恒星集团(中国)

Note:

The following product information is intended for use by healthcare professionals only. 

The following product may not have been approved and/or licensed for marketing in all countries where this website is accessible. 

The world's first approved bispecific antibody with a "tumor immunotherapy + anti-angiogenesis" mechanism

依达方® (PD-1/VEGF bispecific, Ivonescimab injection)

 

依达方® is the world's first-in-class PD-1/VEGF bispecific immunotherapy drug, independently developed by Akeso. It has received marketing approval from China's National Medical Products Administration (NMPA) for the treatment of EGFR mutated, locally advanced, or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) in patients who have progressed after EGFR-TKI treatment. This approval marks it as the world's first-ever approved PD-1/VEGF bispecific antibody drug with a combined mechanism of tumor immunotherapy and anti-angiogenesis.

 

Ivonescimab is currently being evaluated in several head-to-head studies, both domestically and internationally, across various lung cancer patient subgroups. China's NMPA has accepted a supplemental New Drug Application (sNDA) and granted priority review for ivonescimab as a monotherapy for the first-line treatment of NSCLC patients with positive PD-L1 expression. Ivonescimab is poised to establish a new standard of care as a chemo-free first-line treatment for lung cancer. This sNDA submission is supported by data from the AK112-303/HARMONi-2 study, which previously demonstrated ivonescimab's superior efficacy compared to pembrolizumab as monotherapy in a phase III head-to-head clinical trial, making ivonescimab the only drug achieved this milestone globally. Additionally, a phase III clinical trial is ongoing, comparing ivonescimab plus chemotherapy against tislelizumab plus chemotherapy as a first-line treatment for squamous NSCLC. Further studies sponsored by our partner, Summit, are also underway. These include a global multi-regional phase III study of ivonescimab combined with chemotherapy for the treatment of EGFR-mutant, locally advanced, or metastatic non-squamous NSCLC in patients who have progressed after EGFR-TKI treatment, as well as a global multi-regional phase III clinical trial comparing ivonescimab plus chemotherapy versus pembrolizumab plus chemotherapy as a first-line treatment for squamous NSCLC patients.

 

Ivonescimab has been studied in over 17 indications, both as a monotherapy and in combination therapy, including Lung cancer, head and neck squamous cell carcinoma, biliary tract carcinoma, pancreatic cancer, breast cancer, hepatocellular carcinoma, colorectal cancer and other tumors.

Mechanism of Action (MOA) 

① Dual Functions: Anti-Angiogenesis and Checkpoint Blockade

·

Ivonescimab is engineered by fusing the antigen-binding fragment of an anti-PD-1 monoclonal antibody in a single-chain variable fragment (scFv) format with a full anti-VEGF monoclonal antibody. This creates a novel tetravalent molecule that integrates two well-established oncology mechanisms: anti-angiogenesis and checkpoint blockade.

·

By inhibiting VEGF, ivonescimab enhances the effectiveness of immunotherapy through modulation of the tumor microenvironment.

·

Strengthening the PD-1 blockade contributes to the activation of T cells.

② Synergistic Antitumor Activity: Simultaneous PD-1 and VEGF Blockade with Cooperative Binding

·In a mature tumor microenvironment (TME), VEGF dimer facilitate the interconnection or "daisy chaining" of multiple ivonescimab molecules. This enhances the synergistic effects of VEGF and PD-1 blockade.

·The presence of VEGF amplifies PD-1 binding strength by more than 18-fold.

·The presence of PD-1 enhances VEGF binding strength by over 4-fold. 

③ Safety Benefits: Engineered Fc-Null Region to Optimize Anti-Tumor Activity and Safety

·By introducing two amino acid mutations in the Fc fragment, ivonescimab significantly reduces potential antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC) effects.

·The Fc-null design notably decreases the incidence of cytokine release syndrome (CRS) and effectively minimizes potential immune-related adverse effects.

·Ivonescimab has the potential to selectively accumulate in the tumor microenvironment, where PD-1 and VEGF levels are higher compared to healthy tissue. This targeted approach significantly reduces the incidence of adverse events typically associated with anti-VEGF therapies.

Global New Mechanism

Ivonescimab is the world's first approved bispecific antibody drug that combines tumor immunotherapy with anti-angiogenesis mechanisms. By simultaneously targeting both PD-1 and VEGF, ivonescimab achieves efficient synergy between immunotherapy and anti-angiogenesis within tumor tissues, resulting in enhanced synergistic antitumor activity. Independently developed by Akeso, ivonescimab is unique; no similar products or drugs with this dual mechanism of action had been approved globally before its approval.

