underwent major surgery (excluding needle biopsy) within 4 weeks prior to initial use of the investigational drug, or who required elective surgery during the trial period, or who had severe unhealed wounds, traumatic ulcers, etc.
• Toxicity of previous antitumor therapy did not return to grade 1 or below (CTCAE V5.0), except for toxicity of alopecia and other toxicity that researchers judged to have no safety risk.
• Patients have previously been treated with a drug targeting Claudin18.2.
• The time interval between the last anti-tumor treatment and the first use of experimental drug should meet the following requirements:
• A) Received antitumor therapy such as chemotherapy, radiotherapy (except local radiation therapy for pain relief), targeted therapy, immunotherapy, and other investigational agents within 4 weeks prior to initial administration; B) Received oral fluorouracil, small-molecule targeted drugs and traditional Chinese medicine with anti-tumor indications within 2 weeks prior to initial administration.
• Receiving a corticosteroid (prednisone\>10 mg/ day or equivalent dose of the same kind of drug) or other immunosuppressant treatment, except for:
• A) Local, ocular, intraarticular, intranasal, and inhaled glucocorticoids; B) Short-term use of glucocorticoids for prophylactic treatment (e.g. to prevent contrast allergy).
• Live attenuated vaccine is received within 2 weeks prior to the first use of the investigational drug or is planned for the study period.

Sponsors & Collaborators

• NovaRock Biotherapeutics, Ltd: lead

Study Sites (1)

Zhongshan Hospital affiliated to Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

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: November 29, 2021
• First Posted: December 10, 2021
• Study Start: April 1, 2022
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: January 3, 2022

Record last verified: 2021-11

Locations

CN (1)