Last updated: July 1, 2026 — per-NCT detail accordions added (post-ASCO 2026)
Ivonescimab (development code AK112; brand name Yiruixi / 依沃西单抗 in China; partner code SMT112 from Summit Therapeutics outside Greater China) is a tetravalent bispecific antibody developed by Akeso Biopharma. It simultaneously blocks PD-1 (an immune checkpoint on T cells) and VEGF (vascular endothelial growth factor, the angiogenesis signal that tumors use to grow blood vessels).
Mechanism of action:Combining checkpoint blockade with anti-angiogenic therapy is established (e.g., atezolizumab + bevacizumab in HCC, pembrolizumab + bevacizumab in cervical cancer). Ivonescimab's distinction is doing both with a single molecule designed for cooperative binding: VEGF is abundant in the tumor microenvironment, and its presence enhances the avidity of the PD-1 binding arm at the same site — concentrating activity inside tumors versus systemic exposure. The clinical rationale is to combine the two mechanisms with potentially better tumor-selectivity than separate-molecule combinations.
Regulatory status:Ivonescimab is the world's first approved bispecific PD-1/VEGF antibody. China's NMPA approval timeline:
U.S. FDA: Summit Therapeutics submitted a Biologics License Application for ivonescimab + chemotherapy in 2L+ EGFR-mutated non-squamous NSCLC after TKI progression. FDA has accepted the BLA for filing with a PDUFA goal action date of November 14, 2026. Submission based on the global Phase 3 HARMONi trial. Note on global Phase 3 HARMONi-3 (ivonescimab + chemo vs pembrolizumab + chemo in 1L NSCLC): in Q2 2026, the squamous cohort's planned interim PFS analysis did not meet the threshold for statistical significance; the independent data monitoring committee recommended the trial continue as planned and remain double-blinded. The overall study readout is still pending.
The pattern across the 2026 Phase 3 program is consistent: ivonescimab is being tested directly against the current standard of care in each indication — pembrolizumab in NSCLC and HNSCC, bevacizumab in CRC — not added to it. The ASCO 2026 wrap-up highlighted the breadth of this 1L+ expansion.
Ivonescimab has become a major investigational backbone in SCLC. The Phase 3 consolidation program is the most advanced:
The approved indication in China and the focus of the global FDA-registration program. NSCLC carries the heaviest 1L head-to-head footprint against pembrolizumab:
Approved in China for 1L HCC (+ lenvatinib); active expansion into TACE combinations and earlier-line settings:
Including a notable head-to-head Phase 3 against bevacizumab + chemo (the current 1L anti-angiogenic standard):
Phase 3 1L combination + perioperative/adjuvant settings:
Including a head-to-head Phase 3 against pembrolizumab (the current 1L IO standard for HNSCC):
For rare or histology-orphan cancers without dedicated ivonescimab trials, a multi-tumor basket Phase 2 offers cohort-based access:
Showing pivotal Phase 3 trials plus indication-cluster summaries. The full set of 62 recruiting interventional studies (plus 58 not-yet-recruiting in setup) includes additional investigator-initiated combinations not listed above. View the latest on ClinicalTrials.gov.
Detailed accordions for five high-visibility ivonescimab (AK112) Phase 3 trials currently recruiting. Each accordion summarizes the trial's setting, eligibility highlights, and a direct route into ClinTrialFinder's patient-matching wizard. All entries cross-checked against the live ClinicalTrials.gov record on June 14, 2026.
Official title: A Randomized, Controlled, Multicenter Phase 3 Study of AK112 in Combination With AK117 Versus Pembrolizumab as First Line Treatment for a Programmed Cell Death-ligand 1 (PD-L1) Positive Population With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)
Sponsor: Akeso
Phase: 3 | Status: RECRUITING | Setting: 1L recurrent or metastatic HNSCC (oropharynx, oral cavity, hypopharynx, larynx), PD-L1–positive, considered incurable by local therapy
Why this trial matters: Direct Phase 3 head-to-head against pembrolizumab + the global 1L IO standard in HNSCC. The experimental arm pairs the ivonescimab PD-1/VEGF bispecific with AK117 (anti-CD47, "don't-eat-me" macrophage checkpoint), testing whether layered checkpoint blockade can displace pembrolizumab in front-line R/M HNSCC. Planned enrollment 510.
Eligibility highlights: Age ≥ 18 (per protocol), ECOG 0–1, life expectancy ≥ 3 months, histologically confirmed R/M HNSCC of oropharynx / oral cavity / hypopharynx / larynx, oropharyngeal cases require HPV status, no prior systemic treatment for R/M HNSCC, at least one measurable non-cerebral lesion. Full eligibility on ClinicalTrials.gov.