Overseas Commercialization

With a total transaction value exceeding $5 billion, plus double-digit royalties on net sales in licensed territories, Akeso granted Summit Therapeutics exclusiverights to develop and commercialize ivonescimab in the U.S., Canada, Europe, Japan, Central and South America, the Middle East, and Africa. This landmark deal set a record at the time for the highest out-licensing transaction value for a single innovative drug from China.

Upgrading the SOC

The Phase III clinical trial evaluated ivonescimab as a monotherapy against pembrolizumab in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (PD-L1 TPS >1%). The trial met its primary endpoint of progression-free survival (PFS) and demonstrated statistically significant superiority, making ivonescimab the only drug globally to show superior efficacy compared with pembrolizumab as monotherapy in a head-to-head phase III clinical trial.

Breakthrough Therapy Designations

Ivonescimab was selected into National Major Scientific and Technological Special Project for "Significant New Drugs Development". Recognized for its exceptional clinical value, it has been granted three Breakthrough Therapy Designations by the NMPA Center for Drug Evaluation (CDE) for the treatment of lung cancer.

Product information stated by NMPA in Approved Drug Catalog of China:

[Name]

Generic Name：Ivonescimab Injection

Brand Name：依达方®

English Name：Ivonescimab Injection

Chinese Pinyin：Yiwoxi Dankang Zhusheye

[Ingredients]

APIs：Ivonescimab.

Excipients：Histidine, histidine hydrochloride, sucrose, polysorbate 80 (II) and water for injection.

[Appearance]

This product is a colorless to pale yellow clear liquid, and may be slightly opalescent.

[Indications]

This product, in combination with pemetrexed and carboplatin, is indicated for the treatment of patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) with EGFR mutations, who have experienced disease progression following treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs).

[Specification]

100 mg（10mL）/bottle

See Directions for Use for [Usage and Dosage], [Adverse Reactions], [Contraindications], [Precautions], etc.

Indications

1L Lung Cancer

2/3L Lung Cancer
& Adj. therapy

Biliary tract Cancer

Ovarian Cancer

Other Tumors

Ivonescimab 1L Treatment for PD-L1 + NSCLC (sNDA )

 Decisively beats pembrolizumab head-to-head(Mono)

  1. when PD-L1 TPS>1%

  2. 60.0%

    ORR

  3. 97.1%

    DCR

  1. when PD-L1 TPS 1%~49%

  2. 50%

    ORR

  3. 95.5%

    DCR

 ·Patients with different PD-L1 expression levels all showed good antitumor efficacy.

Ivonescimab  1L Treatment (+Chemo) for NSCLC

Exhibits equally good antitumor activity for both nsq and sq types

  1.  ·  For Squamous NSCLC：
  2. 71.4%

    ORR

  3. 90.5%

    DCR

  4. 12.7
    months

    mDOR

  5. 11.1
    months

    mPFS

  6. 65.1%

    9-month PFS Rate

  1.  ·  For Non-Squamous NSCLC: 
  2. 54.2%

    ORR

  3. 95.8%

    DCR

  4. 15.4
    months

    mDOR

  5. 13.3
    months

    mPFS

  6. 58.9%

    9-month PFS Rate

  7. 81.9%

    9-month mOS Rate

  8. 90.4%

    9-month OS Rate

Ivonescimab 1L Treatment (+Chemo) for Extensive-Stage SCLC

Superior to PD-L1+ Chemo regimens
  1. 83%

    ORR

  2. 91%

    DCR

  3. not reached

    OS

  4. not reached

    PFS

Lung Cancer is the leading cause of cancer-related mortality globally, with a prevalence ranking second among all malignant tumors. Non-Small Cell Lung Cancer (NSCLC) accounts for approximately 80% to 85% of all lung cancers.

EGFRm NSCLC progressed after EGFR-TKl treatment (Marketed)

Significantly reduces the risk of disease progression or death

 ·

Compared to the Control Group, Ivonescimab combination therapy significantly improves PFS and reduces the risk of disease progression or death by 54%.Median PFS: 7.1 months vs 4.8 months; PFS HR: 0.46 (P < 0.001)

  1. 0.40

    基线脑转移PFS HR

  2. 0.48

    exon 19缺失PFS HR

  3. 0.22

    T790M突变PFS HR

 ·

Compared to the Control Group, the Ivonescimab combination therapy shows a significant trend toward prolonged overall survival (OS), reducing the risk of death by 20%. Median Follow-Up of 17.6 Months: Median OS is 17.1 months vs 14.5 months  HR = 0.8, Sensitivity Analysis HR = 0.77 

 

