World Lung 2023 – some support for TROP2 combos in first-line lung cancer

While PD-(L)1-relapsed lung cancer is the big stage for follow-on immuno-oncology drugs, with AstraZeneca/Daiichi Sankyo’s datopotamab deruxtecan recently underwhelming in the Tropion-Lung01 trial, there's a tussle to improve on Keytruda in the first-line setting too. At World Lung yesterday Gilead’s Trodelvy, the TROP2-targeted ADC rival to datopotamab, seemed promising in the Evoke-02 trial, its Keytruda combo yielding an ORR of 69% in first-line patients with ≥50% PD-L1 expression. It’s hard to tell what the best cross-trial comparator is now, but in Merck & Co’s Keynote-024 an ORR of 45% backed the 2016 approval of Keytruda in ≥50% PD-L1-expressing front-line NSCLC. Datopotamab itself also yielded first-line data, an Imfinzi combo in Tropion-Lung04 showing ORR of 50% irrespective of PD-L1 expression. Like in the Keytruda-combo Tropion-Lung02 trial, adding chemo to the doublet increased remission rates further and added toxicity. Trodelvy has been outplayed by Enhertu in breast cancer indication, so NSCLC offers some hope of redemption, and the Evoke-02 data were said to back the pivotal first-line Evoke-03 trial, which focuses on ≥50% PD-L1 expressers. However, prospects for the second-line Evoke-01 study are less promising, results with an NSCLC cohort in Tropics-03 having never been revealed, presumably because they underwhelmed.

Selected NSCLC trials of anti-TROP2 ADCs

Note: *Infinzi combo, all others use Keytruda. Source: clinicaltrials.gov.