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

A Study of AK130 in Combination With AK112 for the Treatment of Advanced Biliary Tract Cancer (clinicaltrials.gov) - P1/2 | N=135 | Not yet recruiting | Sponsor: Akeso

New P1/2 trial • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor

HARMONi-6: AK112 in Combination With Chemotherapy in Advanced Squamous Non-Small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=532 | Active, not recruiting | Sponsor: Akeso | Recruiting ➔ Active, not recruiting | N=396 ➔ 532 | Trial completion date: Dec 2025 ➔ Dec 2026

Enrollment change • Enrollment closed • IO biomarker • Trial completion date • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Cadonilimab in combination with ivonescimab and chemotherapy as first-line (1L) therapy in patients with advanced gastric (G) or gastroesophageal junction adenocarcinoma (GEJA). (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT06196697 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Combination therapy • Metastases • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

Ivonescimab in Combination with Chemotherapy Demonstrates Statistically Significant and Strongly Positive Results in First-Line Treatment of Squamous Non-Small Cell Lung Cancer (sq-NSCLC) vs. Tislelizumab in Combination with Chemotherapy (PRNewswire) - P3 | N=396 | HARMONi-6 (NCT05840016) | Sponsor: Akeso | "The Independent Data Monitoring Committee (IDMC) declared that the study had met its primary endpoint of progression-free survival (PFS) at the first pre-specified interim analysis....Data from the HARMONi-6 study show that, in the intention-to-treat (ITT) population, ivonescimab plus chemotherapy decisively beat tislelizumab plus chemotherapy in terms of progression-free survival (PFS). The ivonescimab combination showed clinically meaningful PFS benefits in both PD-L1-positive and PD-L1-negative populations. The trial enrolled a total of 532 patients, approximately 63% of whom had centrally located squamous cell carcinoma, a distribution consistent with real-world patient populations. Ivonescimab demonstrated a favorable safety profile, with no new safety signals identified....Detailed results from the HARMONi-6 study will be presented at an upcoming medical conference later this year."

DSMB • P3 data • Non Small Cell Lung Cancer

HX016-9, a novel PD1xVEGF BsAb, as a new candidate treatment of solid tumors (AACR 2025) - "With the clinical confirmation of the superior efficacy of AK112, a first-in-class (FIC) PD1xVEGF bispecific antibody (BsAb), in the treatment of NSLCL cancers, over the PD1 monoclonal antibody (mAb), as shown in a head-to-head phase III trial, we set out to engineer a novel and potentially best-in-class (BIC) PD1xVEGF BsAb using a unique PD1 (HX008, an approved PD1-mAb) and a novel VEGF (HX006, a mAb with more favor activity over Avastin) mAb sequences. In a xenograft A549 NSCLC tumor in immunocompromised mice, HX016-9 also caused anti-tumor activity that can be attributed to anti-VEGF function. These activities are comparable or superior to those of the FIC molecule, warranting the HX016-9 candidacy to move into IND-enabling evaluation and further clinical development."

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

DIVON: Disitamab Vedotin Combined With Ivonescimab in Cisplatin-Ineligible Muscle-Invasive Bladder Cancer (clinicaltrials.gov) - P1/2 | N=30 | Not yet recruiting | Sponsor: Sun Yat-sen University

New P1/2 trial • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • PD-L1

A Phase II Study on Ivonescimab Plus AG Regimen as Neoadjuvant Therapy for Borderline Resectable Pancreatic Cancer (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Tianjin Medical University Cancer Institute and Hospital

New P2 trial • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

A Phase III, Randomized, Controlled and Multi-center Study of AK112 and Chemotherapy in First-line Metastatic Colorectal Cancer (clinicaltrials.gov) - P3 | N=560 | Not yet recruiting | Sponsor: Akeso

New P3 trial • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor

A randomized phase 3 study of ivonescimab plus chemotherapy versus pembrolizumab plus chemotherapy for the first-line treatment of metastatic non–small cell lung cancer: HARMONi-3. (ASCO 2025) - P3 | "Clinical Trial Registration Number: NCT05899608 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Metastases • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

CT111, a novel trispecific PD-1 x CTLA-4 x VEGF single-domain antibody, synergistically targets exhausted T cells and promotes cooperative antitumor effects (AACR 2025) - "CT111 is a novel, potential first-in-class single-domain trispecific antibody that can simultaneously target PD-1 and CTLA-4 immune checkpoints on exhausted T cells, while also targeting VEGF-mediated tumor angiogenesis to overcome immune suppression synergistically within solid tumors."

