A Phase I/II Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of IBB0979 in Patients With Locally Advanced or Metastatic Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- IBB0979
- Conditions
- Advanced Malignant Tumors
- Sponsor
- SUNHO（China）BioPharmaceutical CO., Ltd.
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Frequency of adverse events (AEs) and SAEs (Phase Ⅰ)
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a Phase 1/2, open-label, dose escalation and dose expansion study designed to characterize the safety, tolerability, PK, immunogenicity, and preliminary antitumor activity of IBB0979 in previously treated patients with locally advanced or metastatic solid tumors.
Detailed Description
The study consists of Dose Escalation Phase, Dose Expansion Phase and Clinical Exploration Phase. Dose Escalation Phase：This phase is an open-label, non-randomized, multicenter, dose-escalation study. From the starting dose of 0.01 mg/kg, an accelerated titration combined with a "3+3" design will be adopted. Dose Expansion Phase：The application of Dose Expansion Phase can be discussed by investigator and sponsor based on data obtained in Dose Escalation Phase. This phase is an open-label, non-randomized, multicenter study. 6 patients with locally advanced or metastatic solid tumors are expected to be enrolled at DRDE. Each treatment cycle is defined as 21 days, patient may receive treatment until withdrawal or Treatment Discontinuation. Clinical Exploration Phase：After completing the dose escalation and expansion studies, the indication and study population can be discussed by the investigator and sponsor based on the efficacy and safety data that have been obtained.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female, 18 to 80 years old.
- •With histologically or cytologically confirmed locally advanced or metastatic solid malignant tumors, either (a) failed prior standard therapy, (b) for which no standard therapy exists, or (c) standard therapy is not considered appropriate.
- •There is at least one assessable tumor lesion in the Dose Escalation Phase and at least one measurable lesion in the Dose Expansion Phase According to RECIST 1.1 (tumor lesions located in the previous radiation therapy area or other local regional treatment area generally not be considered as measurable lesions, unless the lesion has progression or persists after three months of radiation therapy).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy ≥ 3 months.
- •Adequate organ functions:
- •Hematologic system (no transfusion or hematopoietic-stimulating factor therapy within 14 days): absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count (PLT) ≥ 90 × 109/L, hemoglobin (HGB) ≥ 90 g/L.
- •Liver function: total bilirubin (TBIL) ≤ 1.5 × the upper limit of normal values (ULN), except for Gilbert's syndrome; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × ULN, liver metastases or liver cancer patients with ALT and AST ≤ 5.0 × ULN.
- •Renal function: estimated creatinine clearance (Ccr) ≥ 50 mL/min (calculated according to the Cockcroft-Gault formula).
- •Thrombin function: international normalized ratio of prothrombin (INR) ≤ 1.5 × ULN, activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
Exclusion Criteria
- •Known hypersensitivity (≥ Grade 3) to recombinant proteins or any excipient contained in the drug or vehicle formulation for IBB
- •History of anti-tumor therapy (chemotherapy within 3 weeks or radiotherapy, biological therapy, endocrine therapy, targeted therapy within 4 weeks) prior to the initiation of investigational product administration, with the following exceptions:
- •Nitrosourea or mitomycin C should be within 6 weeks prior to the initiation of investigational product administration.
- •Oral fluoropyrimidines and small molecule targeted drugs should be within 2 weeks prior to the initiation of investigational product administration.
- •History of any un-marketed investigational product or therapy within 4 weeks prior to the initiation of investigational product administration.
- •History of major organ surgery (with exception of aspiration biopsy) or significant trauma within 4 weeks prior to the initiation of investigational product administration, or selective operation is required during the trial.
- •History of systemic corticosteroids (prednisone \>10 mg per day or equivalent) or other immune-suppressive drugs within the 14 days prior to the initiation of investigational product administration. Steroids for topical, ophthalmic, intraarticular, inhaled or nasal administration are allowed.
- •Treatment with immunomodulatory agents, including but not limited to thymosin, interleukin-2 and interferon within 14 days prior to the initiation of investigational product administration.
- •Vaccination with any live virus vaccine within 4 weeks prior to the initiation of investigational product administration.
- •History of prior allogeneic stem-cell or solid organ transplantation.
Arms & Interventions
Phase Ia - Dose escalation
The goal of the Dose Escalation Phase (Part A) is to initially characterize the safety and tolerability of IBB0979, and more specifically to describe the DLTs for each dose level studied and to define the MTD based on the frequency of the occurrence of DLTs in each cohort during the DLT evaluation period.
