Janssen makes first bid into lung cancer mkt with Rybrevant

Expectations rise on the expandability of Rybrevant

Janssen Korea hosts press conference to celebrate the launch of Rybrevant in Korea.

A new treatment option for patients with epidermal growth factor receptor (EGFR) exon 20 insertion mutation

Clinical trials on its combination therapy active in the field… explores Rybrevant’s potential in solid cancers

“We will work to make Rybrevant, which had been first approved to treat EGFR exon 20 insertion mutations, the No.1 option for lung cancer patients in Korea.” Janssen Korea expressed so at the press conference that was held on the 23rd to celebrate the launch of Rybrevant in Korea.

 

Rybrevant (amivantamab) received marketing authorization from the Ministry of Food and Drug Safety in February and was officially released this month.

 

As the first and only dual inhibitor that targets both the EGFR exon 20 insertion mutation and MET, the drug is approved for use in patients whose disease has progressed during or after platinum-based chemotherapy treatment.

 

According to the CHRYSALIS trial that became the basis of Rybrevant’s approval, the overall response rate (ORR) of the Rybrevant monotherapy-treated group was 40%.

 

4% of the participants achieved a complete response (CR), and 36% achieved a partial response (PR).

 

The median duration of response (DOR) was 11.1 months.

 

Based on such results, the National Comprehensive Cancer Network guidelines recommend Rybrevant as a treatment option for patients with EGFR exon 20 insertion mutation NSCLC after platinum-based chemotherapy treatment.

 

Professor Byoung-Chul Cho, Chief of Yonsei Cancer Center (Professor, Division of Medical Oncology, Yonsei Severance Hospital) who first identified the potential of Rybrevant in exon 20 insertion mutations, said, “While conducting a Phase I trial on lung cancer patients with Rybrevant, we found that the drug showed a dramatic effect in patients with exon 20 insertion mutations.

 

After identifying its potential through various preclinical trials, we quickly initiated the CHRYSALIS study to come up with results.” Exon 20 insertion mutations are present in around 10% of all patients with EGFR mutations.

 

Due to its various subtypes, patients with the mutation are unable to achieve desired results with existing EGFR-targeted cancer therapies.

 

Compared to the PFS of patients with common EGFR mutations (Exon 19 deletion, L868R) which was 11 months, the PFS of patients with Exon 20 insertion mutations was a mere 3 months.

 

The 5-year survival rate of patients with common EGFR mutations is 19%, but only 8% in patients with Exon 20 insertion mutations.

 

This was why the need for a new targeted therapy had been rising for the specific mutation.

 

Professor Cho believes that Rybrevant has a high potential to expand to other indications as it simultaneously targets both the EGFR and MET mutations and has a unique mechanism of action that activates immunity by engaging NK cells, monocytes, and macrophages.

 

Cho said, "Exon 20 insertion mutation presents in various subtypes.

 

Subgroup analysis results of the CHRYSALIS study showed that Rybrevant showed an even response across various subtypes.

 

Also, Rybrevant is promising as it has an immunological mechanism in addition to the target inhibition effect held by targeted therapies." Janssen Korea is also conducting various clinical trials to test the expandability of Rybrevant.

 

A Phase III trial in combination with chemotherapy and a Phase I study of Rybrevant monotherapy on MET exon 14 skipping mutation is underway.

 

The most anticipated combination is its combination with Leclaza (lazertinib) to target common EGFR mutations.

 

The company is conducting 3 clinical trials using the Rybrevant+Leclaza combination.

 

Two of the trials are Phase III trials, MARIPOSA-2, which identifies the potential of Rybrevant+Leclaza+chemotherapy as a treatment used after Tagrisso, and the MARIPOSA trial which directly compares Rybrevant+Leclaza to Tagrisso, is underway.

 

Also, Janssen Korea is exploring Rybrevant’s potential in various solid cancers including breast cancer and ovarian cancer.

 

Professor Cho said, “EGFR and MET are key targets that are commonly present in various other solid cancers as well.

 

The fact that Rybrevant is a bispecific antibody that inhibits both at the same time holds immense potential, and with the various clinical trials in progress, we may expect the drug to expand to other indications in the future.”