Better late than never for Datroway in lung cancer

AstraZeneca and Daiichi’s Datroway U-turn in non-small cell lung cancer has paid off: the TROP2-targeting ADC has just gained US accelerated approval for second-line EGFR-mutated disease. This is a narrower niche than the second-line non-squamous market the partners had once been aiming for, but it’s a good result given the thumbs up was largely based on an uncontrolled phase 2 trial, Tropion-Lung05.

It’s also a victory in Datroway’s long-running battle against Gilead’s rival TROP2 ADC, Trodelvy, which was abandoned in second-line NSCLC following the failure of the Evoke-01 trial. This was despite Gilead’s best efforts to file Trodelvy based on a subset of Evoke-01 patients who never responded to PD-(L)1 blockade – which apparently got short shrift from the FDA.

Thus it seems the regulator has been more lenient with Astra and Daiichi, although the subgroups in question are different.

First line battle

The battleground now turns to the bigger opportunity of first-line NSCLC, where both projects are in phase 3 – Trodelvy in the Evoke-03 study, testing a Keytruda combo in patients with PD-L1 expression of 50% or greater.

Datroway is in various first-line trials, including the analogous Tropion-Lung08. Another contender here could be Merck & Co and Kelun’s sacituzumab tirumotecan, with a couple of first-line studies ongoing amid its huge pivotal programme.

Notable trials of TROP2 ADCs in first-line NSCLC

Note: *Merck-sponsored global trials; Kelun also carrying out Asian-focused trials. Source: OncologyPipeline & clinicaltrials.gov.

Meanwhile, Astra and Daiichi can boast of having the only FDA approved TROP2 ADC for lung cancer. The accelerated nod was based on a 45% overall response rate among 114 patients with EGFR mutations in the aforementioned Tropion-Lung05 trial (77 patients) and the phase 3 Tropion-Lung01 study (37 patients).

The confirmatory trial will be Tropion-Lung15, testing Datroway with or without Tagrisso, versus chemo, in second-line EGFR-mutated NSCLC. The primary endpoint is progression-free survival, and data are expected next year.

The companies had once hoped for approval in second-line non-squamous NSCLC, but pulled a filing here last November; even this was a narrower focus than once hoped, after Tropion-Lung01 failed to show a benefit in squamous disease.

Datroway got the FDA nod in second-line ER-positive, HER2-negative breast cancer in January, despite the phase 3 Tropion-Breast01 study only showing statistically significance in PFS, and not OS.

Astra has predicted peak Datroway sales of over $5bn.

Datroway’s US approvals

Source: OncologyPipeline, company releases.