Intervention: IBB0979
Phase Ib - Dose extension
During the Dose Expansion Phase , patients will be enrolled to receive IBB0979 at the MTD established from the Dose Escalation Phase of the study.
Intervention: IBB0979
Phase IIa - Clinical Exploratory Stage
After finishing Phase 1, invesigators will discuss with the sponsor about how to carry out the Phase IIa due to the results acheived from Phase I.
Intervention: IBB0979
Outcomes
Primary Outcomes
Frequency of adverse events (AEs) and SAEs (Phase Ⅰ)
Time Frame: 3 months after end event visit
To investigate the safety characteristics.
Dose limiting toxicities (DLTs) (Phase Ⅰ)
Time Frame: 21 days after first dose
To determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D).
Objective response rate (ORR) in dose expansion (Phase Ⅱa)
Time Frame: Baseline through up to 1 years or until disease progression
To explore the clinical effectiveness. Tumor response based on RECIST 1.1.
Secondary Outcomes
- Pharmacokinetic (PK) Cmax (Phase Ⅰ)(Day1，2，3，4，6，8，11，14，17，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years)
- Pharmacokinetic (PK) AUC 0-t (Phase Ⅰ)(Day1，2，3，4，6，8，11，14，17，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years)
- Pharmacokinetic (PK) AUC 0-∞ (Phase Ⅰ)(Day1，2，3，4，6，8，11，14，17，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years)
- Pharmacokinetic (PK) Cmin (Phase Ⅰ)(Day1，2，3，4，6，8，11，14，17，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years)
- Pharmacokinetic (PK) Tmax (Phase Ⅰ)(Day1，2，3，4，6，8，11，14，17，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years)
- Pharmacokinetic (PK) CL (Phase Ⅰ)(Day1，2，3，4，6，8，11，14，17，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years)
- Pharmacokinetic (PK) Vd (Phase Ⅰ)(Day1，2，3，4，6，8，11，14，17，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years)
- Pharmacokinetic (PK) t1/2 (Phase Ⅰ)(Day1，2，3，4，6，8，11，14，17，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years)
- Pharmacokinetic (PK) λz (Phase Ⅰ)(Day1，2，3，4，6，8，11，14，17，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years)
- Pharmacokinetic (PK) Css,max (Phase Ⅰ)(Day1，2，3，4，6，8，11，14，17，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years)
- Pharmacokinetic (PK) Css,min (Phase Ⅰ)(Day1，2，3，4，6，8，11，14，17，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years)
- Pharmacokinetic (PK) Css,av (Phase Ⅰ)(Day1，2，3，4，6，8，11，14，17，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years)
- Pharmacokinetic (PK) AUCss (Phase Ⅰ)(Day1，2，3，4，6，8，11，14，17，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years)
- Pharmacokinetic (PK) CLss (Phase Ⅰ)(Day1，2，3，4，6，8，11，14，17，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years)
- Pharmacokinetic (PK) Vss (Phase Ⅰ)(Day1，2，3，4，6，8，11，14，17，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years)
- Objective response rate (ORR) in dose escalation (Phase Ⅰ)(Baseline through up to 1 years or until disease progression)
- Incidence of adverse events (AEs) and SAEs (Phase Ⅱa)(Baseline through up to 2 years or until disease progression)
- Pharmacokinetic (PK) R (Phase Ⅰ)(Day1，2，3，4，6，8，11，14，17，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years)
- Pharmacokinetic (PK) DF (Phase Ⅰ)(Day1，2，3，4，6，8，11，14，17，21 of each subsequent cycle (each cycle is 21 days), and at the End of Treatment visit, up to about 2 years)
- Incidence of adverse events (AEs) and SAEs (Phase Ⅰ)(3 months after end event visit)
- Immunogenicity of IBB0979(3 months after end event visit)
- Progression free survival (PFS) (Phase Ⅱa)(Baseline through up to 2 years or until disease progression)
- Overall survival (OS) (Phase Ⅱa)(Baseline through up to 2 years or until disease progression)
- Disease control rate (DCR) (Phase Ⅱa)(Baseline through up to 2 years or until disease progression)
- Immunogenicity of IBB0979 (Phase Ⅱa)(Baseline through up to 2 years or until disease progression)