Cadonilimab (AK104) Clinical Trials (May 2026): 88 Recruiting Interventional Studies

Last updated: May 22, 2026

About Cadonilimab

Active Research Directions in 2026

• Pivotal Phase 3 expansions — 10 ongoing Phase 3 studies span gastric/GEJ adenocarcinoma (perioperative + second-line), cervical cancer (locally advanced), hepatocellular carcinoma (adjuvant + TACE combination), NSCLC (unresectable locally advanced), nasopharyngeal carcinoma, and colorectal cancer (chemo + bevacizumab + MSI-H neoadjuvant)
• Combination with anti-angiogenics — lenvatinib in HCC, bevacizumab in colorectal and HCC, fruquintinib in colorectal, anlotinib in cervical and sarcoma. The IO + anti-angiogenic backbone is the most common architecture across the pipeline
• Chemo-immunotherapy first-line — cadonilimab + platinum/taxane backbones in 1L gastric, esophageal, NSCLC, SCLC, pancreatic, and triple-negative breast cancer
• Radiation combinations — concurrent chemoradiation + cadonilimab in cervical, esophageal, and rectal cancers; SBRT consolidation in oligo-metastatic CRC and NSCLC; intrathecal administration for leptomeningeal disease
• Perioperative / neoadjuvant immunotherapy — multiple Phase 2/3 studies in resectable gastric, esophageal, NSCLC, HCC, and HNSCC asking whether dual checkpoint blockade improves event-free survival
• Bispecific-on-bispecific combinations — cadonilimab (PD-1×CTLA-4) plus ivonescimab (PD-1×VEGF, also Akeso) in SCLC, NSCLC, and HCC, exploring whether layering two bispecifics improves response over either alone

Recruiting Trials by Indication

Gastric / Gastroesophageal Junction Adenocarcinoma (13 recruiting)

Approved 1L indication in China. Active Phase 3 expansions in perioperative and second-line settings, plus HER2-expressing combinations:

• NCT07023315 — Phase 3 cadonilimab + SOX (S-1/oxaliplatin) as perioperative therapy in resectable gastric/GEJ adenocarcinoma.
• NCT06949033 — Phase 3 neoadjuvant cadonilimab + perioperative oxaliplatin in gastric/GEJ.
• NCT06341335 — Phase 3 AK104/placebo + AK109 (anti-VEGFR-2)/placebo + paclitaxel in previously-treated gastric/GEJ.
• NCT06650332 — Phase 1/2 cadonilimab combination in 1L HER2-positive GEJ.

Cervical Cancer (13 recruiting)

First-approved indication (NMPA 2022 for r/m post-platinum monotherapy; later expanded to 1L + chemo ± bevacizumab). Current pipeline focuses on locally advanced disease and concurrent chemoradiation:

• NCT07400536 — Phase 3 in locally advanced cervical carcinoma (LACC), cadonilimab combination.
• NCT05687851 — Phase 2 cadonilimab combined with radiotherapy in LACC.
• NCT06251388 — Phase 2 concurrent chemoradiotherapy followed by cadonilimab maintenance.
• NCT05817214 — Phase 2 cadonilimab + anlotinib for recurrent/metastatic/persistent cervical cancer.

Hepatocellular Carcinoma (HCC) (12 recruiting)

A major Phase 3 focus, with two distinct strategies — adjuvant high-risk-recurrence and intermediate-stage TACE potentiation:

• NCT05489289 — Phase 3 cadonilimab as adjuvant therapy in HCC with high recurrence risk after curative resection.
• NCT06371157 — Phase 3 cadonilimab + lenvatinib + transarterial chemoembolization (TACE) in intermediate-stage HCC.
• NCT06280105 — Phase 2 cadonilimab + regorafenib in HCC.
• NCT06530251 — Phase 1/2 ivonescimab (AK112) in advanced HCC (companion Akeso bispecific).

Colorectal Cancer (12 recruiting)

Active development in both MSS (combined with anti-angiogenics + SBRT) and MSI-H (neoadjuvant resectable) populations:

• NCT06566755 — Phase 3 cadonilimab + chemotherapy + bevacizumab in advanced CRC.
• NCT07412613 — Phase 3 neoadjuvant/adjuvant cadonilimab in resectable MSI-H/dMMR colon cancer.
• NCT05426005 — Phase 1/2 cadonilimab in PD-1/PD-L1-refractory MSI-H/dMMR advanced CRC.
• NCT06551207 — cadonilimab + fruquintinib + SBRT as third-line metastatic CRC.

Non-Small-Cell Lung Cancer (NSCLC) (11 recruiting)

Phase 3 pivotal in unresectable locally advanced disease (consolidation after chemoradiation), plus 1L PD-L1-low and perioperative strategies:

• NCT06617416 — Phase 3 cadonilimab in unresectable locally advanced NSCLC.
• NCT06424821 — Phase 2 cadonilimab + chemotherapy in 1L PD-L1-negative NSCLC.
• NCT06532591 — Phase 2 neoadjuvant/adjuvant cadonilimab + chemotherapy in resectable NSCLC.
• NCT05377658 — Phase 2 AK104 + chemotherapy as neoadjuvant and adjuvant therapy.

