Emergence of a next-generation lung cancer targeted drug?

Positive research results on next-generation lung cancer-targeted therapies are presented one after another

J INTS BIO, BridgeBio confirms response rates…Voronoi discloses new clinical trial results

Black Diamond enters Phase II trial overseas... Boehringer Ingelheim also confirms the possibility of early clinical trials

Clinical trials on 4th generation non-small-cell lung cancer targeted therapies by domestic and international pharmaceutical and biopharmaceutical companies are progressing smoothly.

 

J INTS BIO, Voronoi, Therapex, and BridgeBio are continuing their development making clinical success.

 

Among global pharmaceutical companies, Blue Diamond has entered Phase II clinical trials, and it has been confirmed that Boehringer Ingelheim has shown efficacy with its candidate in preclinical trials.

 

Korean companies make research results studying next generation lung cancer targeted therapies

According to industry sources on the 12th, J INTS BIO recently announced the results of a Phase I, high-dose clinical trial of JIN-A02, which is being developed as a treatment for epidermal growth factor receptor (EGFR) positive non-small-cell lung cancer (NSCLC).

 

JIN-A02, a fourth-generation EGFR tyrosine kinase inhibitor (TKI), has a mechanism of action that selectively binds to the C797S mutation that causes resistance to third-generation treatments for non-small cell lung cancer.

 

In clinical trials, high doses (300 mg) of JIN-A02 did not cause any serious adverse reactions or dose-limiting toxicity.

 

To date, JIN-A02 has shown partial response (PR) in 1 patient and stable disease (SD) in 3 patients in clinical trials.

 

J INTS BIO explained that this is the first case of a PR in a patient with the C797S mutation among the fourth-generation EGFR-TKI treatments currently being developed in Korea and abroad.

 

Currently, the first-generation EGFR-positive lung cancer drugs on the market include AstraZeneca's Iressa (gefitinib) and Roche's Tarceva (erlotinib), the second-generation drugs include Boehringer Ingelheim's Giotrif and Pfizer's Vizimpro (dacomitinib), and third-generation drugs, Yuhan Corp’s Leclaza (lasertinib) and AstraZeneca's Tagrisso (osimertinib).

 

However, resistance inevitably develops even with the use of effective targeted therapies.

 

A typical mutation that occurs with EGFR-positive targeted therapies is C797S.

 

In addition, patients lack treatment options to use after targeted therapies.

 

Platinum-based chemotherapy, docetaxel, and immune checkpoint inhibitors are available for patients who develop resistance to targeted therapies.

 

Still, there has been no significant improvement in their response rates with their subsequent use.

 

To address the need, latecomers such as J INTS BIO, have set a goal of confirming the possibility of commercialization by targeting the C797S mutation that occurs after patients develop resistance to existing 1st- to 3rd-generation targeted therapies.

 

Voronoi will present the early clinical results of VRN11 at the American Association for Cancer Research (AACR) Annual Meeting 2025, which will be held next month.

 

According to Voronoi, VRN11 is effective not only against EGFR C797S acquired resistance mutations, but also against common mutations such as EGFR Del19 and L858R, and atypical mutations such as EGFR G719X, L861Q, and S768I.

 

Voronoi recently changed the clinical protocol for VRN11.

 

The company has received approval from the Ministry of Food and Drug Safety to change the clinical trial protocol expand the size of the Phase I clinical trial from 50 to 103 patients and significantly increase the dose escalation rate and target.

 

BridgeBio is exploring the safety and efficacy of BBT-207, which is being developed as a 4th-generation EGFR-positive non-small cell lung cancer treatment, in a Phase I dose-escalation trial.

 

At the recent meeting of the Safety Monitoring Committee, the efficacy and safety of the drug were evaluated by analyzing data from 6 patients enrolled in the fifth dose group of the BBT-207 Phase 1 clinical trial.

 

In the above, BBT-207 did not cause any serious adverse drug reactions, and 3 cases of partial response (PR) and several stable disease (SD) cases were observed.

 

Therapex recently announced the clinical design and interim results of the first cohort of ‘TRX-221,’ a 4th-generation EGFR-targeted anticancer drug for non-small cell lung cancer.

 

TRX-221 is a 4th-generation EGFR tyrosine kinase inhibitor that selectively inhibits EGFR C797S as well as EGFR activating mutations and T790M mutations.

 

Currently, Therapex is conducting a Phase Ia clinical trial on TRX-221 at 6 university hospitals in Korea, including Asan Medical Center, Severance Hospital, and Samsung Medical Center.

 

The company has been administering the drug to patients in the second cohort since early September.

 

Therapex plans to conduct global clinical trials, including in the United States, to expand patient recruitment during the dose development phase.

 

Black Diamond makes the most progress in development...

 

Boehringer also shows its candidate’s potential in preclinical trials Black Diamond Therapeutics has made the most progress in the global pharmaceutical industry.

 

Black Diamond Therapeutics has observed the most PRs with its 4th generation EGFR TKI candidate in the Phase I/II trial.

 

Black Diamond Therapeutics is developing BDTX-1535, which had been developed as a treatment for brain tumors, as a 4th generation lung cancer targeted therapy.

 

According to the results of the Phase II clinical trial that have been disclosed so far, 8 out of 19 patients (42%) treated with the 200 mg dose of BDTX-1535 showed an objective response rate (ORR).

 

Five of the responding patients showed a confirmed partial response (PR), one of whom converted from a PR to an unconfirmed complete response (CR) at the 8-month time point.

 

The safety assessment showed that the 200 mg dose was well tolerated, consistent with previous clinical results.

 

The majority of adverse events were mild or moderate, with rash (70%) and diarrhea (35%) being the most common adverse reactions.

 

There were two cases of Grade 3 rashes, but no Grade 4 rash or Grade 3/4 diarrhea were observed.

 

In particular, Black Diamond explained that its candidate showed promising therapeutic effects in patients who developed resistance after treatment with Tagrisso.

 

Black Diamond plans to update the Phase II clinical trial data within the second quarter of this year.

 

Boehringer Ingelheim is developing BI-4732 as a 4th generation-targeted therapy.

 

It is currently in the preclinical stage.

 

Domestic researchers, including Byoung Chul Cho, director of the Lung Cancer Center at Yonsei Cancer Center, are participating in this clinical trial.

 

In clinical trials that have been disclosed so far, BI-4732 has recorded a cancer cell growth inhibition rate of up to 183% in animal models transplanted with cell lines derived from patients with the triple mutations of exon 19 deletion, T790M, and C797S.

 

This was up to 2.6 times higher than that of Tagrisso.

 

The development of 4th generation lung cancer-targeted therapies is also underway in China.

 

Chinese companies Betta Pharmaceuticals and Chia Tai Tianqing are conducting Phase I clinical trials of BPI-361175 and TQB-3804, respectively.