GSK makes haste while Daiichi struggles

While the struggles of Daiichi Sankyo and its partners to overcome the lung toxicity of deruxtecan-containing antibody-drug conjugates continue, at least one of their competitors is pressing full-steam ahead. GSK has just revealed plans to take the B7-H4-directed ADC mocertatug rezetecan into its first two western pivotal studies this year.

True, that’s not a direct comparator for Daiichi’s latest problem, the Merck & Co-partnered ifinatamab deruxtecan, whose Ideate-Lung02 trial is on global hold, but which targets B7-H3, not B7-H4. But, while Daiichi has no disclosed anti-B7-H4 ADCs in the pipeline, GSK is notable for also recently having taken a separate B7-H3-directed molecule, risvutatug rezetecan, into phase 3.

GSK licensed both risvuta-R and mocerta-R from China’s Hansoh Pharma, which earlier advanced the two ADCs into Chinese pivotal studies. GSK’s pivotal move with risvuta-R marked that project’s first western phase 3 study, and took place last August – not long before Daiichi and Merck quietly implemented a global clinical hold over ifinata-dxd’s Ideate-Lung02 trial.

B7-H4

As for the B7-H4-directed mocerta-R, that entered a Hansoh-sponsored phase 3 trial last March, in platinum-resistant ovarian cancer.

Now come mocerta-R’s first western phase 3 trials, both sponsored by GSK, and both due to begin this March. The first is also in platinum-resistant ovarian cancer (Behold-Ovarian01), while the second is called Behold-Endometrial01, and concerns endometrial cancer patients who have received one or two prior lines of systemic treatment.

Both studies will compare mocerta-R monotherapy against physician’s choice chemo. Behold-Ovarian01 is very similar to Hansoh’s Chinese phase 3, except that it additionally features the choice of gemcitabine in the control arm, and tests PFS and OS co-primary endpoints; Hansoh’s study has a sole primary endpoint, PFS.

The two new trials make mocerta-R appear to be the industry’s most advanced anti-B7-H4 ADC. The next-furthest advanced molecule is probably AstraZeneca’s puxitatug samrotecan, which has been taken into phase 3 (the Bluestar-Endometrial01 study began last August) after a long delay to reporting phase 1/2 results.

One key difference between Bluestar-Endometrial01 and the new Behold-Endometrial01 is that the Astra trial mandates B7-H4 expression on patients’ cancers. Behold-Endometrial01 appears to make no such stipulation, though patients’ B7-H4 status must be known before randomisation.

New phase 3 studies of mocertatug rezetecan

Note: PROC=platinum-resistant ovarian cancer. Source: OncologyPipeline.