Genakumab Alone and in Combination With Tislelizumab in Patients With Advanced Malignant Solid Tumors

NCT05441046 | Unknown Phase 1

• 1 other identifier: Gensci048-ST-I
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I, multicenter, open-label dose escalation and expansion study to evaluate genakumab alone and in combination with tislelizumab in adult patients with advanced solid malignancies.

Conditions

Malignant Solid Tumors

Outcome Measures

Primary Outcomes (10)

• dose-limiting toxicities (DLTs)

  First cycle (21 days after first dose)

• adverse events (AEs) adverse events (AEs)

  through study completion, an average of 6 months

• serious adverse events (SAEs)

  through study completion, an average of 6 months

• PK parameters of genakumab: bioavailability

  Cycle 1 day 1/day 2/day 3/day 4/day 6/day 8/day 15, Cycle 2 day 1, Cycle 3 day 1, Cycle 4 day 1/day 2/day 3/day 4/day 6/day 8/day 15, and day 1 of every following cycles (every cycle is 21 days) through study completion, an average of 6 months

• PK parameters of genakumab: peak concentration (Cmax)

  Cycle 1 day 1/day 2/day 3/day 4/day 6/day 8/day 15, Cycle 2 day 1, Cycle 3 day 1, Cycle 4 day 1/day 2/day 3/day 4/day 6/day 8/day 15, and day 1 of every following cycles (every cycle is 21 days) through study completion, an average of 6 months

• PK parameters of genakumab: area under time-concentration curve (AUC)

  Cycle 1 day 1/day 2/day 3/day 4/day 6/day 8/day 15, Cycle 2 day 1, Cycle 3 day 1, Cycle 4 day 1/day 2/day 3/day 4/day 6/day 8/day 15, and day 1 of every following cycles (every cycle is 21 days) through study completion, an average of 6 months

• PK parameters of genakumab: t1/2

  Cycle 1 day 1/day 2/day 3/day 4/day 6/day 8/day 15, Cycle 2 day 1, Cycle 3 day 1, Cycle 4 day 1/day 2/day 3/day 4/day 6/day 8/day 15, and day 1 of every following cycles (every cycle is 21 days) through study completion, an average of 6 months

• PK parameters of genakumab: steady-state peak concentration

  Cycle 1 day 1/day 2/day 3/day 4/day 6/day 8/day 15, Cycle 2 day 1, Cycle 3 day 1, Cycle 4 day 1/day 2/day 3/day 4/day 6/day 8/day 15, and day 1 of every following cycles (every cycle is 21 days) through study completion, an average of 6 months

• PK parameters of genakumab: steady-state trough concentration

  Cycle 1 day 1/day 2/day 3/day 4/day 6/day 8/day 15, Cycle 2 day 1, Cycle 3 day 1, Cycle 4 day 1/day 2/day 3/day 4/day 6/day 8/day 15, and day 1 of every following cycles (every cycle is 21 days) through study completion, an average of 6 months

• PK parameters of genakumab: accumulation ratio

  Cycle 1 day 1/day 2/day 3/day 4/day 6/day 8/day 15, Cycle 2 day 1, Cycle 3 day 1, Cycle 4 day 1/day 2/day 3/day 4/day 6/day 8/day 15, and day 1 of every following cycles (every cycle is 21 days) through study completion, an average of 6 months

Secondary Outcomes (6)

• Pharmacodynamic: hsCRP

  Cycle 1 day 1/day 2/day 3/day 4/day 6/day 8/day 15, Cycle 2 day 1, Cycle 3 day 1, Cycle 4 day 1/day 2/day 3/day 4/day 6/day 8/day 15, and day 1 of every following cycles (every cycle is 21 days) through study completion, an average of 6 months

• Pharmacodynamic: total IL-1β

  Cycle 1 day 1/day 2/day 3/day 4/day 6/day 8/day 15, Cycle 2 day 1, Cycle 3 day 1, Cycle 4 day 1/day 2/day 3/day 4/day 6/day 8/day 15, and day 1 of every following cycles (every cycle is 21 days) through study completion, an average of 6 months

• Pharmacodynamic: free IL-1β

  Cycle 1 day 1/day 2/day 3/day 4/day 6/day 8/day 15, Cycle 2 day 1, Cycle 3 day 1, Cycle 4 day 1/day 2/day 3/day 4/day 6/day 8/day 15, and day 1 of every following cycles (every cycle is 21 days) through study completion, an average of 6 months

• Pharmacodynamic: IL-6

  Cycle 1 day 1/day 2/day 3/day 4/day 6/day 8/day 15, Cycle 2 day 1, Cycle 3 day 1, Cycle 4 day 1/day 2/day 3/day 4/day 6/day 8/day 15, and day 1 of every following cycles (every cycle is 21 days) through study completion, an average of 6 months

