62 Ivonescimab (AK112) Clinical Trials Recruiting Now (September 2026): NSCLC, SCLC, HCC, Colorectal, TNBC — PD-1/VEGF Bispecific (HARMONi-7, HARMONi-GI3, ILLUMINE)
Last updated: September 3, 2026 — per-NCT detail accordions added (post-ASCO 2026)
📍 Post-ASCO 2026 update (June 9, 2026): ASCO 2026 (June 5–9, Chicago) closes today. The ASCO 2026 takeaway for ivonescimab was the breadth of the 1L+ Phase 3 footprint Akeso and Summit are running directly against the current pembrolizumab-based standard — not on top of it. The drug already beat pembrolizumab on PFS in 1L PD-L1-positive NSCLC (HARMONi-2, late 2024). The next 12–18 months of Phase 3 readouts — HARMONi-7 (NSCLC vs pembrolizumab, high PD-L1), 1L TNBC, 1L mCRC, limited-stage SCLC consolidation, R/M HNSCC vs pembrolizumab + AK117 — will define whether ivonescimab becomes a global pembrolizumab alternative.
Quick answers for ivonescimab (AK112) NCT searches:
- NCT06145308 — Ivonescimab is Cohort 12. This is the Cancer Hospital, Chinese Academy of Medical Sciences (Beijing) 20-cohort precision-therapy basket study in recurrent / metastatic salivary gland carcinoma (Phase 2, RECRUITING). Ivonescimab + investigator-choice platinum doublet is Cohort 12; cadonilimab is Cohort 14. Eligibility is salivary gland carcinoma with the molecular subtype assigned to your cohort — not ivonescimab-specific. Full cohort allocation rules ↓
- NCT06419621 — NOT ivonescimab. This is a Phase 3 study of PM8002 (also BNT327), a different PD-1 / VEGF bispecific antibody developed by Biotheus (acquired by BioNTech in late 2024), in combination with nab-paclitaxel as 1L treatment in inoperable LA / metastatic triple-negative breast cancer. PM8002 and ivonescimab share a mechanism class but are independent molecules from different companies. The ivonescimab 1L mTNBC analogue is NCT06767527. Full PM8002 vs ivonescimab disambiguation ↓
- NCT06601335 — Yes, ivonescimab. Phase 3, RECRUITING. AK112 (ivonescimab) + AK117 (anti-CD47) vs pembrolizumab + placebo as 1L treatment in PD-L1-positive (CPS ≥ 1) recurrent / metastatic head and neck squamous cell carcinoma (R/M HNSCC). Akeso-sponsored, study ID AK117-302. View on ClinicalTrials.gov.
- NCT06530251 — Yes, ivonescimab. Phase 1b/2, RECRUITING. AK112 (ivonescimab) in combination therapies for advanced hepatocellular carcinoma (HCC); 2-part design (Ph1b safety / RP2D, Ph2 efficacy). Akeso-sponsored, study ID AK112-209. View on ClinicalTrials.gov.
About Ivonescimab
Drug profile:
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:
- May 2024: 1L EGFR-TKI-refractory EGFR-mutant NSCLC (HARMONi-A Phase 3)
- September 2024: 1L PD-L1-positive NSCLC (HARMONi-2 Phase 3 — ivonescimab monotherapy superior to pembrolizumab monotherapy on PFS, the first single agent to beat pembrolizumab in 1L NSCLC)
- 2025: additional NSCLC indications and 1L hepatocellular carcinoma (+ lenvatinib)
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.
Active Research Directions in 2026
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.
- Lung cancer is the dominant focus — SCLC (15 recruiting trials, the largest single indication for ivonescimab) and NSCLC (11) together account for ~37% of the active pipeline. Multiple Phase 3 trials confirming HARMONi-A / HARMONi-2 readouts, plus new combinations and earlier-line maintenance settings.
- NSCLC 1L head-to-head against pembrolizumab — HARMONi-7 (NCT06767514) tests ivonescimab vs pembrolizumab in 1L metastatic NSCLC with high PD-L1, the second 1L head-to-head against pembrolizumab after HARMONi-2.
- NSCLC post-IO progression — ivonescimab + docetaxel in advanced NSCLC after 1L progression (NCT06928389, Phase 3), addressing the post-IO chemotherapy setting.
- SCLC consolidation — ivonescimab as consolidation in limited-stage SCLC after concurrent chemoradiation (NCT07010263, Phase 3), positioning the drug against the durvalumab/ADRIATIC paradigm in limited-stage disease.
