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

Overview

IBI363 (Takeda code TAK-928) is an investigational PD-1/IL-2α-biased bispecific antibody fusion protein developed by Innovent Biologics. It is in clinical development for several solid tumors, particularly non-small-cell lung cancer (NSCLC), melanoma and microsatellite-stable/proficient mismatch-repair colorectal cancer (MSS/pMMR CRC). Takeda and Innovent are jointly developing it globally. Published evidence currently consists mainly of early-phase, single-arm trials and conference abstracts rather than randomized efficacy results. (takeda.com)

Mechanism of action

IBI363 combines PD-1 checkpoint blockade with an α-biased IL-2 signal. By binding PD-1 and delivering IL-2 signaling in cis, it is intended to preferentially expand and reinvigorate exhausted, tumor-specific PD-1-positive T cells while limiting nonspecific systemic IL-2 stimulation. (ascopubs.org)

Efficacy

• Previously treated NSCLC: In an updated phase 1 analysis of 136 patients, the 3-mg/kg-every-three-weeks cohort had median progression-free survival of 10.1 months in squamous NSCLC and 4.2 months in EGFR-wild-type adenocarcinoma. Median overall survival was 18.2 and 15.2 months, respectively. Earlier response-evaluable results at this dose showed objective response rates of 43.3% in squamous disease and 28.0% in adenocarcinoma. These were nonrandomized dose cohorts, so comparisons with standard treatment remain uncertain. (ascopubs.org)
• Acral or mucosal melanoma after immunotherapy: Among 87 evaluable patients, the objective response rate was 26.4%, including one complete response; disease control was 64.4%. At the 1-mg/kg-every-two-weeks dose, median response duration was 14.0 months and median progression-free survival was 5.7 months. (ascopubs.org)
• Advanced predominantly MSS/pMMR CRC: Objective response rates were 12.7% with IBI363 alone and 23.5% with bevacizumab. Among 31 combination-treated patients without liver metastases, the response rate was 38.7%, disease-control rate 83.9%, and median progression-free survival 9.6 months. (ascopubs.org)
• First-line NSCLC combination: Preliminary phase 1 results for IBI363 plus platinum-doublet chemotherapy reported response rates of 57.9%–86.4%, depending on dose cohort; progression-free-survival data were immature. (asco.org)

Safety

Across studies, frequently reported adverse events included arthralgia, rash and anemia. In the 136-patient NSCLC phase 1 analysis, 48.5% experienced grade 3 or higher treatment-emergent adverse events; 8.1% discontinued treatment because of an adverse event, and one death was considered treatment-related. (asco.org)

In melanoma, grade 3 or higher treatment-emergent adverse events occurred in 29.7% of patients; one treatment-related death from sepsis was reported. In CRC, grade 3 or higher treatment-related adverse events occurred in 23.5% with monotherapy and 30.1% with the bevacizumab combination. (ascopubs.org)

Further reading

• Updated phase 1 NSCLC results, ASCO 2026
• Phase 1 NSCLC response analysis, ASCO 2025
• Acral and mucosal melanoma results
• Colorectal cancer monotherapy and bevacizumab-combination results
• Review of PD-1/IL-2 bispecific agents

Last updated: Sep 2026

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.