• Pharmacodynamic: IL-8

  Cycle 1 day 1/day 2/day 3/day 4/day 6/day 8/day 15, Cycle 2 day 1, Cycle 3 day 1, Cycle 4 day 1/day 2/day 3/day 4/day 6/day 8/day 15, and day 1 of every following cycles (every cycle is 21 days) through study completion, an average of 6 months

Study Arms (1)

Genakumab

EXPERIMENTAL

genakumab plus tislelizumab 200 mg

Drug: Genakumab

Interventions

Genakumab DRUG

genakumab plus tislelizumab 200 mg

Also known as: Tislelizumab

Genakumab

Eligibility Criteria

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

You may qualify if:

• Patients with advanced malignant tumors by histopathological diagnosis who do not have any acceptable standard treatments currently. Tumor types are specified as follows:
• Part I (Dose escalation): malignant solid tumors.
• Part II (Dose expansion):
• Cohort A: malignant solid tumors (excluding colorectal cancer and pancreatic cancer).
• Cohort B: colorectal cancer. Cohort C: pancreatic cancer.
• Patients who have provided informed consent prior to initiation of any study-specific activities/procedures.
• Age 18-75 years old.
• Life expectancy ≥ 12 weeks.
• Solid tumor with ≥ 1 measurable lesion that can be used to measure response according to RECIST v1.1. Index lesions must not be chosen from previously irradiated field unless there has been demonstrated disease progression in that lesion.
• Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Adequate organ function defined as follow:
• Hematological (without need for hematopoietic growth factor or transfusion support within 14 days prior to screening) Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Platelet count (PLT) ≥ 75 x 109/L Hemoglobin (HGB) ≥ 90 g/L
• Hepatic Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) OR ≤ 3 x ULN for patients with liver metastases or Gilbert syndrome Aspartate aminotransferase (AST) ≤ 2.5 x ULN OR ≤ 5 x ULN for patients with liver metastases Alanine aminotransferase (ALT) ≤ 2.5 x ULN OR ≤ 5 x ULN for patients with liver metastases
• Renal Serum creatinine ≤ 1.5 x ULN OR creatinine clearance ≥ 45 mL/min (according to the Cockcroft-Gault equation)
• Coagulation Activated thromboplastin time (aPTT) ≤ 1.5 x ULN International normalization ratio (INR) ≤ 1.5 x ULN If the patient is receiving anticoagulant therapy, the aPTT or INR must be in the therapeutic range of intended use of anticoagulants.

You may not qualify if:

• Patients with any of the following conditions may not be enrolled in the study:
• Prior treatment with IL-1β-targeting agents.
• Patients with previous severe allergic reactions to any investigational drugs or its components in this trial.
• Previous or current other types of malignancy diagnosed within 3 years, except as follows: basal cell or squamous cell skin cancer that has been cured, any type of carcinoma in situ that has been cured.
• Symptomatic central nervous system metastases. Patients with asymptomatic CNS metastases or patients who are radiologically and neurologically stable ≥ 2 weeks following CNS-directed therapy are eligible.
• Patients who have received any of the following treatments within 4 weeks or within 5 half-lives prior to the first dosing (whichever is shorter):
• Anti-tumor therapy (including chemotherapy, targeted therapy, immunotherapy, tumor artery embolization, and radiotherapy, excluding palliative radiotherapy);
• Any biological agents targeting immune system (e.g., TNF blockers, anakinra, rituximab, abatacept or tocilizumab, etc);
• Any live vaccines or live attenuated vaccines;
• Any other investigational drugs or another interventional clinical study (except for the following: patients who participate in an observational, non-interventional clinical study, or are in the follow-up period of an interventional clinical study).
• Major surgery or severe trauma within 4 weeks prior to the first dosing. Wounds and injuries must be fully recovered. Note: Video-assisted thoracoscopic surgery (VATS) and mediastinoscopy are not considered as major surgery. Patients who have received VATS or mediastinoscopy more than 2 weeks prior to the first dosing may be enrolled at the discretion of the investigator.
• Patients who have a cardiovascular clinical condition or symptom including:
• Unstable angina or myocardial infarction in the past 6 months;
• Coronary artery bypass grafting (CABG) in the past 6 months;
• Congestive heart failure (NYHA class 2);

Sponsors & Collaborators

• Changchun GeneScience Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

RECRUITING

MeSH Terms

Interventions

tislelizumab

Study Officials

• Xiangdong Cheng

  Zhejiang Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shuaishuai Zhang, MD

CONTACT

86 21 6087 1690; zhangshuaishuai@gensci-china.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: June 16, 2022
• First Posted: July 1, 2022
• Study Start: June 7, 2022
• Primary Completion: June 1, 2024
• Study Completion: March 1, 2025
• Last Updated: July 6, 2022

Record last verified: 2022-05

Locations

CN (1)