- HCC + lenvatinib + ivonescimab — building on the 2025 China approval for 1L HCC, multiple Phase 2/3 combination trials expand to TACE and earlier-line settings.
- Colorectal cancer — 7 trials including 1L Phase 3 chemo-IO combinations (NCT06951503) and the head-to-head Phase 3 against bevacizumab in metastatic CRC (HARMONi-GI3, NCT07228832).
- Triple-negative breast cancer (TNBC) — Phase 3 1L ivonescimab + nab-paclitaxel (NCT06767527) and Phase 2 perioperative/adjuvant studies.
- Head & neck squamous cell carcinoma (HNSCC) — head-to-head Phase 3 against pembrolizumab in 1L R/M HNSCC (NCT06601335, with anti-CD47 AK117) plus ILLUMINE (NCT07264075, with or without ligufalimab vs pembrolizumab).
- Pancreatic cancer Phase 3 — ivonescimab + chemo ± AK117 (anti-CD47) in 1L mPDAC (NCT06953999).
- Rare-tumor basket access — the Fudan multi-tumor Phase 2 (NCT06683846) lists ivonescimab cohorts across pheochromocytoma/paraganglioma, rhabdomyosarcoma, extramammary Paget, perivascular epithelioid cell tumor, sarcomatoid carcinoma, urachal cancer, neuroendocrine, basal-cell carcinoma, penile, adrenocortical carcinoma, germ-cell, non-clear-cell RCC, prostate, urothelial, and other rare tumors.
- Bispecific-on-bispecific combinations — ivonescimab + cadonilimab (the other Akeso bispecific, PD-1 × CTLA-4) in SCLC and HCC, exploring whether layering two bispecifics improves outcomes over either alone.
Recruiting Trials by Indication
Small Cell Lung Cancer (SCLC) — 15 recruiting (largest indication cluster)
Ivonescimab has become a major investigational backbone in SCLC. The Phase 3 consolidation program is the most advanced:
- NCT07010263 — Phase 3 ivonescimab as consolidation in limited-stage SCLC after concurrent chemoradiation in patients who have not progressed. Positions ivonescimab against the durvalumab/ADRIATIC paradigm in LS-SCLC.
- Multiple Phase 2 ivonescimab + cadonilimab combinations in 1L and recurrent SCLC (the Akeso bispecific-on-bispecific strategy).
- Phase 2 combinations with chemotherapy, radiotherapy, and tarlatamab in extensive-stage and limited-stage SCLC.
Non-Small Cell Lung Cancer (NSCLC) — 13 recruiting
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:
- NCT05899608 — Phase 3 ivonescimab for 1L metastatic NSCLC (China).
- NCT06767514 — HARMONi-7, Phase 3 ivonescimab vs pembrolizumab in 1L metastatic NSCLC with high PD-L1. The second 1L monotherapy head-to-head against pembrolizumab after HARMONi-2; featured in the ASCO 2026 wrap-up as the next confirmatory readout in the HARMONi-2 superiority story.
- NCT06928389 — Phase 3 ivonescimab + docetaxel in advanced NSCLC after 1L progression. Addresses the post-IO chemotherapy setting, a major unmet need after frontline pembrolizumab-based therapy.
- NCT07412262 — Phase 2 chidamide (an HDAC inhibitor) + ivonescimab in advanced NSCLC with acquired resistance to immunotherapy and high YAP expression — a biomarker-defined attempt to reverse IO resistance.
- NCT07158489 — Phase 2 gemcitabine + ivonescimab in advanced NSCLC to overcome resistance to immunotherapy — a chemo-partnered strategy for the post-IO-progression population.
- HARMONi-6 (China, 1L squamous NSCLC ivonescimab + chemo vs tislelizumab + chemo) was presented at the ASCO 2026 Plenary Session on May 31.
- Global Phase 3 HARMONi-3 (1L vs pembrolizumab + chemo, Summit-sponsored) remains blinded after the Q2 2026 squamous-cohort interim PFS analysis did not meet the early-significance threshold; IDMC recommended the trial continue.
Hepatocellular Carcinoma (HCC) — 6 recruiting
Approved in China for 1L HCC (+ lenvatinib); active expansion into TACE combinations and earlier-line settings:
- Phase 2/3 ivonescimab + lenvatinib in 1L advanced HCC (per 2025 NMPA approval).
- Phase 2 ivonescimab + TACE + lenvatinib in intermediate-stage HCC.