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External reference: View NCT06601335 on ClinicalTrials.gov
Official title: A Randomized, Double-blinded, Multiregional Phase 3 Study of Ivonescimab Versus Pembrolizumab for the First-line Treatment of Metastatic Non-small Cell Lung Cancer in Patients with High PD-L1 Expression
Sponsor: Summit Therapeutics
Phase: 3 | Status: RECRUITING | Setting: 1L Stage IV (metastatic) NSCLC, squamous or non-squamous, PD-L1 TPS > 50% by 22C3 IHC
Why this trial matters: The second 1L NSCLC monotherapy head-to-head against pembrolizumab after HARMONi-2 (which showed ivonescimab PFS superiority in 1L PD-L1–positive NSCLC in China). HARMONi-7 is the global, multiregional confirmatory readout that defines whether ivonescimab becomes a pembrolizumab alternative in front-line high-PD-L1 lung cancer. Planned enrollment 780.
Eligibility highlights: Age ≥ 18, ECOG 0–1, life expectancy ≥ 3 months, metastatic Stage IV NSCLC (squamous or non-squamous), high PD-L1 TPS > 50% by 22C3 IHC, at least one measurable non-cerebral lesion per RECIST 1.1, no prior systemic therapy for metastatic disease. Full eligibility on ClinicalTrials.gov.
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External reference: View NCT06767514 on ClinicalTrials.gov
Official title: A Randomized, Active-Controlled, Double-blind, Multicenter, Phase 3 Clinical Study of Ivonescimab in Combination With mFOLFOX6 (Oxaliplatin, Leucovorin and 5-Fluorouracil) versus Bevacizumab in Combination with FOLFOX for the First-line Treatment of Metastatic Colorectal Cancer (HARMONi-GI3)
Sponsor: Summit Therapeutics
Phase: 3 | Status: RECRUITING | Setting: 1L metastatic colorectal cancer, microsatellite-stable (MSI-H / dMMR excluded), BRAF V600E excluded
Why this trial matters: The first direct Phase 3 head-to-head of a PD-1/VEGF bispecific against bevacizumab, the current 1L anti-angiogenic backbone in mCRC. If HARMONi-GI3 is positive, ivonescimab could displace bevacizumab in the FOLFOX backbone for MSS mCRC — a tumor type where checkpoint monotherapy has historically failed outside MSI-high disease. Planned enrollment 600.
Eligibility highlights: ECOG 0–1, life expectancy ≥ 6 months, histologically or cytologically confirmed metastatic CRC, no prior systemic therapy for metastatic CRC, at least one measurable non-cerebral lesion. Key exclusions: MSI-H / dMMR, BRAF V600E mutation, significant GI obstruction, ascites requiring paracentesis. Full eligibility on ClinicalTrials.gov.
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External reference: View NCT07228832 on ClinicalTrials.gov
Official title: A Randomized, Controlled, Multi-center Phase III Clinical Study of AK112 Plus Nab-paclitaxel Versus Placebo Plus Nab-paclitaxel as First-line Treatment for Locally Advanced Unresectable or Metastatic Triple-negative Breast Cancer
Sponsor: Akeso
Phase: 3 | Status: RECRUITING | Setting: 1L inoperable locally advanced or metastatic triple-negative breast cancer (ER−, PR−, HER2−), no prior systemic therapy for advanced disease
Why this trial matters: Moves the PD-1/VEGF bispecific into the same 1L mTNBC backbone setting where datopotamab deruxtecan (Datroway) received FDA approval on May 22, 2026. A positive readout would expand the 1L mTNBC IO toolkit beyond the pembrolizumab + chemo paradigm (which requires PD-L1 CPS ≥ 10). Planned enrollment 416.
Eligibility highlights: Age 18–75, ECOG 0–1, life expectancy ≥ 3 months, histologically confirmed unresectable LA or metastatic TNBC (ER/PR/HER2 negative), no prior systemic treatment for advanced breast cancer, suitable for taxane-based monotherapy. Full eligibility on ClinicalTrials.gov.
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External reference: View NCT06767527 on ClinicalTrials.gov
Official title: A Multicenter, Randomized, Double-blind, Phase III Clinical Study of Comparing the Efficacy and Safety of AK112 as Consolidation Treatment for Patients With Limited Stage Small-cell Lung Cancer Who Have Not Progressed Following Concurrent Chemoradiation Therapy
Sponsor: Akeso
Phase: 3 | Status: RECRUITING | Setting: Consolidation after concurrent chemoradiation in limited-stage SCLC (Stage I–III, T-any, N-any, M0, AJCC staging) patients who have not progressed
Why this trial matters: Positions ivonescimab directly against the durvalumab/ADRIATIC paradigm in limited-stage SCLC consolidation. ADRIATIC (durvalumab) established 30+ months overall survival in LS-SCLC consolidation in 2024; this Phase 3 tests whether the PD-1/VEGF bispecific can match or exceed that bar. Planned enrollment 560.