NSCLC Progressing on PD-1/L1 Monotherapy

Still exhibits good antitumor activity

 ·when Median Follow-Up of 24.7 Months
  1. 40%

    ORR

  2. 80%

    DCR

  3. 12.7
    months

    mDoR

  4. 7.1
    months

    mPFS

  5. 17.1
    months

    mOS

  6. 65%

    12-month OS Rate

Neoadjuvant Treatment for NSCLC

Shows significant clinical potential & broad prospects

 · Mono： Neoadjuvant Treatment for Resectable NSCLC (N=10)  pCR = 30%, MPR = 60%；

 · +Chemo：Neoadjuvant Treatment for Resectable NSCLC pCR = 44%, MPR = 74%

 

Lung Cancer is the leading cause of cancer-related mortality globally, with a prevalence ranking second among all malignant tumors. Non-Small Cell Lung Cancer (NSCLC) accounts for approximately 80% to 85% of all lung cancers.

Ivonescimab Combined with Chemotherapy for 1L BTC Treatment

 

 ·ORR is 63.6% (14/22), with an ORR of 77.8% (7/9) for gallbladder cancer patients and a DCR of 100% (22/22))

 ·Median PFS is 8.5 months (95% CI, 6.8-9.9), 6-month PFS rate is 84.2% (95% CI, 58.7-94.6)

 ·Median OS is 16.8 months (95% CI, 9.8-unassessed), 9-month OS rate is 81.8% (95% CI, 58.5-92.8)

 

 

Cholangiocarcinoma (BTC) is a group of highly heterogeneous malignant tumors originating from the bile ducts and gallbladder, with poor prognosis. 50% of biliary malignancy patients are already at an advanced stage at diagnosis, with a survival period of less than 1 year.

 Ivonescimab for Platinum-Resistant Ovarian Cancer

Shows superior efficacy

  1. 20mg/kg

  2. 33.3%

    ORR

  3. 88.9%

    DCR

  1. 10mg/kg

  2. 16.7%

    ORR

  3. 50.0%

    DCR

Ovarian Cancer is the most lethal gynecological malignancy, with most patients experiencing disease relapse after initial platinum-based chemotherapy. Platinum-Resistant/Refractory Epithelial Ovarian Cancer (PROC) represents a high unmet medical need with limited treatment options, and a median survival of only 12-15 months.

 In addition to focusing on various types of lung cancer, Ivonescimab is also being explored in 17 indications of tumors including pancreatic cancer, breast cancer, hepatocellular carcinoma, and colorectal cancer, with global clinical studies ongoing. 

Academic Publications

JAMA Network

Ivonescimab Plus Chemotherapy in Non–Small Cell Lung Cancer With EGFR Variant - A Randomized Clinical Trial

2024 ASCO

The safety and efficacy of ivonescimab in combination with chemotherapy as first-line treatment for advanced biliary tract cancer

Journal of Thoracic Oncology, Vol 19.

A Phase 1b Study of Ivonescimab, a Programmed Cell Death Protein-1 and Vascular Endothelial Growth Factor Bispecific Antibody, as First- or Second-Line Therapy for Advanced or Metastatic Immunotherapy-Naïve NSCLC

2023 eClinicalMedicine (Part of The Lancet Discovery Science), Vol 62.

AK112, a novel PD-1/VEGF bispecific antibody, in combination with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC): an open-label, multicenter, phase II trial

Recommended Guidelines

Non-Squamous NSCLC with Extensive Progression After EGFR-TKIs Treatment

Class 1 recommendation in the "Chinese Guidelines for the Treatment of Stage IV Primary Lung Cancer (2024 Edition)" for the treatment of extensively progressed non-squamous NSCLC following EGFR-TKI therapy

Non-Squamous NSCLC with Extensive Progression After EGFR-TKIs Treatment

Recommended as a Category 1 option in the "Chinese Guidelines for the Treatment of Stage IV Primary Lung Cancer (2024 Edition)"

Non-Squamous NSCLC with Extensive Progression After EGFR-TKIs Treatment

Included in the "Expert Consensus on Immunotherapy for Advanced Non-Small Cell Lung Cancer with Oncogenic Driver Mutations (2023 Edition)" for the treatment of advanced non-squamous NSCLC that is T790M-negative and resistant to first- or second-generation TKIs, or resistant to third-generation TKIs, and has not undergone platinum-based chemotherapy.

Non-Squamous NSCLC with Extensive Progression After EGFR-TKIs Treatment

Included in the "Expert Consensus on Management Strategies Following Resistance to Third-Generation EGFR-TKIs(2023 Edition)"