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

Overview

IBI363 is an investigational PD‑1/IL‑2α‑biased bispecific antibody fusion protein from Innovent Biologics being developed for multiple solid tumors, including melanoma, non–small cell lung cancer (NSCLC), and colorectal cancer (CRC). Early-phase clinical results have been presented at ASCO and ESMO, and a phase 3 program in immunotherapy‑resistant squamous NSCLC is planned following FDA IND clearance. (ascopubs.org)

Mechanism of action

• Dual function: blocks the PD‑1/PD‑L1 pathway and delivers an IL‑2 agonist signal biased toward IL‑2Rα (CD25) while attenuating IL‑2Rβ/γ engagement, aiming to activate PD‑1+CD25+ tumor‑specific T cells in tumors and reduce systemic IL‑2–related toxicities. (prnewswire.com)
• Preclinical work in Nature Cancer supports IL‑2Rα‑biased agonism as a strategy to invigorate PD‑1+CD25+ CD8+ tumor‑infiltrating T cells and synergize with PD‑1 blockade, with improved efficacy and safety versus “not‑α” IL‑2 approaches. (nature.com)

Efficacy

Melanoma (IO‑pretreated acral/mucosal and other subtypes; Phase 1) - ASCO 2024 abstract (NCT05460767): among 57 evaluable patients with advanced melanoma, ORR 28.1% (1 CR, 15 PR), DCR 71.9%; in the 1 mg/kg Q2W cohort with prior IO (n=25), ORR 32.0%. Data were immature for DoR/PFS at that cut. (ascopubs.org)

Other solid tumors (Phase 1, basket) - ASCO 2024 abstract “other solid tumors”: in 18 evaluable patients (BTC, HNSCC, cervical, ovarian), overall ORR 22.2% and DCR 77.8%; confirmed PRs reported across several tumor types (e.g., BTC, HNSCC, cervical, ovarian). (ascopubs.org)

NSCLC (immunotherapy‑resistant; Phase 1 PoC) - ASCO 2025 update (NCT05460767), squamous NSCLC:
- 1–1.5 mg/kg cohorts (n=28): ORR 25.9%, DCR 66.7%, median PFS 5.5 months, median OS 15.3 months.
- 3 mg/kg Q3W cohort (n=31): ORR 36.7%, DCR 90.0%, median PFS 9.3 months; median OS not reached (12‑month OS 70.9%). (biospace.com)

Colorectal cancer (largely MSS/pMMR; Phase 1) - Monotherapy (NCT05460767): in 68 treated patients, median OS 16.1 months with 20.1‑month median follow‑up; in the 1 mg/kg Q2W subset (n=22), confirmed ORR 13.6%. (prnewswire.com) - Combination with bevacizumab (NCT06717880): among 73 patients, cORR 15.1%, DCR 61.6%, median PFS 4.7 months overall; in those without liver metastasis (n=32), cORR 31.3% and median PFS 7.4 months; at 3 mg/kg Q3W + bevacizumab (n=31), cORR 19.4% and median PFS 5.6 months. (biospace.com)

Regulatory/development status - China NMPA Breakthrough Therapy Designation for first‑line unresectable/metastatic mucosal or acral melanoma; pivotal study versus pembrolizumab initiated in 2025. (prnewswire.com) - FDA cleared an IND to start a global phase 3 (MarsLight‑11) in immunotherapy‑resistant squamous NSCLC. (cancernetwork.com)

Safety

• Melanoma Phase 1 (ASCO 2024): treatment‑emergent AEs in 94%; grade ≥3 TEAEs 23.9% and grade ≥3 TRAEs 17.9%; common AEs (≥20%) included arthralgia (34.3%), hyperthyroidism (29.9%), anemia (25.4%); 1.5% discontinued due to TEAEs; no treatment‑related deaths reported. (ascopubs.org)
• Across CRC combination cohorts with bevacizumab, safety was described as manageable without new signals; detailed AE rates not fully enumerated in public summaries. (biospace.com)
• Mechanistically, the IL‑2Rα‑biased and PD‑1‑directed delivery design aims to narrow systemic IL‑2 toxicity while activating intratumoral PD‑1+CD25+ T cells. (prnewswire.com)

Further reading

• ASCO 2024 abstract (melanoma Phase 1): First‑in‑class PD‑1/IL‑2 bispecific antibody fusion protein IBI363 in patients with advanced melanoma. (ascopubs.org)
• ASCO 2024 abstract (other solid tumors Phase 1): IBI363 in biliary tract, HNSCC, cervical, ovarian cancer. (ascopubs.org)
• Nature Cancer (2023): IL‑2Rα‑biased agonist enhances antitumor immunity by invigorating tumor‑infiltrating CD25+CD8+ T cells. (nature.com)
• ASCO 2025 updates (press summaries): NSCLC Phase 1 PoC results; CRC monotherapy and bevacizumab combination datasets. (biospace.com)
• Regulatory/development news: FDA IND clearance for phase 3 in squamous NSCLC; China NMPA Breakthrough Therapy Designation in melanoma. (cancernetwork.com)

Notes and caveats: Most public efficacy/safety data are from conference abstracts and company communications; peer‑reviewed clinical publications for IBI363 were not identified as of October 7, 2025. Where possible, primary ASCO abstracts and the Nature Cancer preclinical study are cited. (ascopubs.org)

Last updated: Oct 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.