World Lung 2023 preview – Astra’s Tagrisso showdown

Investors won’t have much time to rest after the summer break, with the next big industry conference, World Lung, kicking off on 9 September. Most abstracts from this went live yesterday, but the one that didn’t, covering AstraZeneca’s Flaura2 study, could generate the most interest.

This is because it’s of huge importance to Johnson & Johnson, as well as to Merus and Blueprint, in indicating the correct comparator in first-line EGFR-driven NSCLC. There are several other presentations to note too, and with Daiichi Sankyo’s ADCs on display the Japanese group will want to shake off the recent disappointment of datopotamab deruxtecan’s Tropion-Lung01 trial.

Dato is an anti-TROP2 ADC Daiichi is developing with AstraZeneca, but topline results from Tropion-Lung01, a pivotal trial in second-line NSCLC patients against docetaxel, knocked confidence. The July release was cautiously worded, calling a PFS improvement “statistically significant” but not saying it was clinically meaningful, omitting any numbers, and revealing “some grade 5 events”.

World Lung will see data from the phase 1 Tropion-Lung04 trial in the first-line Imfinzi-combo setting, seen by analysts as less important for dato’s immediate prospects. The results might also be compared against Tropion-Lung02, a broadly similar study that used Merck & Co’s Keytruda instead of Imfinzi.

Also in the mix is the similar Evoke-02 trial of Gilead’s Immunomedics-derived rival TROP2 ADC Trodelvy, which has underwhelmed in its approved indication of breast cancer, but for which NSCLC offers some hope of redemption. Similarly, for Trodelvy the key near-term NSCLC setting is second line, where the Evoke-01 trial versus docetaxel ends next May.

The big one

For Flaura2, however, World Lung has reserved a prime spot: the data will be presented at a presidential session on 11 September, and are still under embargo.

The trial concerns front-line EGFR-mutant NSCLC, a space effectively owned by Tagrisso, adding chemo on top of the Astra drug and comparing this combo against Tagrisso alone. In May it was toplined positive for PFS.

This is a space J&J wants to get into with Rybrevant plus lazertinib via the Mariposa trial, but a possible problem is that Mariposa uses Tagrisso as the comparator. Not only did Mariposa already pass interim analysis without being halted for efficacy, even if it succeeds a strong showing in Flaura2 might render the Tagrisso monotherapy comparator obsolete.

Scrutiny at World Lung will fall on the size of Flaura2’s PFS benefit, and it should be noted that nothing is yet known about its overall survival figures. Full data will also be important for Merus and Blueprint, which are gunning for first-line NSCLC trials of MCLA-129 (EGFR x cMET bispecific) and BLU-945 (EGFR inhibitor) respectively.

Selected World Lung 2023 presentations

Note: *approved in China for T790m NSCLC; **registrational trial for US approval, where the FDA has set 27 Nov 2023 PDUFA date. ADC=antibody-drug conjugate; TCE=T-cell engager; TKI=tyrosine kinase inhibitor.

Also in the EGFR-mutant NSCLC space, South Korea’s Bridge Biotherapeutics will present data on BBT-176 that from the abstract look fairly uninterpretable, while Allist/ArriVent’s furmonertinib, marketed in China for T790m-positive disease, has data in the separate setting of exon 20 insertion. Bradley Canino, an analyst at Stifel, reckons Black Diamond’s BDTX-1535, which recently impressed, remains the leading fourth-generation small-molecule EGFR inhibitor. 

Among MAb approaches Daiichi will have data on its HER3-targeting ADC patritumab deruxtecan in patients who have already failed an EGFR-targeting small molecule. And, with a separate presentation on the low-profile ADC against B7-H3, ifinatamab deruxtecan, World Lung is set to be quite the conference for the Japanese group.

The IASLC World Conference on Lung Cancer takes place in Singapore on 9-12 September.