- Phase 2 ivonescimab + cadonilimab in advanced HCC (bispecific-on-bispecific).
Colorectal Cancer — 7 recruiting
Including a notable head-to-head Phase 3 against bevacizumab + chemo (the current 1L anti-angiogenic standard):
- NCT07228832 — HARMONi-GI3, Phase 3 ivonescimab + FOLFOX vs bevacizumab + FOLFOX in metastatic CRC. If positive, ivonescimab could displace bevacizumab in the 1L mCRC anti-angiogenic backbone.
- NCT06951503 — Phase 3 AK112 + chemotherapy as 1L treatment for metastatic colorectal adenocarcinoma. CRC has historically been a hard tumor type for checkpoint monotherapy outside MSI-high disease; the VEGF arm of the bispecific is the mechanistic rationale.
Triple-Negative Breast Cancer (TNBC) — 7 recruiting
Phase 3 1L combination + perioperative/adjuvant settings:
- NCT06767527 — Phase 3 AK112 or placebo + nab-paclitaxel as 1L treatment for inoperable locally advanced / metastatic TNBC. Moves the PD-1/VEGF bispecific into the same 1L mTNBC backbone setting where datopotamab deruxtecan (Datroway) received FDA approval on May 22, 2026.
Head & Neck Squamous Cell Carcinoma (HNSCC) — 6 recruiting
Including a head-to-head Phase 3 against pembrolizumab (the current 1L IO standard for HNSCC):
- NCT06601335 — Phase 3 AK112 + AK117 (anti-CD47) vs pembrolizumab in 1L recurrent or metastatic (R/M) HNSCC.
- NCT07264075 — ILLUMINE, Phase 3 ivonescimab alone or in combination with ligufalimab vs pembrolizumab in squamous head & neck cancer (SCCHN).
Pancreatic Cancer — 5 recruiting
- NCT06953999 — Phase 3 ivonescimab + chemo with/without AK117 (anti-CD47) in 1L metastatic pancreatic cancer.
Rare-Tumor Basket Access
For rare or histology-orphan cancers without dedicated ivonescimab trials, a multi-tumor basket Phase 2 offers cohort-based access:
- NCT06683846 — Phase 2 ivonescimab in multiple advanced tumors. Listed cohorts include pheochromocytoma/paraganglioma, rhabdomyosarcoma, extramammary Paget disease, renal angiomyolipoma, perivascular epithelioid cell tumor (PEComa), sarcoma, sarcomatoid carcinoma, urachal cancer, neuroendocrine cancer, basal cell carcinoma, penile cancer, adrenocortical carcinoma, germ-cell tumors, non-clear-cell RCC, clear-cell RCC, prostate cancer, urothelial carcinoma, kidney cancer, and other rare tumors.
Other Indications
- Cervical and gynecologic cancers: 4 trials — Phase 2 combinations with chemoradiation and bevacizumab in advanced cervical, ovarian, and endometrial.
- Sarcoma: 5 trials — Phase 2 ivonescimab + anti-angiogenic TKI combinations, including NCT07655570, a Phase 2 pilot in advanced/metastatic cutaneous angiosarcoma (a vascular sarcoma where the anti-VEGF arm of the bispecific is mechanistically rational).
- Gastric/GEJ: 3 trials — Phase 2 combinations with chemotherapy in 1L and post-progression settings.
- Mesothelioma: 2 trials — Phase 2 combinations with chemotherapy.
- Renal cell carcinoma (RCC): 3 trials — Phase 2 combinations in 1L and post-IO settings, plus NCT07226544, neoadjuvant ivonescimab before surgery in high-risk localized clear-cell RCC — a new move into the curative-intent perioperative setting.
- Nasopharyngeal carcinoma: Phase 2 combinations with chemoradiation.
- Bladder/urothelial: Phase 2 combinations.
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.
Per-Trial Detail: Key Recruiting NCTs
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.
NCT06601335 — Phase 3 ivonescimab (AK112) + AK117 vs pembrolizumab in 1L PD-L1–positive recurrent or metastatic HNSCC
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.
Patient-match CTA: Find Head & Neck Cancer Trials
External reference: View NCT06601335 on ClinicalTrials.gov
NCT06767514 — HARMONi-7, Phase 3 ivonescimab vs pembrolizumab in 1L metastatic NSCLC with high PD-L1 (TPS ≥ 50%)
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.