Eligibility highlights: Age ≥ 18, ECOG 0–1, life expectancy ≥ 3 months, histologically or cytologically confirmed SCLC, documented limited-stage SCLC (Stage I–III, AJCC), prior concurrent chemoradiation completed without progression. Full eligibility on ClinicalTrials.gov.
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External reference: View NCT07010263 on ClinicalTrials.gov
Ivonescimab trials use a mix of standard immunotherapy biomarkers and indication-specific enrichment:
What is ivonescimab?
Ivonescimab (development code AK112, brand name Yiruixi / 依沃西单抗 in China; partner code SMT112 from Summit Therapeutics outside Greater China) is a tetravalent bispecific antibody that simultaneously blocks PD-1 (immune checkpoint) and VEGF (tumor angiogenesis). Developed by Akeso Biopharma; Summit Therapeutics holds rights outside Greater China. China's NMPA has approved it for several NSCLC indications since May 2024. The U.S. FDA has accepted Summit's BLA for ivonescimab + chemotherapy in EGFR-mutated NSCLC post-TKI; PDUFA goal action date November 14, 2026.
How is ivonescimab different from combining pembrolizumab and bevacizumab?
The therapeutic concept is similar — block PD-1 and VEGF together — but the design is different. Ivonescimab is a single tetravalent molecule with cooperative binding: VEGF abundance in the tumor microenvironment increases the avidity of PD-1 engagement at the same site, concentrating activity inside tumors. The HARMONi-2 Phase 3 trial in China showed ivonescimab monotherapy demonstrated superior progression-free survival compared with pembrolizumab monotherapy in 1L PD-L1-positive NSCLC — the first single agent to beat pembrolizumab in 1L NSCLC. Global head-to-head confirmation is in ongoing Phase 3 trials.
Is ivonescimab (AK112) the same as PM8002?
No. Ivonescimab (AK112) and PM8002 (also known as BNT327) are two different PD-1/VEGF bispecific antibodies from two different companies. Ivonescimab is developed by Akeso Biopharma (Summit Therapeutics outside Greater China). PM8002 is developed by Biotheus Inc. (now BioNTech, which acquired Biotheus in late 2024). Both target PD-1 and VEGF simultaneously but are independent molecules with distinct molecular designs, separate clinical programs, and separate trial registrations. If you are searching for PM8002 or BNT327 trials (including NCT06419621 in metastatic TNBC), those are PM8002 trials, not ivonescimab trials. Both drug classes are emerging as important options in NSCLC, TNBC, and other tumor types, and head-to-head comparisons may eventually be performed.
What ivonescimab trials are currently recruiting?
62 recruiting interventional ivonescimab trials as of July 2026 (plus 58 not-yet-recruiting in setup), including 10 Phase 3 pivotal studies. Indication leaders include NSCLC (HARMONi-7 vs pembrolizumab in 1L high PD-L1; + docetaxel post-IO Phase 3), SCLC (limited-stage consolidation Phase 3), colorectal (HARMONi-GI3 Phase 3 vs bevacizumab; 1L chemo Phase 3), triple-negative breast (1L nab-paclitaxel Phase 3), HCC, head and neck (R/M HNSCC Phase 3 vs pembrolizumab + AK117; ILLUMINE Phase 3 with ligufalimab), pancreatic, cervical and gynecologic, sarcoma, gastric/GEJ, plus mesothelioma, RCC, nasopharyngeal, bladder, and rare-tumor basket access (NCT06683846). Most trials are sponsored or led from China; Summit is running additional global Phase 3 trials (HARMONi-3, HARMONi-7, HARMONi-GI3, ILLUMINE) outside Greater China.
What are the main side effects of ivonescimab?
Side effects combine immune-related events (PD-1) and anti-angiogenic events (VEGF). Immune-related: hypothyroidism, skin rash, fatigue, immune-mediated colitis, hepatitis, pneumonitis. Anti-angiogenic: hypertension (most common Grade 3+), proteinuria, bleeding (typically minor; serious hemorrhage and pulmonary embolism are rare but require monitoring, especially in squamous histologies), delayed wound healing. Combined profile in published Phase 3 trials has been broadly manageable.
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