Clinical trial NCT04085185: A Study Evaluating the Safety, Tolerability, and Initial Efficacy of IBI110 in Subjects With Advanced Malignant Tumors
Official title: A Phase 1a, Open-label, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Initial Efficacy of IBI110 in Subjects With Advanced Malignant Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Malignancies
Lead sponsor: Innovent Biologics (Suzhou) Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2019-09-11
Enrollment: 268
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, dose escalation, Phase I study to evaluate the safety, tolerability, pharmacokinetics and efficacy of IBI110 in subjects with advanced malignancies.


Eligibility criteria: Inclusion Criteria:

1. Able to understand and willing to sign the ICF.
2. Adults 18 years of age or older.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Life expectancy at least 12 weeks.
5. Adequate organ and bone marrow function.
6. Histologically/cytologically confirmed, locally advanced unresectable or metastatic solid tumors and lymphomas that are refractory to standard therapy, or for which no standard therapy exists.
7. Measurable disease according to RECIST Version 1.1 in solid tumor.
8. Subjects (women of child-bearing potential and males) must be willing to use viable contraception method that is deemed effective by the investigator throughout the treatment period and for at least three months following the last dose of study drug. Postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential.

Exclusion Criteria:

1. Previous exposure to any anti-lag-3 antibody.
2. Participate in another interventional clinical study, except for the observational (non-interventional) clinical study or the survival follow-up phase of the interventional study.
3. Any investigational drugs received within 4 weeks prior to the first study treatment.
4. Receive the last dose of anti-tumor therapy within 4 weeks before the first dose of study therapy.
5. Immunosuppressive drugs were used within 4 weeks prior to the first administration of the study drug.
6. Medication requiring long-term systemic hormones or any other immunosuppression therapy.
7. Major surgical procedures (craniotomy, thoracotomy, or laparotomy) or unhealed wounds, ulcers, or fractures were performed within 4 weeks prior to the first dose of study therapy.
8. There were unrecovered toxicity (excluding hair loss or fatigue) according to NCI CTCAE v5.0 induced by previous antitumor therapy (24 weeks before the first dose of study), and there were unrecovered immune-related adverse events (irAE) associated with immunotherapy.
9. Previous immunotherapy, such as anti-PD-1 / anti-PD-L1 antibody or anti-CTLA4 antibody, was discontinued due to the presence of \> grade 3 irAE.
10. Primary central nervous system (CNS) malignancy, or untreated/active CNS metastases, or leptomeningeal disease.
11. History of autoimmune disease , present active autoimmune disease or inflammatory diseases
12. Present or history of pulmonary diseases such as interstitial pneumonia, pneumoconiosis, drug-related pneumonia, pulmonary fibrosis, active pulmonary infection, severely impaired pulmonary function.
13. Positive human immunodeficiency virus (HIV) test.
14. Active hepatitis B or C, or tuberculosis.
15. History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation. 16. History of gastrointestinal perforation and/or fistula at 6 months prior to study inclusion.

17.Hydrothorax, ascites, and pericardial effusion with clinical symptoms requiring drainage.

18.Known history of hypersensitivity to any components of the IBI110 or Sintilimab.

19.Uncontrolled complications of disease.

20.Other acute or chronic illness, mental illness, or abnormal laboratory test values that may increase the risk of study participation or administration of study drugs, or interfere with the interpretation of study results.

21.History of other primary malignancies. 22. Pregnant or nursing females.

Primary outcomes:
measure: Number of subjects with AEs and SAEs
timeFrame: up to 2 years after enrollment
measure: Percentage of Participants with Dose-Limiting Toxicities (DLTs)
timeFrame: From Baseline to the end of Cycle 1
Secondary outcomes:
measure: Pharmacokinetics: AUC
timeFrame: up to 2 years after enrollment
measure: Pharmacokinetics: Cmax
timeFrame: up to 2 years after enrollment
measure: Immunogenicity: Percentage of ADA positive subjects
timeFrame: up to 2 years after enrollment
measure: Preliminary anti-tumor activity of IBI110 (Objective Response Rate)
timeFrame: up to 2 years after enrollment
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
Study officials:
References: