Yidafan (ivonescimab) / Akesobio, Summit Therapeutics - LARVOL DELTA

Ivonescimab vs Placebo Plus Chemo, Phase 3 in Patients with EGFR+ NSCLC Progressed with 3rd gen EGFR-TKI Treatment: HARMONi (IASLC-WCLC 2025) - "Methods : Patients were randomized 1:1 to receive ivonescimab (20 mg/kg) or placebo plus pemetrexed (500 mg/m 2 ) and carboplatin (AUC 5) every 3 weeks for 4 cycles, followed by maintenance pemetrexed plus ivonescimab or pemetrexed plus placebo every 3 weeks with stratification for presence of brain metastases (BM) by region. Ivonescimab plus chemotherapy had a clinically meaningful, statistically significant PFS benefit in patients with EGFR+ NSCLC post-3rd generation EGFR-TKI therapy while maintaining a manageable and favorable safety profile. Efficacy was seen in patients with and without BM and across regions and strengthened by a meaningful, positive OS trend."

Clinical • IO biomarker • P3 data • Hypertension • Lung Cancer • Non Small Cell Lung Cancer • Renal Disease • Solid Tumor • PD-1

Phase III study of ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced squamous non-small cell lung cancer (HARMONi-6) (ESMO 2025) - P3 | "Background Ivonescimab significantly improved PFS over pembrolizumab as first-line therapy for advanced NSCLC in PD-L1 TPS ≥1%...Methods Eligible patients with untreated stage IIIB-IV squamous NSCLC were randomized (1:1) to ivonescimab 20 mg/kg Q3W or tislelizumab 200 mg Q3W, plus paclitaxel (175 mg/m2) and carboplatin (AUC 5) for 4 cycles, followed by ivonescimab or tislelizumab monotherapy as maintenance treatment...Safety analyses revealed treatment-related SAE in 32.3% vs. 30.2%, and grade≥3 hemorrhagic events occurred in 1.9% vs. 0.8%, for ivonescimab and tislelizumab groups, respectively. Conclusions This phase III trial result suggests first-line ivonescimab-chemotherapy may be a new standard of care for advanced/metastatic squamous NSCLC."

Clinical • IO biomarker • IO biomarker • Late-breaking abstract • Metastases • P3 data • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (HARMONi-6): a randomised, double-blind, phase 3 trial. (PubMed, Lancet) - P3 | "In patients with untreated advanced squamous NSCLC, ivonescimab plus chemotherapy showed significantly improved progression-free survival compared with tislelizumab plus chemotherapy, regardless of PD-L1 status, as well as a manageable safety profile. This regimen could be used as a novel first-line treatment in this patient group."

Journal • P3 data • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Phase II trial of neoadjuvant short-course radiotherapy followed by ivonescimab with or without chemotherapy in locally advanced rectal cancer (TRIUNITE-03). (ASCO-GI 2026) - P2 | "The recent REGINA trial demonstrated promising efficacy using a chemotherapy-free regimen comprising short-course radiotherapy (SCRT) combined with nivolumab and regorafenib, reporting notable pathological complete response (pCR) and major pathological response (MPR) rates in pMMR/MSS LARC patients...Patients are randomized 1:1 to two arms: Arm A receives SCRT (25 Gy in 5 fractions) followed, after a 7-day interval, by two cycles of ivonescimab (20 mg/kg IV Q3W) plus CapeOX chemotherapy (oxaliplatin 130 mg/m² IV on day 1; capecitabine 850-1000 mg/m² orally twice daily on days 1-14)...Accrual began in February 2025 across multiple centers in China. Clinical trial information: NCT06718543."

Clinical • IO biomarker • Metastases • P2 data • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Rectal Adenocarcinoma • Rectal Cancer • Solid Tumor

Phase II trial of ivonescimab in patients with advanced clear cell renal cell carcinoma previously treated with immune checkpoint blockade: IVORY Trial (NCT06940518) (KCRS 2025) - P2 | "In treatment-naïve non-small cell lung cancer, ivonescimab has recently shown superior clinical activity over pembrolizumab (HARMONi-2 Xiong et al. Potential clinical activity signals and translational insights obtained will (1) shape the understanding of approaches to revert ICI-resistance and (2) open venues for further clinical testing of this agent in mccRCC. NCT: NCT0694051."

