Roche blows open the lung cancer competition
Investors had increasingly seen Roche’s Impower-150 trial in first-line lung cancer as a long-shot, based on the company’s dialling back of expectations. But this morning the study read out positively on progression-free survival, blowing the immuno-oncology field wide open once again and lifting Roche's shares by 6%.
There are subtleties to the result in what is ultimately a complex trial, but the data will give Merck & Co particularly a headache, given the recent delay to Merck’s Keynote-189 readout. And if Impower-150 has just established a new treatment combination Roche’s hand will be particularly strong in Europe.
This is because, unlike Merck’s Keytruda chemo combo in the US, no checkpoint inhibitor has yet been approved for first-line NSCLC in the EU. If Impower-150 results are good enough for regulators – Roche says US and EU submissions are imminent – Tecentriq could become the first to get this prized front-line EU label.
Roche said that the PFS benefit was statistically significant for Tecentriq plus Avastin plus chemo versus Avastin plus chemo, keeping the actual data back for December’s Esmo I-O congress. The company also said that a still immature OS analysis was “encouraging”.
The next OS analysis will take place in the first half of next year; while an eventual OS advantage is by no means certain, bulls will point to Merck’s small Keynote-021G study, whose Esmo update showed OS developing positively versus a previous analysis at Asco.
It is not clear what the EU might deem approvable, having sent Merck back to the drawing board when the company tried to submit Keytruda on the back of Keynote-021G. It was remission data in Keynote-021G that got Keytruda its US accelerated approval for first-line NSCLC, and an approval-friendly FDA will likely give Tecentriq the thumbs up too.
So, if Roche’s potential advantage in the EU is clear, what does the Impower-150 PFS hit mean in the US?
Firstly it establishes Tecentriq plus Avastin’s advantage over Avastin – the US standard of care for non-squamous NSCLC patients, and a higher bar than Alimta, against which Keytruda plus chemo is being compared. Secondly, it gives Roche a strong commercial advantage if the two therapies can be bundled. It could even help shield Avastin against the threat of biosimilars.
And Merck’s ability to counterattack has already been weakened: last month the company said readout of its confirmatory Keynote-189 trial would be delayed until early 2019 after OS was promoted to a co-primary endpoint.
|Selected upcoming 1st-line NSCLC trial readouts|
|Study||Active treatment||Comparator||Data||Trial ID|
|Checkmate-227 (part 1A)||Opdivo + Yervoy in PD-L1+ves||Chemo||Mid-2018 (Asco?)||NCT02477826|
|Checkmate-227 (part 1B)||Opdivo + Yervoy or chemo in PD-L1-ves||Chemo||Mid-2018||NCT02477826|
|Mystic (OS data)||Imfinzi (+ tremelimumab)||Chemo||H1 2018 (Asco?)||NCT02453282|
|Impower-150 (OS data)||Tecentriq (+ Avastin) + chemo||Avastin + chemo||H1 2018||NCT02366143|
|Impower-130||Tecentriq + chemo||Chemo||2018||NCT02367781|
|Checkmate-227 (part 2)||Opdivo + chemo in all-comers||Chemo||Late 2018||NCT02477826|
|Neptune||Imfinzi + tremelimumab||Chemo||H2 2018||NCT02542293|
|Keynote-189||Keytruda + chemo||Chemo||Feb 2019||NCT02578680|
Whatever the outcome, Impower-150 reading out positive at this first analysis is unexpected, as evidenced by Roche’s share price climb today. Just last week the group was hinting at PFS missing significance, pointing to recent I-O readouts and perhaps taking its cue from Astrazeneca’s Mystic trial.
And the fact that the positive result came in all comers eliminates the importance of analysing patients’ PD-L1 expression. Roche also said there was a PFS benefit – presumably particularly strong – in patients with a T-effector gene signature, but again since the overall trial was positive this novel biomarker can perhaps be ignored.
As such, Impower-150 has become less complex (Event – The next showdown in first-line lung cancer, September 13, 2017). One thing still not revealed is the comparison of Tecentriq plus chemo versus Avastin plus chemo, though Roche did state that only the Tecentriq/Avastin/chemo comparison was powered for significance.
The Tecentriq plus chemo comparison will be intriguing, because it can suggest how much better anti-PD-L1 therapy is over Avastin. And an exploratory across-arm look at the triple combo versus Tecentriq plus chemo can hint at how much of the benefit comes courtesy of Avastin.
Other unknowns include safety, in particular the rate of thrombocytopenia in the triple combo arm, said Evercore ISI’s Umer Raffat, who also shrugged off the threat to Merck, saying Impower-150 provided incremental validation for I-O/chemo regimens as a whole.
Investors were unconvinced, sending Merck off 2% this morning. Keytruda might have first-mover advantage, but if Roche just showed the superiority of its own combo against a true standard of care then Merck really does have something to worry about.