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

  • STATUS
    Recruiting
  • End date
    Mar 28, 2025
  • participants needed
    120
  • sponsor
    GeneScience Pharmaceuticals Co., Ltd.
Updated on 4 October 2022

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.

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.

Details
Condition Malignant Solid Tumors
Treatment Genakumab
Clinical Study IdentifierNCT05441046
SponsorGeneScience Pharmaceuticals Co., Ltd.
Last Modified on4 October 2022

Eligibility

Yes No Not Sure

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
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
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)
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)
Clinically significant malignant arrhythmia (e.g., persistent ventricular
tachycardia, clinically significant second- or third-degree atrioventricular
block without a pacemaker)
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
Patients with evidence of Human Immunodeficiency Virus (HIV) infection
Patients requiring systemic or local treatment with any immune modulating agent
in doses with systemic effects e.g., high dose oral or intravenous steroids (> 10
mg/d prednisone or its equivalents) or high dose methotrexate (> 15 mg weekly)
Topical, inhaled, local steroid use in doses that are not considered to cause
systemic effects are permitted
Patients with active or recurrent autoimmune disease, excluding: hypothyroidism
with replacement therapy, skin disease without need for systemic treatment
Patients with history of allogenic hematopoietic stem cell transplantation or
organ transplantation (except corneal transplantation)
Patients with any other medical condition which in the opinion of the
investigator places the patients at unacceptable risk for participation in
immunomodulatory therapy
Female patients who are pregnant or lactating, or have a positive pregnancy test result at
baseline
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