Checkpoint block • Checkpoint inhibition • Clinical • Metastases • P2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

A phase II study of AK112 (PD-1/VEGF bispecific) in combination with chemotherapy in patients with advanced non-small cell lung cancer. (ASCO 2022) - P2 | "Background: Based on IMPOWER 150, atezolizumab in combination with bevacizumab and platinum-based chemotherapy has been the first-line treatment for advanced non-squamous NSCLC with negative driver genes...Enrolled pts were divided into three cohorts: Previously untreated advanced NSCLC pts with wide-type EGFR/ALK (Cohort 1), pts with EGFR mutations who had failed prior EGFR-TKI therapies without T790M mutation or failed osimertinib treatment (Cohort 2), and pts who progressed after anti-PD-1/L1 and platinum-based chemotherapy (Cohort 3). Pts were treated with 10mg/kg or 20mg/kg AK112 once every 3 weeks in combination with carboplatin and pemetrexed or carboplatin and paclitaxel for Cohort 1/2, and docetaxel for Cohort 3... AK112 plus chemotherapy has shown a promising anti-tumor efficacy in each cohort and warrants potentially superior safety in comparison to anti-PD-(L)1 and anti-VEGF combination therapies in advanced NSCLC. PFS and ORR were also significantly..."

Clinical • Combination therapy • IO biomarker • P2 data • Anemia • Hematological Disorders • Leukopenia • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Thrombocytopenia • ALK • EGFR

Ivonescimab versus pembrolizumab for PD-L1-positive non-small cell lung cancer (HARMONi-2): a randomised, double-blind, phase 3 study in China. (PubMed, Lancet) - P3 | "Ivonescimab significantly improved PFS compared with pembrolizumab in previously untreated patients with advanced PD-L1 positive non-small cell lung cancer. Therefore, ivonescimab might represent another treatment option in the first-line setting for PD-L1-positive advanced non-small cell lung cancer."

Clinical • IO biomarker • Journal • P3 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • ALK • EGFR • PD-L1

Health-related quality of life with ivonescimab versus pembrolizumab for PD-L1 positive, non-small cell lung cancer (HARMONi-2): a randomised, double-blind, phase 3 study in China (ELCC 2026) - No abstract available

Clinical • HEOR • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Treatment for Advanced Non-small Cell Lung Cancer With Actionable Genomic Alterations After Targeted Treatment and Chemotherapy (An Expanded Lung-MAP Treatment Trial) (clinicaltrials.gov) - P2 | N=117 | Not yet recruiting | Sponsor: SWOG Cancer Research Network

IO biomarker • New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • HER-2 • NTRK • PD-L1 • RET • ROS1

Final overall survival analysis of HARMONi-A study comparing ivonescimab plus chemotherapy to chemotherapy alone in patients with EGFR+ NSCLC progressed on EGFR-TKI treatment (SITC 2025) - P3 | "Here, we report the overall survival (OS) results in the final and only formal OS analysis of this study.Methods Patients (pts) were randomized 1:1 to receive ivonescimab (20 mg/kg) or placebo plus pemetrexed (500 mg/m2) and carboplatin (AUC 5) every 3 weeks for 4 cycles, with presence of brain metastases (BM) and prior exposure to 3rd generation EGFR-TKI as two stratification factors. The safety of the combination therapy remained favorable, with no new safety signals identified.Conclusions Ivonescimab plus chemotherapy demonstrated a clinically meaningful and statistically significant OS benefit in pts with EGFR+ NSCLC post EGFR-TKI therapy in this randomized Phase 3 HARMONi-A study. This study results establish ivonescimab plus chemotherapy as a new standard of care for EGFR+ NSCLC patients who progressed on EGFR-TKI treatments.Trial Registration This study has been registered on ClinicalTrial.gov under the registration number NCT05184712."

Clinical • Late-breaking abstract • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-1

Efficacy and safety of ivonescimab in non-small cell lung cancer: a systematic review and meta-analysis of emerging clinical data (Front Pharmacol) - "5 studies comprising 1,365 patients were included. AK112-based regimens significantly improved ORR (OR = 1.65, 95% CI: 1.31–2.09) and DCR (OR = 2.29, 95% CI: 1.18–4.44) compared to control treatments. A significant progression in PFS was observed (HR = 0.53, 95% CI: 0.45–0.62). The PFS benefit was consistent across all PD-L1 expression subgroups."

Retrospective data • Non Small Cell Lung Cancer

ctDNA-guided Treatment Decision-making (clinicaltrials.gov) - P2 | N=122 | Recruiting | Sponsor: Fudan University

Circulating tumor DNA • New P2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • HER-2

Ivonescimab Plus Chemotherapy in Non-Small Cell Lung Cancer With EGFR Variant: A Randomized Clinical Trial. (PubMed, JAMA) - P3 | "Participants received ivonescimab (n = 161) or placebo (n = 161) plus pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy of ivonescimab plus pemetrexed or placebo plus pemetrexed. Ivonescimab plus chemotherapy significantly improved progression-free survival with tolerable safety profile in TKI-treated non-small cell lung cancer. ClinicalTrials.gov Identifier: NCT05184712."