Patient-match CTA: Find NSCLC Trials
External reference: View NCT06767514 on ClinicalTrials.gov
NCT07228832 — HARMONi-GI3, Phase 3 ivonescimab + mFOLFOX6 vs bevacizumab + FOLFOX in 1L metastatic colorectal cancer
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.
Patient-match CTA: Find Colorectal Cancer Trials
External reference: View NCT07228832 on ClinicalTrials.gov
NCT06767527 — Phase 3 ivonescimab + nab-paclitaxel vs placebo + nab-paclitaxel in 1L inoperable LA / metastatic TNBC
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.
Patient-match CTA: Find Breast Cancer (TNBC) Trials
External reference: View NCT06767527 on ClinicalTrials.gov
NCT07010263 — Phase 3 ivonescimab as consolidation in limited-stage SCLC after concurrent chemoradiation
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.
Patient-match CTA: Find SCLC Trials
External reference: View NCT07010263 on ClinicalTrials.gov
Searching for NCT06145308 or NCT06419621? Full disambiguation for these NCT IDs that often appear in ivonescimab / AK112 searches:
- NCT06145308 — a Phase 2 precision-therapy basket study in recurrent/metastatic salivary gland carcinoma (Cancer Hospital, Chinese Academy of Medical Sciences / National Cancer Center of China), with 20 molecular-typing-defined cohorts. Ivonescimab + investigator-choice platinum doublet is Cohort 12; cadonilimab is Cohort 14. The trial is not ivonescimab-specific — eligibility requires recurrent or metastatic salivary gland carcinoma and the molecular subtype assigned to the relevant cohort. See NCT06145308 on ClinicalTrials.gov for cohort allocation rules.
- NCT06419621 — NOT an ivonescimab trial. This is a Phase 3 study of PM8002 (BNT327), a different PD-1/VEGF bispecific antibody developed by Biotheus (acquired by BioNTech in late 2024), in combination with nab-paclitaxel as first-line treatment in inoperable LA / metastatic triple-negative breast cancer. PM8002 and ivonescimab share a mechanism class but are independent molecules from different companies. See the FAQ below ("Is ivonescimab (AK112) the same as PM8002?") for full disambiguation. The ivonescimab 1L mTNBC analogue is NCT06767527 (accordion above).
Patient Selection and Biomarkers
Ivonescimab trials use a mix of standard immunotherapy biomarkers and indication-specific enrichment:
- PD-L1 expression (TPS or CPS) — key for 1L NSCLC trials (HARMONi-2 was PD-L1-positive specifically; other NSCLC studies test PD-L1-negative populations).
- EGFR-mutation status — the China-approved indication is 1L EGFR-TKI-refractory EGFR-mutant NSCLC; the Summit FDA BLA is for 2L+ EGFR-mutant non-squamous NSCLC after TKI progression.
- Histology (squamous vs non-squamous NSCLC) — squamous lung cancer trials monitor bleeding risk closely (a known anti-angiogenic concern); the HARMONi-3 squamous cohort interim PFS miss may reflect heterogeneity here.
- MSI/MMR status in CRC — some colorectal trials are biomarker-stratified.
- Indication-defining markers — HCC requires confirmed diagnosis (typically AFP + imaging); cervical/gynecologic trials may require HPV or specific histology subsets.
Side Effects and Practical Considerations
- Combined immune + anti-angiogenic profile — the side-effect picture combines what you'd expect from PD-1 inhibitors (immune-related events) and VEGF inhibitors (vascular events).
- Immune-related events — hypothyroidism, skin rash and pruritus, fatigue, immune-mediated colitis, hepatitis, and pneumonitis. Pre-existing autoimmune disease requires careful pre-treatment evaluation.
- Anti-angiogenic events — hypertension (the most common Grade 3+ event reported in trials), proteinuria, bleeding (typically minor; serious hemorrhage and pulmonary embolism are rare but require monitoring). Squamous histologies have historically had higher bleeding risk with anti-angiogenics, and ivonescimab trials in squamous NSCLC monitor for this.
- Delayed wound healing — standard with anti-angiogenic therapies. Plan for treatment interruptions around surgery.
- Combination-specific toxicities — chemotherapy combinations add myelosuppression and neuropathy; lenvatinib combinations add hand-foot syndrome and hypertension on top of ivonescimab's baseline hypertension risk.
- Geographic context — most clinical experience to date is from Chinese trials (which approved ivonescimab); the limited non-Chinese data from Summit's global trials has been broadly consistent.
Frequently Asked Questions
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 September 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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