A Phase 2, Open-label, Multicenter Study of IBI363 (PD1-IL2m) in Subjects with Advanced Solid Malignancies

Overview

IBI363 is an investigational bispecific antibody fusion protein developed by Innovent Biologics. It targets both the programmed death-1 (PD-1) receptor and interleukin-2 (IL-2) pathways, aiming to enhance anti-tumor immune responses. The U.S. Food and Drug Administration (FDA) has granted IBI363 fast track designation for the treatment of advanced unresectable or metastatic melanoma. (pharmaceutical-technology.com)

Mechanism of Action

IBI363 functions by simultaneously blocking the PD-1/PD-L1 pathway and activating the IL-2 pathway. The IL-2 component is engineered to retain affinity for the IL-2 receptor alpha (IL-2Rα) while reducing binding to IL-2Rβ and IL-2Rγ, thereby minimizing toxicity. This design selectively stimulates tumor-specific T cells expressing both PD-1 and CD25, enhancing anti-tumor activity while sparing bystander T cells and reducing the risk of autoimmunity. (1stoncology.com)

Efficacy

Melanoma: In a study involving 37 melanoma patients who had previously received immunotherapy, treatment with IBI363 at 1 mg/kg resulted in an objective response rate (ORR) of 29.7%, including one complete response and ten partial responses. The disease control rate (DCR) was 73%. (pharmaceutical-technology.com)

Non-Small Cell Lung Cancer (NSCLC): Among patients with squamous NSCLC who had undergone prior immunotherapy, IBI363 demonstrated an ORR of 35.1% and a DCR of 75.7%. (mdpile.com)

Colorectal Cancer (CRC): In a Phase I study of 68 advanced CRC patients, IBI363 achieved an ORR of 12.7%. Notably, in patients with PD-L1 combined positive score (CPS) ≥1, the ORR was 30.8%, and the DCR was 76.9%. (ascopubs.org)

Safety

IBI363 has demonstrated a manageable safety profile across various studies. In the CRC study, treatment-related adverse events (TRAEs) were reported in 91.2% of patients, with 23.5% experiencing grade ≥3 TRAEs. Common TRAEs included arthralgia (35.3%), anemia (32.4%), and pyrexia (22.1%). No treatment-related deaths were reported. (ascopubs.org)

Further Reading

• FDA grants fast track designation to Innovent’s IBI363
• First-in-class PD-1/IL-2 bispecific antibody fusion protein IBI363 in patients with advanced colorectal cancer: Safety and efficacy results from a phase I study
• Innovent Biologics Delivers Oral Presentation On Clinical Data Of IBI363 in Advanced Non-small Cell Lung Cancer And Other Solid Tumors At The 2024 ESMO Virtual Plenary

Last updated: Apr 2025

Inclusion Criteria:

1. Subjects have the ability to understand and give written informed consent for participation in this trial, including all evaluations and procedures as specified by this protocol;

2. Male or female subjects ≥ 18 years old;

3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1;

4. Anticipated life expectancy of ≥ 3 months;

Exclusion Criteria:

1. Inadequate bone marrow and organ function;

2. Received previous anti-tumor therapy: Any chemotherapy or targeted small molecule therapy (standard or investigational) within 2 weeks or 5 plasma half-lives. Received Nitrosoureas and mitomycin C within 6 weeks prior to first dose of study drug and during study; Any anti-cancer monoclonal antibody (mAb) within 4 weeks prior to first dose

3. Received live vaccines within 28 days prior to first administration of the study drug or plan on receiving any live vaccine during the study;

4. Has adverse reactions resulting from previous antitumor therapies, which have not resolved to Grade 0 or 1 toxicity according to NCI-CTCAE v5.0 (except for alopecia, fatigue, pigmentation and other conditions with no safety risk according to investigator' discretion) or baseline prior to the first dose of the study drug;

5. Undergone major surgery (Craniotomy, thoracotomy or laparotomy, and other surgery according to investigator' discretion, excluding needle biopsy) within 4 weeks prior to the first dose of the study drug, or who are expected to undergo major surgery during the study period, or who have severe unhealed wounds, trauma, ulcers, etc.