Small-Cell Lung Cancer (SCLC) (10 recruiting)

Bispecific-on-bispecific combinations (cadonilimab + ivonescimab) are a distinctive Akeso strategy in SCLC, alongside chemo-IO 1L:

• NCT07245446 — Phase 2 ivonescimab + cadonilimab in 1L extensive-stage SCLC.
• NCT06769971 — Phase 2 ivonescimab + cadonilimab in SCLC.

Esophageal Cancer (15 recruiting)

The largest indication cluster by trial count. Active across locally advanced concurrent chemoradiation, perioperative, and metastatic chemo-IO 1L:

• NCT06356688 — Phase 2 paclitaxel polymeric micelles + cadonilimab in locally advanced ESCC.
• NCT07263919 — Phase 2 perioperative cadonilimab + neoadjuvant chemotherapy in resectable thoracic ESCC.
• NCT06187597 — Phase 2 consolidation after chemoradiation in elderly LA-ESCC.

Nasopharyngeal Carcinoma (NPC)

A Chinese-prevalent disease where Akeso has invested heavily; Phase 3 in locally advanced NPC:

• NCT05941741 — Phase 3 induction chemotherapy + low-dose radiation + cadonilimab in locally advanced NPC.
• NCT06241599 — Phase 2/3 in recurrent or metastatic NPC.

Other Indications

• Cholangiocarcinoma: Phase 2 chemo combinations (NCT05978609, NCT06438822).
• Pancreatic cancer: Phase 2 chemo-IO 1L (NCT05859750), AG + cadonilimab + short-course radiotherapy in LAPC (NCT06472037).
• Soft tissue sarcoma: Phase 2 cadonilimab + anlotinib (NCT05926700); cadonilimab + adriamycin in advanced STS (NCT06367075).
• Breast cancer (TNBC): Phase 2 cadonilimab + chemotherapy 1L/2L (NCT06367088); SBRT + chemo + AK104 neoadjuvant TNBC (NCT06401005).
• Head and neck SCC: Phase 2 neoadjuvant immunotherapy (NCT06444009); AK104 + low-dose radiation in r/m HNSCC after prior IO (NCT06494995).
• Mesothelioma: Phase 2 cadonilimab + bevacizumab + standard chemotherapy (NCT05930665).
• Gynecologic (endometrial, ovarian, vulvar): Phase 1/2 KD01 in gynecologic malignancies (NCT06552598), cadonilimab + chemoradiation in recurrent endometrial (NCT06532539), AK104 in r/m vulvar (NCT05932212).
• Salivary gland carcinoma: Phase 2 precision-therapy combination (NCT06145308).
• Leptomeningeal metastasis: Phase 1/2 intrathecal PD-1/CTLA-4 dual blockade (NCT06762080).

Showing pivotal Phase 3 trials plus selected Phase 2 trials across major indications. The full set of 88 recruiting interventional studies includes additional investigator-initiated combinations not listed above. View the latest on ClinicalTrials.gov.

Patient Selection and Biomarkers

Cadonilimab trials do not converge on a single biomarker the way RET inhibitors or HER2-ADCs do — checkpoint blockade benefits are biology-broad. The most commonly used enrichment or stratification markers in the cadonilimab pipeline are:

• PD-L1 expression (CPS or TPS) — some trials enrich for PD-L1-positive disease; others (notably 1L NSCLC chemo combinations) deliberately target PD-L1-negative populations where single-agent PD-1 inhibitors underperform.
• MSI-H / dMMR status — used in the resectable-CRC neoadjuvant Phase 3 (NCT07412613) and the PD-1-refractory MSI-H CRC Phase 1/2 (NCT05426005).
• HER2 status — HER2-positive gastric/GEJ is its own combination subset (cadonilimab + HER2-directed therapy).
• EBV-associated cancers — the NPC and a subset of gastric trials enrich for or are conducted predominantly in EBV-driven disease.
• Prior IO exposure — multiple trials specifically enroll patients who progressed on prior PD-1/PD-L1 monotherapy, testing whether adding CTLA-4 blockade can recover responses.

Side Effects and Practical Considerations

• Immune-related adverse events — the most common category. Hypothyroidism, skin rash and pruritus, fatigue, immune-mediated colitis, hepatitis, pneumonitis, and (rare) immune-mediated endocrinopathies including adrenal insufficiency and hypophysitis. Pre-existing autoimmune disease requires careful pre-treatment evaluation.
• Compared to ipilimumab + nivolumab — published cadonilimab safety data have generally shown lower Grade 3+ irAE rates than the ipi/nivo combination at active doses, consistent with the tumor-microenvironment-enhanced binding design. The trade-off in efficacy versus the ipi/nivo regimen has not been tested head-to-head.
• Combination-specific toxicities — chemo combinations add myelosuppression and neuropathy; lenvatinib and other TKI partners add hypertension, proteinuria, fatigue, hand-foot syndrome; bevacizumab adds bleeding/hypertension/proteinuria risk.
• Infusion reactions — standard for biologics; pre-medication is used in some protocols.
• Geographic note — most clinical experience to date is from Chinese trials. Pharmacokinetics and safety profile have been broadly consistent across the (more limited) non-Chinese cohorts reported so far.

Frequently Asked Questions