K-pharma trials show greenlight overcoming bile duct cancer

Handok's US partner Compass Therapeutics has confirmed ORR in Phase 2/3 clinical trials

HLB shows the potential of rivoceranib combination therapy…overseas development is also active

South Korean and the overseas pharmaceutical industry's candidate products that are targeted anticancer agents for bile duct cancer (cholangiocarcinoma) are showing results of effectiveness, indicating the potential for commercialization possibilities.

 

Korean and overseas pharmaceutical companies, including Handok's US partner Compass Therapeutics and HLB, are challenging this area.

 

Compass "tovecimig met primary endpoint in global clinical trials" #iAccording to industry sources on April 3, US-based Compass announced top-line results from tovecimig's COMPANION-002 Phase 2/3 trial evaluating patients with metastatic or recurrent cholangiocarcinoma.

 

Tovecimig is a novel drug candidate for cholangiocarcinoma, which was developed by the Korean company ABL Bio.

 

Handok holds domestic commercialization rights, and Compass holds global rights.

 

This new drug candidate is a dual antibody that simultaneously targets delta-like ligand 4 (DLL4) and vascular endothelial growth factor (VEGF), thereby inducing neovascularization in the tumor microenvironment.

 

The study enrolled 168 adult patients with metastatic or recurrent cholangiocarcinoma and compare the efficacy and safety of the tovecimig+paclitaxel combination therapy versus paclitaxel monotherapy.

 

The clinical trial results showed that the primary endpoint, objective response rate (ORR), was 17.1% in the tovecimig+paclitaxel group, compared to only 5.3% in the paclitaxel monotherapy group.

 

Furthermore, the incidence of progressive disease (PD) was 16.2% in the combination group versus 42.1% in the monotherapy group.

 

Regarding safety, Grade ≥3 adverse events observed in the Phase 2 trial were consistent with previous studies.

 

These included neutropenia (50%), hypertension (16.7%), anemia (12.5%), and thrombocytopenia (8.3%).

 

There was one reported case of Grade 5 pneumonia, and 25% of patients discontinued treatment due to adverse events such as confusion, pulmonary embolism, and elevated blood creatinine levels.

 

Handok plans to utilize these results as supporting data for regulatory approval of tovecimig in Korea.

 

Following these top-line findings, Compass intends to present additional data, including key secondary endpoints, from the COMPANION-002 trial later this quarter.

 

Compass also supports a researcher-led clinical trial evaluating tovecimig as a first-line therapy for cholangiocarcinoma, in addition to the ongoing COMPANION-002 study.

 

This trial, led by the MD Anderson Cancer Center at the University of Texas, investigates the efficacy and safety of adding tovecimig to the standard regimen of Imfinzi plus chemotherapy.

 

Rivoceranib shows potential in cholangiocarcinoma Cholangiocarcinoma is considered one of the most challenging solid tumors due to its low survival rate and the limited availability of new targeted therapies.

 

Although the patient population is relatively small compared to other cancers, early diagnosis remains difficult, and the disease is characterized by rapid metastasis and recurrence to surrounding organs, resulting in a 5-year relative survival rate of only 28.9% (2017–2021).

 

Reports indicate that 7 out of 10 cholangiocarcinoma patients eventually die, and the domestic mortality rate in Korea is estimated at 11.6%.

 

Another reason for low survival rate is the scarcity of effective treatment options.

 

For patients with locally advanced or metastatic cholangiocarcinoma who are not candidates for surgery and have failed first-line therapy, there is a critical lack of second-line options.

 

Although the development of various targeted therapies was possible for cholangiocarcinoma, like lung cancer, limited patient numbers have restricted research and investment.

 

However, growing interest from the pharmaceutical industry is now yielding promising research outcomes.

 

Handok

Handok has recently expanded the therapeutic landscape by introducing two targeted treatments in Korea: its FGFR2-targeted therapy 'Pemzayre' and Servier’s IDH1-targeted therapy 'Tipsovo.' Other Korean and overseas companies are venturing into this field.

 

FGFR genetic abnormalities are known to contribute not only to cancer cell proliferation, survival, and migration but also to tumor angiogenesis and drug resistance.

 

Meanwhile, IDH1 mutations are predominantly found in gliomas and cholangiocarcinomas, with a particular prevalence in intrahepatic cholangiocarcinoma.

 

In addition to Handok, Korean company HLB is actively investigating new treatment options for cholangiocarcinoma.

 

HLB, in collaboration with Hangseo Pharmaceuticals, is evaluating the clinical efficacy of a combination regimen comprising the VEGFR2 inhibitor riboceranib and the immuno-oncology agent camrelizumab in several solid tumors, including liver cancer and cholangiocarcinoma.

 

In a clinical study conducted over approximately two years beginning in January 2021, 28 patients with advanced cholangiocarcinoma were treated with riboceranib combination therapy, administered either as a first-line or second-line treatment.

 

The trial demonstrated a median overall survival (OS) of 12.8 months and a median progression-free survival (PFS) of 6.3 months, nearly double the typical 6- to 7-month survival period seen in patients with inoperable cholangiocarcinoma.

 

Notably, among patients who received riboceranib combination therapy as first-line treatment, the ORR was 50.0%.

 

HLB plans to review additional investigator-led clinical data from this study to further expand its pipeline.

 

New drug R&D for cholangiocarcinoma is active globally

China's TransThera Sciences is currently conducting a Phase 3 clinical trial in cholangiocarcinoma patients, with studies underway not only domestically but also in the United States, the United Kingdom, China, and other regions.

 

Tinengotinib is a next-generation FGFR inhibitor designed for advanced cholangiocarcinoma patients harboring FGFR mutations who have prior treatment history.

 

According to TransThera Sciences, this multi-kinase inhibitor features a unique FGFR binding mechanism that bypasses acquired resistance pathways.

 

Clinical trial results showed that tinengotinib is effective in patients with advanced cholangiocarcinoma harboring FGFR mutations who have previously received systemic chemotherapy.

 

In the clinical trial, patients were categorized into four groups based on their FGFR mutation status and treatment history.

 

▲Group A1 (13 patients): Patients with FGFR2 fusions whose disease progressed following treatment with conventional FGFR inhibitors ▲Group A2 (10 patients): Patients with FGFR2 fusions who initially responded to conventional FGFR inhibitors but subsequently relapsed ▲Group B (12 patients): Patients with non-fusion FGFR mutations ▲Group C (13 patients): Patients with no FGFR mutations (FGFRwt).

 

Eisai has recently launched its FGFR2 inhibitor, Tasfygo, in Japan, boldly entering the cholangiocarcinoma market.

 

In a Phase 2 study, Tasfygo achieved an ORR) of 30.2% (90% CI: 20.7–41.0), statistically surpassing the pre-set tumor response threshold of 15%.

 

Meanwhile, U.S.-based Jazz Pharmaceuticals plans to launch its HER2-targeted therapy, 'Ziihera,' globally.

 

Jazz Pharmaceuticals secured the development rights for Ziihera from U.S.

 

biotech company Zymeworks in 2022 and has been conducting clinical studies.

 

Accelerated approval was granted for this therapy in the U.S.

 

last November, and it is now positioned to expand into international markets, including Korea.

 

Its basis of approval HERIZON-BTC-01, Ziihera demonstrated an ORR of 52% with a duration of response (DOR) of 14.9 months.