IBI363

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