Trispecific • Oncology • Solid Tumor • CTLA4 • IFNG

Summit Therapeutics Reports Financial Results and Operational Progress for the First Quarter Ended March 31, 2025 (Businesswire) - "We expect to disclose topline results from HARMONi in mid-2025. Enrollment continues in HARMONi-3 and the initial patients have been enrolled in the US in HARMONi-7."

Enrollment status • P3 data: top line • Non Small Cell Lung Cancer

Dual targeting of VEGF and PD-1: A phase I/II trial of ivonescimab, a novel bispecific antibody, in recurrent glioblastoma. (ASCO 2025) - P1/2 | "Clinical Trial Registration Number: NCT06672575 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

P1/2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • PD-1

Ivonescimab Receives NMPA Approval for First-Line Treatment of PD-L1-Positive NSCLC, Based on Breakthrough Head to Head Phase III Trial Demonstrating Superior Efficacy Over Pembrolizumab (PRNewswire) - "Akeso, Inc...has received approval from the National Medical Products Administration (NMPA) for its supplementary New Drug Application (sNDA) for use as a monotherapy for the first-line treatment of PD-L1-positive (TPS ≥ 1%) non-small cell lung cancer (NSCLC) in patients who are negative for epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK) gene mutations. This indication marks Ivonescimab's second major approval....The sNDA approval is based on the breakthrough results of the AK112-303/HARMONi-2 Phase III study, which is a randomized, double-blind, controlled study that directly compared ivonescimab with pembrolizumab in first line PD-L1 positive NSCLC."

China approval • Evidence highlight • Non Small Cell Lung Cancer • PD-L1

Phase II Trial of Ivonescimab in Previously Treated Patients With Advanced Clear Cell Renal Cell Carcinoma (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P2 trial • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Ivonescimab (PD-1/VEGF bispecific antibody) combined with HAIC for first-line treatment of unresectable hepatocellular carcinoma (uHCC): A prospective, single-arm phase II study. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT06375486 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • P2 data • Hepatocellular Cancer • Oncology • Solid Tumor • PD-1

Phase 2 study of Ivonescimab in patients with cutaneous squamous cell carcinoma (AACR 2025) - P2 | "Active recruitment and enrollment are ongoing at The University of Texas MD Anderson Cancer Center, Houston, Texas. ClinicalTrials.gov (NCT06567314)"

Clinical • IO biomarker • P2 data • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

Summit stock crashes as Akeso shares bispecific's first overall survival data in Keytruda head-to-head trial (Fierce Pharma) - "Akeso has shared for the first time overall survival data from a high-profile Keytruda head-to-head trial for its PD-1xVEGF bispecific ivonescimab-and investors in the company's partner Summit Therapeutics aren’t taking the result too well. Summit’s stock price on the Nasdaq plummeted by nearly 37% following Akeso’s revelation before a trading halt was initiated. In announcing (Chinese) ivonescimab’s Chinese approval in first-line PD-L1-positive non-small cell lung cancer on Friday, Akeso noted that the bispecific drug slashed the risk of death by 22.3% versus Keytruda at an interim analysis of the closely watched HARMONi-2 trial. The number apparently didn’t cross the statistical significance bar, which had an alpha assignment of 0.0001. The analysis was performed when 39% of prespecified deaths for the final analysis were recorded."

