Yuhan presents 4 studies at ASCO...builds reliability

[ASCO 2023] Poster presentations on the homegrown new drug Leclaza were made at ASCO 2023 on data in Korea and abroad

Phase I data on Leclaza+Rybrevant added...raises expectations for P3T

Reaffirms efficacy and safety in patients with brains metastasis

Yuhan Corp’s EGFR-targeting anticancer drug ‘Leclaza’ has started to accumulate data for the international stage.

 

At the ‘2023 ASCO Annual Meeting (ASCO 2023)’ that was held on the 2nd (local time), Yuhan Corp made 4 poster presentations on studies related to its Leclaza, including one long-term follow-up study.

 

With the results of Janssen’s main MARIPOSA study expected to be released in the second half of this year, initial research results that give a glimpse of the MARIPOSA study have also been updated.

 

Leclaza is a treatment for non-small-cell lung cancer that was approved as the 31st homegrown novel drug in January 2021.

 

It is a 3rd generation EGFR TKI that inhibits the proliferation and growth of lung cancer cells.

 

It is currently approved as a treatment for patients with locally advanced or metastatic NSCLC who developed resistance after being previously treated with 1st generation or 2nd generation EGFR-TKIs.

 

The drug had raised KRW 25 billion in sales in only 2 years of release.

 

The company is also awaiting to add a first-line indication to the drug.

 

Supported by such domestic growth, the company seeks to further its presence with Leclaza in the global market.

 

Janssen, which introduced Leclaza’s technology, is developing it as a combination therapy with Rybrevant, its EGFR bispecific antibody treatment.

 

The results of the MARIPOSA Phase III study, which looks at the drug’s effect of combination therapy in the first line, are expected to be announced soon.

 

Research data that provide a glimpse into the brain metastasis effect of Leclaza and the efficacy of Leclaza as a combination therapy were presented at this year’s ASCO.

 

First, the long-term follow-up results of the Phase I CHRYSALIS trial, which used EGFR exon 20 mutation treatment Rybrevant with Leclaza in EGFR-mutated NSCLC, were presented as a poster.

 

The CHRYSALIS trial was the first study to evaluate the efficacy of Rybrevant + Leclaza as a first-line treatment.

 

Long-term follow-up of Leclaza+Rybrevan combo (Data: ASCO)

After following 20 patients for 33.6 months, results showed that half of the patients were able to achieve progression-free survival.

 

At that time point, key indicators such as overall survival, progression-free survival, and duration of response had not yet reached median values.

 

Following the poster presentation, an oral presentation on the Cohort D data of the CHRYSALIS-2 study, which evaluated the safety of Leclaza + Rybrevant therapy or Leclaza monotherapy after treatment with Tagrisso, was made at the meeting.

 

The presented data were the results of the additional analysis conducted on biomarkers from the data that had been announced in 2021.

 

Subanalysis of Leclaza+Rybrevant combo according to presence of MET mutations (Data: ASCO)

The effect of combination therapy was significantly higher in the MET expression group.

 

The objective response rate (ORR) of the combination therapy in patients with MET mutations and amplification (28 patients) was 61%, which was higher than 14% in the MET-negative patient group (49 patients).

 

The median duration of response and median progression-free survival were 10.8 months and 12.2 months in the MET-positive group, respectively, compared to 6.8 months and 4.2 months in the MET-negative patient group.

 

A domestic phase 2 study that measured the effect of Leclaza in patients with brain metastasis after failure with existing first- and second-generation targeted anticancer drugs in EGFR-positive non-small cell lung cancer was also presented as a poster.

 

40 EGFR-positive patients with brain metastases after using first- and second-generation treatments were enrolled in the study to evaluate the intracranial activity of Leclaza in patients with asymptomatic or mild brain metastasis.

 

Patients who failed with conventional treatment were divided according to the presence or absence of the T790M mutation.

 

The primary evaluation index was intracranial objective response rate (iORR), and the secondary evaluation index was intracranial progression-free survival (iPFS).

 

The intracranial objective response rate of 38 evaluable patients was 55.3%.

 

3 patients showed a complete response and 18 patients showed a partial response.

 

There were only 5 T790M-positive patients, but 4 showed partial response, recording an intracranial response rate of 80%.

 

Of the 33 T790M-negative patients, 3 showed complete responses and 14 partial responses, recording an objective response rate of 51.5%.

 

The median overall progression-free survival and the progression-free survival in the T790M positive and negative groups were 15.2 months, 9.9 months, and 15.4 months, respectively.

 

Intracranial progression-free survival was similar for T790M positive and negative patients, 15.2 months and 15.8 months, respectively.

 

The research team said, “Leclaza showed significant intracranial activity regardless of the presence or absence of T790M mutation, and satisfied the primary evaluation index with an intracranial objective response rate of 55.3%." This indicates that patients that showed brain metastasis after treatment with targeted therapies may use lazertinib instead of topical treatment." In addition to this, studies that studied predictable biomarkers for the use of Rybrevant + Leclaza after Tagrisso were also announced at ASCO 2023.