ESMO 2023 preview – J&J pulls a Mariposa rabbit out of the hat

Johnson & Johnson has followed swiftly on the doubts raised in AstraZeneca’s Flaura2 study with an unexpected apparent success in its own Mariposa trial. Not only that but, with organisers of ESMO bending over backwards to accept the data, investors will be able to see the full results as a late-breaker at that conference next month.

That’s one of many late-breaking abstracts whose titles ESMO surprisingly revealed this week for a conference that promises again to rival ASCO as the main venue for practice-changing trials. Other ESMO late-breakers include Astra/Daiichi Sankyo’s Tropion-Lung01 trial, and much will be needed to overcome the disappointment investors felt when that was toplined in July.

That so many recently toplined results like Mariposa have made it into ESMO seems surprising given that formally the meeting’s deadline for submitting finalised late-breaking abstracts was 14 September. Presumably for these last-minute readouts placeholders were submitted – and accepted.

Mariposa double

J&J will feature with not one but two late-breakers, with the Mariposa-2 study, toplined this month, joining Mariposa at a presidential session on 23 October.

Both studies concern combos of Rybrevant, an anti-EGFR x cMET bispecific MAb, with the third-generation EGFR inhibitor lazertinib, in EGFR-mutant NSCLC. Mariposa tested this front line, head to head against Astra’s blockbuster Tagrisso, and this was said yesterday to have hit on its primary endpoint of PFS, with a “trend” to a positive effect on overall survival at interim.

Astra’s Flaura2 study, profiled at World Lung, backed combining Tagrisso with chemo in these patients, but left enough open questions to make clear that Tagrisso monotherapy was the right Mariposa control arm. However, delays to Mariposa – J&J revealed in April that one interim analysis had been passed without a halt for efficacy – raised fears of an unconvincing result, so yesterday’s news came as a positive surprise.

Questions to be answered at ESMO include how big and meaningful the PFS benefit is, whether this alone could back approval, and how much toxicity such a dual combo brings. The trial also included lazertinib monotherapy, and, though this alone was not expected to beat Tagrisso, any info on how it performed will be vital to ascertaining lazertinib’s contribution to the doublet’s efficacy.

A similar question hangs over Mariposa-2, a second-line study in post-Tagrisso patients in which adding either Rybrevant alone or with lazertinib on top of chemo beat chemo alone on PFS – with nothing yet known about whether the triplet outperformed the Rybrevant/chemo doublet. 

Selected ESMO late-breakers featuring lung cancer

The same presidential session will also feature Astra/Daiichi’s Tropion-Lung01 trial of datopotamab deruxtecan – a study whose cautiously worded toplining had caused alarm. Were the data clinically meaningful after all, and how worrying is the occurrence of deaths due to interstitial lung disease?

Investors will also be looking forward to scrutinising Bristol Myers Squibb’s Checkmate-77T trial of Opdivo in perioperative NSCLC, toplined positive just a week ago, as well as the Dellphi-301 study of Amgen’s tarlatamab in small-cell lung cancer said to have yielded encouraging ORR data in August.

Dellphi-301 is important because it might back approval of tarlatamab, an anti-DLL3 T-cell engager, a mechanism with much baggage after the prominent failure of AbbVie’s Rova-T. Given bispecifics’ issues with cytokine release syndrome toxicity will also be closely watched.

Finally, among lung cancer late-breakers, the presence will be noted of GSK’s small Perla study, which in low-key fashion showed Jemperli to have beaten Keytruda on ORR and PFS in first-line NSCLC. ESMO promises to reveal the OS numbers, and Jemperli scoring here would be the icing on the cake.

The ESMO congress takes place in Madrid, Spain on 20-24 October. Full late-breaker texts will be published on 18 October.