CSPC looks for HER2 white space

The battle of the Chinese anti-HER2 x HER2 ADCs just ratcheted up a notch, with CSPC recently starting a phase 3 study of its contender anbenitamab repodatecan in colorectal cancer, according to a new listing on clinicaltrials.gov.

The big name in this target is AstraZeneca and Daiichi’s Enhertu, but in colorectal specifically the competition looks closer to home: Chia Tai also has a HER2 x HER2-targeting biparatopic ADC, rolditamig deuderuxtecan, and this also recently began a Chinese phase 3 in this setting, although it has yet to appear on the US trial registry.

Enhertu, a monoparatopic anti-HER2 ADC, is approved in China for breast, lung and gastric cancers. In the US the drug also has a tumour-agnostic label for patients with relapsed HER2-positive cancers and no satisfactory alternative treatment options, based heavily on data in colorectal cancer.

Therefore Enhertu has set a benchmark in this tumour type, although CSPC and Chia Tai are going after a new use, in China at least.

Face-off

CSPC’s new study, known as JSKN003-005 and with a start date of 6 February, will test anbenitamab repodatecan versus investigator’s choice in second-line, HER2-positive colorectal cancer. Patients are required to have previously failed on oxaliplatin, 5-fluorouracil and irinotecan and, in the case of dMMR and MSI-high disease, PD-(L)1 inhibitors. The primary endpoint is progression-free survival.

Chia Tai’s trial, which was listed on the China drug trials database in January, will enrol HER2-positive patients who have previously been treated with oxaliplatin, irinotecan, or fluorouracil-based therapies. Patients will receive either rolditamig deuderuxtecan, previously known as TQB2102, or investigator’s choice.

In terms of setting expectations, the data so far in this tumour type have varied. In a phase 1/2 solid tumour trial presented at last year’s ESMO meeting, CSPC's anbenitamab repodatecan produced an overall response rate of 69% among 32 efficacy-evaluable HER2-positive colorectal cancer patients. 

Chia Tai has claimed an ORR of 35% with rolditamig deuderuxtecan in HER2-high colorectal cancer in a phase I solid tumour trial presented at ASCO 2025. Meanwhile, among 64 HER2-overexpressing colorectal cancer patients receiving Enhertu in the Destiny-CRC02 study, which supports the drug's tumour-agnostic approval, the ORR was 47%.

Breast cancer

Both anbenitamab repodatecan and rolditamig deuderuxtecan are already in various other Chinese phase 3 trials, although Chia Tai has so far focused on breast cancer, while CSPC has also brought platinum-resistant ovarian cancer into the mix. 

Breast cancer is an established use for Enhertu, both in China and elsewhere, so going up against it could be a tough task, especially since the Astra/Daiichi drug was added to the China’s state-run insurance list from January 2025.

By hitting two different HER2 epitopes, biparatopic ADCs are designed to improve binding and internalisation, which could reduce toxicity and increase efficacy. However, it’s still unclear whether this approach really has an edge, with Zymeworks discontinuing its western contender, zanidatamab zovodotin, in 2024.

CSPC licensed its candidate from Alphamab in mainland China in September 2024. Other HER2 x HER2 ADCs in development include Xuanzhu Biopharmaceutical’s KM501, although a Chinese phase 1 with a start date of 2023 is still listed on clinicaltrials.gov as “not yet recruiting”; and preclinical-stage dual payload projects from Hangzhou DAC (DXC018) and Phrontline Biopharma (TJ106).

Chinese phase 3 trials of CSPC & Alphamab’s anbenitamab repodatecan

Notes: HER2+ve=IHC 3+, or IHC 2+ & ISH+ve; HER2-low=IHC 1+, or IHC 2+ & ISH-ve. Source: OncologyPipeline & clinicaltrials.gov.