62 Ivonescimab (AK112) Clinical Trials Recruiting Now (June 2026): NSCLC, SCLC, HCC, Colorectal, TNBC — PD-1/VEGF Bispecific (HARMONi-7, HARMONi-GI3, ILLUMINE)

Last updated: June 9, 2026

About Ivonescimab

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) — 11 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.
• 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: 4 trials — Phase 2 ivonescimab + anti-angiogenic TKI combinations.
• 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): 2 trials — Phase 2 combinations in 1L and post-IO settings.
• 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.

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