Clinical • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

A Single-Arm, Multicenter Clinical Study of Eribulin Mesylate in Combination with Ivonescimab as First-Line Treatment for Unresectable Locally Advanced or Metastatic Triple-Negative Breast Cancer (ChiCTR) - P2 | N=50 | Not yet recruiting | Sponsor: Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University; Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University

New P2 trial • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PGR

A Phase II Clinical Study of Neoadjuvant Immunogenic Radiotherapy Followed by Ivonescimab (PD-1/VEGF-A Bispecific Antibody) And Chemotherapy In Stage II-III Non-small Cell Lung Cancer (ELCC 2026) - No abstract available

Clinical • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Intracranial (IC) Efficacy of Ivonescimab (Ivo) Plus Chemotherapy (Chemo) in Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI)–Resistant, EGFR-Mutated Non-Small Cell Lung Cancer (NSCLC) in the HARMONi Study (ELCC 2026) - No abstract available

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Health-Related Quality of Life in Patients Previously Treated with an EGFR-TKI from HARMONi: A Phase 3 Trial of Ivonescimab vs Placebo Plus Chemotherapy (ELCC 2026) - No abstract available

Clinical • HEOR • P3 data • Lung Cancer

Akeso Receives Fifth Breakthrough Therapy Designation from NMPA for Ivonescimab in First-Line Treatment of Advanced Biliary Tract Cancer (PRNewswire) - "A randomized, controlled, multicenter, registrational Phase III clinical study (AK112-309/HARMONi-GI1) is evaluating ivonescimab plus chemotherapy versus durvalumab (a PD-L1 inhibitor) plus chemotherapy for first-line treatment of advanced BTC....Encouraging results from a Phase 1b/II study, presented at the 2024 American Society of Clinical Oncology (ASCO) Annual meeting, support the potential of the ivonescimab combination therapy as a superior first-line treatment for advanced BTC."

Breakthrough therapy • Biliary Tract Cancer

A Phase II Clinical Trial of Anti-EGFR Antibody-drug Conjugate (ADC) Combined With or Without Immune Checkpoint Inhibitors in the Neoadjuvant Treatment of Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: West China Hospital

Checkpoint inhibition • New P2 trial • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Ivonescimab in metastatic clear cell renal cell carcinoma (mccRCC) after immune checkpoint inhibitor therapy: The phase II IVORY trial. (ASCO-GU 2026) - P2 | "Clinical Trial Registry Number: NCT06940518. The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

Checkpoint inhibition • Metastases • P2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

Ivonescimab combined with chemotherapy treated with recurrent/persistent ovarian, fallopian tube, or primary peritoneal clear cell carcinoma patients：a single arm, open-label , single center exploratory study (ChiCTR) - P=N/A | N=20 | Not yet recruiting | Sponsor: West China Second Hospital of Sichuan University; West China Second Hospital of Sichuan University

New trial • Platinum resistant • Platinum sensitive • Clear Cell Carcinoma • Oncology • Ovarian Cancer

Prospective, Single-Center, Single-Arm Clinical Study of Ivosidenib (AK112) Combined with Chemotherapy for Neoadjuvant Treatment of Locally Advanced Oral Squamous Cell Carcinoma (ChiCTR) - P4 | N=15 | Not yet recruiting | Sponsor: The first affiliated hostipal of nanchang university; The first affiliated hostipal of nanchang university

New P4 trial • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Huaxi: Perioperative Ivonescimab Plus S-1 and Oxaliplatin (SOX) for Locally Advanced Gastric or GEJ Adenocarcinoma (clinicaltrials.gov) - P2 | N=154 | Not yet recruiting | Sponsor: Sichuan University

New P2 trial • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

The Safety and Efficacy of AK112 Combined Chemotherapy and Brain Radiotherapy in EGFR TKIs Resistant NSCLC with Brain Metastases: a single-arm phase 1b-2 trial (ChiCTR) - P1/2 | N=31 | Recruiting | Sponsor: Sichuan Cancer Hospital; Sichuan Cancer Hospital

New P1/2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of Ivonescimab Plus Neoadjuvant Chemotherapy Followed by Chemoradiotherapy for High-Risk Locally Advanced Cervical Cancer (ChiCTR) - P2 | N=42 | Not yet recruiting | Sponsor: Women’s Hospital, Zhejiang University School of Medicine; Women’s Hospital, Zhejiang University School of Medicine

New P2 trial • Cervical Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • PD-L1