A Study Evaluating the Safety, Tolerability, and Initial Efficacy of IBI110 in Subjects With Advanced Malignant Tumors

Innovent Biologics

Status and phase: Enrolling; Phase 1

Conditions: Advanced Malignancies

Treatments: Drug: IBI110; Drug: IBI110+ Sintilimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04085185

CIBI110A101

Details and patient eligibility

About

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.

Enrollment: 268 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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268 participants in 4 patient groups

Phase Ia Dose-Escalation Stage:IBI110

Experimental group

Description:

Participants will be treated with escalating doses of IBI110 to determine the MTD.

Treatment:

Drug: IBI110

Drug: IBI110

Phase Ia Expansion Stage:IBI110

Experimental group

Description:

Participants will be enrolled in the expansion stage to better characterize the safety, tolerability, PK variability, and preliminary efficacy of IBI110 in different cancer types.

Treatment:

Drug: IBI110

Drug: IBI110

Phase Ib Dose-Escalation Stage:IBI110+ Sintilimab

Experimental group

Description:

Participants will be treated with escalating doses of IBI110 in combination with a fixed dose of Sintilimab to determine the MTD.

Treatment:

Drug: IBI110+ Sintilimab

Drug: IBI110+ Sintilimab

Phase Ib Expansion Stage:IBI110+ Sintilimab

Experimental group

Description:

Participants will be enrolled in the expansion stage to better characterize the safety, tolerability, PK variability, and preliminary efficacy of IBI110 in combination with Sintilimab in different cancer types.

Treatment:

Drug: IBI110+ Sintilimab

Drug: IBI110+ Sintilimab