P3 data • Stock price • Non Small Cell Lung Cancer

Unveiling the Synergistic Potential: Bispecific Antibodies in Conjunction with Chemotherapy for Advanced Non-Small-Cell Lung Cancer Treatment. (PubMed, Curr Oncol) - "Recent clinical trials have shown improved progression-free survival and overall survival when bsAbs such as amivantamab are combined with chemotherapy, underscoring their potential to transform NSCLC treatment. Many other clinical trials are underway that are evaluating newer bsAbs, such as ivonescimab, which targets PD1 and VEGF. This review also discusses ongoing clinical trials investigating various bsAbs targeting EGFR, PD-1, PD-L1, HER2, and other pathways, highlighting the future directions of bsAb-based therapies. As the field evolves, bsAbs are poised to become a cornerstone of multimodal NSCLC treatment, offering more effective and personalized therapeutic options for patients with advanced disease."

IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2

Phase II Study of Anti-PD-1/VEGF Bispecific Antibody Ivonescimab in Patients With Previously Treated Metastatic Colorectal Cancer (clinicaltrials.gov) - P2 | N=90 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P2 trial • Colorectal Cancer • Oncology • Solid Tumor

ctDNA-MRD Guided Escalation of Ivonescimab and Docetaxel in Advanced NSCLC With Long-Term Responses to First-line Immunotherapy (CR1STAL-Adaptive) (clinicaltrials.gov) - P2 | N=70 | Not yet recruiting | Sponsor: Second Xiangya Hospital of Central South University

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

The evolving immuno-angiogenic paradigm in NSCLC: lessons from ivonescimab. (PubMed, Nat Rev Clin Oncol) - No abstract available

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

A Prospective, Single Arm, Open Label, Phase II Clinical Study on the Efficacy and Safety of Ivonescimab (AK112) Combined With TAS-102 in the Treatment of Refractory MSS/pMMR Advanced Colorectal Cancer (clinicaltrials.gov) - P=N/A | N=35 | Enrolling by invitation | Sponsor: Huai'an First People's Hospital

New trial • pMMR • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor

MIRACLE3: Phase II study of Ivonescimab plus radiotherapy and chemotherapy as first-line treatment in MSS colorectal cancer patients with unresectable liver/lung metastases — Trial in progress (ESMO-GI 2025) - No abstract available

Clinical • P2 data • Colorectal Cancer • Oncology • Solid Tumor

IDP-002 is a PD-1xCD6 bispecific antibody that enables complete PD-1 receptor occupancy and enhances cytotoxic over regulatory T cell responses (AACR 2025) - "Importantly, the recently demonstrated superiority of the PD-1xVEGF bispecific antibody (bsAb) ivonescimab over pembrolizumab in PD-L1+ advanced NSCLC suggests greater PD-1 receptor occupancy (achieved through high-avidity PD-1 binding of ivonescimab/VEGF multivalent complexes) leads to significantly deeper clinical responses.Enhanced PD-1 receptor occupancy may also be achieved with cis-acting bsAbs that target PD-1 and an abundant T cell surface protein, enabling more efficient PD-1 blockade compared to that achieved with conventional mAbs. Enhanced effector T cell responses observed with IDP-002 derive from a combination of complete PD-1 blockade and the engagement of unique signaling pathways downstream of CD6. IDP-002 has the potential to become a leading therapeutic option for the next generation of PD-1 antagonists."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • FOXP3 • PD-L1

...Head to Head Phase III Trial Demonstrating Superior Efficacy Over Pembrolizumab (PRNewswire) - P3 | N=398 | HARMONi-2 (NCT05499390) | Sponsor: Akeso | "Ivonescimab demonstrated a statistically significant improvement in the trial's primary end point, median progression-free survival (PFS) when compared to pembrolizumab, with a median PFS of 11.14 months, achieving a hazard ratio (HR) of 0.51 reducing the risk of disease progression or death by 49%; An interim analysis of OS conducted at 39% data maturity (α=0.0001), indicated a clinically meaningful improvement in OS with ivonescimab compared to pembrolizumab, with a hazard ratio (HR) of 0.777, reflecting a 22.3% reduction in the risk of death; Ivonescimab is the first therapy to achieve statistically significant positive results in a Phase III trial compared with pembrolizumab in a head-to-head setting; Ivonescimab represents a new, more effective, and safer 'chemotherapy-free' option for the first-line treatment of NSCLC."

P3 data • Non Small Cell Lung Cancer