Henlius starts a pivotal journey to catch Pfizer

Two companies, Pfizer and Shanghai Henlius, are targeting PD-L1 with ADCs, and with both now advancing their programmes into pivotal development early differences between the two approaches in terms of both strategy and data are becoming evident.

Pfizer is more advanced, with fetrastobart vedotin, but Henlius has been moving quickly to catch up: since presenting data last year on HLX43, the company has announced plans for four new pivotal lung cancer trials, and the first has just been posted on clinicaltrials.gov. While Pfizer is focused on monotherapy, for example, Henlius is also to investigate combinations.

EGFR combo

Henlius's first pivotal trial, HLX43-NSCLC302, is a global phase 2/3 expected to enrol 671 patients with squamous non-small cell lung cancer who must have progressed after previous anti-PD-(L)1 treatment; they will be tested for PD-L1 expression and EGFR expression. 

The design is somewhat similar to Pfizer's study, although the Pad1ink-005 trial of fetrasto-V will enrol a broader NSCLC population, including squamous and non-squamous histologies. Patients will need PD-L1 expression of at least 1%, and those with actionable genomic alterations are permitted but must have previously been treated with a targeted therapy. 

The differences do not end there. Pfizer is so far only testing its PD-L1 ADC as monotherapy, while HLX43-NSCLC302 will evaluate both monotherapy and a combination with Henlius's EGFR targeting antibody HLX07. 

Pfizer previously had two anti-PD-L1 ADCs, but discontinued one earlier this year. The remaining, Seagen-originated fetrasto-V has already been recruiting patients for several months into a pivotal trial. 

Unclear backing

To some extent Henlius's pivotal strategy is backed by phase 1/2 results on HLX43 reported last November, though that dataset lacked clarity. This involved pooled Chinese and global trials, but for patients with squamous histology the company only reported data for 2.0mg/kg (15% ORR), while in non-squamous disease it only disclosed results for 2.5mg/kg (ORR 26%).

The company also highlighted a 40% response rate in patients with PD-L1 expression of less than 1%, something that Pfizer could not achieve, as it reported zero responses for fetrasto-V in that population; however, the Chinese company didn't say how many of the claimed responses were confirmed. 

That signal could point to a greater bystander effect with HLX43, which might also translate into a more problematic safety profile; one patient treated at 2.5mg/kg died from treatment-related respiratory failure. Four cases of grade 3 interstitial lung disease were also reported.

Proof-of-concept data from the combo with HLX07 are expected this year, and this will give a clearer picture of how HLX43 plus HLX07 could perform in its new pivotal trial. 

Anti-PD-L1 ADCs in second-line NSCLC

Source: OncologyPipeline.