On September 8, 2024, Kangfang Biotechnology announced at the 2024 World Lung Cancer Congress the heavyweight research data of the registered Phase III clinical trial (HARMONI-2/AK112-303) of the company's independently developed global first PD-1/VEGF bispecific antibody new drug, Ivoxidan, compared to pembrolizumab monotherapy for the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with PD-L1 expression positive (PD-L1 TPS ≥ 1%). Ivoxidan became the world's first drug to demonstrate significantly better efficacy than pembrolizumab in a single drug head to head Phase III clinical trial. Affected by this news, the stock price of Kangfang Biotechnology has risen by 14%.

AK112-303/HARMONI-2 (CTR20222137) is a registered phase III randomized, double-blind clinical trial conducted in China to evaluate the first-line treatment of locally advanced or metastatic NSCLC with PD-L1 expression positive (PD-L1TPS ≥ 1%) compared to Ibuprofen (PD-1/VEGF) monotherapy. The primary endpoint was PFS assessed by IRRC according to RECIST v1.1, and the secondary endpoints were OS, ORR, DoR, and safety. A total of 398 subjects were enrolled.

The research results show that:

ITT population analysis: HR=0.51 mPFS 11.14 months

Yiwoxi first-line treatment for PD-L1 positive NSCLC significantly prolonged the median progression free survival (mPFS) of patients compared to pembrolizumab, with both statistical and clinical significance.

In the ITT population, the mPFS of the ivoxil group and the pembrolizumab group were 11.14 months and 5.82 months, respectively; PFS HR=0.51 (P<0.0001), and the risk of disease progression/death was reduced by 49% in the treatment group with Ecovacil.

Compared with pembrolizumab, Ecovacil significantly improved the objective response rate (50.0% vs 38.5%) and disease control rate (89.9% vs 70.5%) of first-line treatment for PD-L1 positive NSCLC patients, demonstrating the highly effective anti-tumor effect of Ecovacil.

As of this publication, the overall survival (OS) data for HARMONI-2 is not yet mature.

Subgroup analysis: In each subgroup population, Ivosi significantly benefited

In subgroups with different levels of PD-L1 expression, the efficacy of Ecovacil was more significant.

The proportion of PD-L1 TPS ≥ 50% patients enrolled in the HARMONI-2 study was 42.2%, which is consistent with the distribution of the real-world population. In the population with PD-L1 TPS ≥ 50%, the PFS HR of bevacizumab compared to pembrolizumab was 0.46, and the risk of disease progression/death was reduced by 54%. In the PD-L1 TPS 1-49% population, the PFS HR of ivoxil compared to pembrolizumab was 0.54, and the risk of disease progression/death was reduced by 46%.

In both the squamous cell carcinoma and non squamous cell carcinoma subgroups, the efficacy of ezetimibe was more significant.

The proportion of squamous non-small cell lung cancer patients included in the HARMONI-2 study was 45.5%, while the proportion of non squamous non-small cell lung cancer patients was 54.5%, which is consistent with the distribution of the real world population. In the population of squamous non-small cell lung cancer, the PFS HR of bevacizumab compared to pembrolizumab is 0.48. In the population of non squamous non-small cell lung cancer, the PFS HR of bevacizumab compared to pembrolizumab is 0.54.

Regardless of whether there is liver metastasis, brain metastasis, etc., the efficacy of Ecovacil is more significant.

In this study, 12.6% of patients received treatment with Ivosi for liver metastasis and 16.7% for brain metastasis.

Compared with pembrolizumab, the PFS HR for patients with brain metastases treated with Ecovacil was 0.55, and the PFS HR for patients without brain metastases was 0.53. Compared with pembrolizumab, the PFS HR of patients with liver metastases treated with Ivosi was 0.47; The PFS HR for treating patients without liver metastasis is 0.53.

Safety: Ecovaci has excellent overall safety, and all subgroups maintain consistency

In the HARMONI-2 study, 72.2% of squamous cell carcinoma patients treated with ezetimibe were central type, 10.0% of patients had tumors with cavities or necrosis, and 6.7% of patients had tumors surrounding important blood vessels. These patient populations are contraindicated for traditional anti VEGF treatment, and the risk of bleeding with ezetimibe treatment did not significantly increase compared to the control group. The research results show that Ecovacil has excellent overall safety, consistent with previous related studies.

In the population of squamous non-small cell lung cancer, the incidence of TRAE ≥ 3 grade was comparable between bevacizumab and pembrolizumab (22.2% vs 18.7%). The overall quality of life of patients receiving Ivosi treatment is comparable to those receiving pembrolizumab treatment.

Based on the positive results of this study, the company's partner SUMMIT has also announced plans to conduct the HARMONI-7 study to evaluate a global multicenter phase III clinical trial of the first-line treatment of PD-L1 overexpressing (PD-L1TPS>50%) metastatic NSCLC using Ivoxidan versus Pabolizhu monotherapy.

Ecovacil has become the world's first and only drug to demonstrate significant efficacy over pembrolizumab in single agent head to head phase III clinical trials. In August 2024, the marketing application (sNDA) for the new indication of Yvoxi was accepted by the National Medical Products Administration (NMPA) of the People's Republic of China and included in the priority review. Yiwoxi has become a new standard treatment option for advanced NSCLC lung cancer patients with positive PD-L1 expression in the first-line treatment, offering a better treatment option of "chemotherapy free".

Yida Fang (Yiwoxi) is a globally pioneering PD-1/VEGF bispecific tumor immunotherapy drug independently developed by the company. Yida Fang was approved by NMPA on May 24, 2024 for the treatment of locally advanced or metastatic non squamous NSCLC with EGFR mutations that have progressed after EGFR TKI therapy. At present, Yiwoxi has been approved for one indication in China, and eight phase III clinical trials are underway, including two international multicenter phase III trials conducted overseas and six phase III clinical trials using PD - (L) 1 monoclonal antibody as a positive control drug. Currently, more than 25 clinical trials covering 17 indications, including gastrointestinal tumors, hepatocellular carcinoma, and colorectal cancer, are underway at Yvoxi.

Source: https://pharm.jgvogel.cn/c1441343.shtml