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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.
Full description
The study is divided into two parts:
Part I:
Part Ia: Two dose groups are planned, which are genakumab 200 mg, 300 mg. Genakumab is administered subcutaneously once every three weeks.
Part Ib: Three dose groups are planned, which are genakumab 100 mg plus tislelizumab 200 mg, genakumab 200 mg plus tislelizumab 200 mg, genakumab 300 mg plus tislelizumab 200 mg. Genakumab is administered subcutaneously once every three weeks. Tislelizumab is administered intravenously following genakumab on D1 of every cycle.
The study process of Part I includes the screening period (4 weeks), the observation period of dose-limiting toxicity (DLT) evaluation (defined as 3 weeks after first dosing), continuous dosing period (dosing once every 3 weeks until the discontinuation criteria are met), safety follow-up period after discontinuation (28±5 days after last dosing) and progression-free survival follow-up period after discontinuation (once every 6 weeks, until the progression-free survival follow-up endpoint).
Part II:
The sponsor and the investigator will choose one dose level as RP2D based on the totality of safety, PK, PD, and preliminary efficacy data from Part I. Additional 90 patients (30 patients for each cohort) will be treated at this dose level. The administration method is the same as that in Part I while without DLT observation.
Enrollment
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Inclusion criteria
Patients may be enrolled in the study only if they meet all of the following inclusion criteria:
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:
Female patients with the possibility of pregnancy: Agree to practice sexual abstinence or use effective methods of contraception from the time of signing the ICF until at least 6 months after the end of dosing. Male patients: Agree to practice abstinence or use effective contraception from the time of signing the ICF until at least 6 months after the end of dosing.
Patients who have recovered from the toxic effects of the last treatment (CTCAE ≤ grade 1, except for special circumstances such as "alopecia") before the first dosing.
Exclusion criteria
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):
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:
Uncontrolled diabetes or hypertension defined by the investigator.
History of interstitial lung disease.
Active or recurrent liver disease, including hepatitis B, hepatitis C, and liver cirrhosis.
Patients with active pulmonary tuberculosis found by medical history or CT examination, or with a history of active pulmonary tuberculosis infection before enrollment (Patients who have received anti-tuberculosis treatment and further examinations confirm that there is no evidence of active infection are eligible.).
Patients with active infection requiring systematic treatment within 2 weeks prior to the first dosing (Patients with skin infection requiring only topical treatment are eligible.).
Patients with suspected or proven immunocompromised state, including:
Female patients who are pregnant or lactating, or have a positive pregnancy test result at baseline.
Primary purpose
Allocation
Interventional model
Masking
120 participants in 1 patient group
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Central trial contact
Shuaishuai Zhang, MD
Data sourced from clinicaltrials.gov
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