World Lung preview – small-cell showdown

When the World Congress on Lung Cancer kicks off in Toronto later this month all eyes will be on Roche’s Impower-133 study.

The inroads that immuno-oncology has made into non-small cell lung cancer have highlighted how intractable the rarer small-cell disease still is. So limited has progress been that topotecan and amrubicin-containing chemo are still standards for treating SCLC.

This makes the unveiling of Roche’s Impower-133 study of Tecentriq the highlight of this month's World Lung conference. Unusually for an anti-PD-(L)1 study this first-line SCLC trial is known to have read out positively for progression-free as well as overall survival, and disclosure of the magnitude of the benefit will be keenly awaited.

The abstract is set to feature at the conference’s plenary session on September 25, and its content is embargoed until then. Doctors will also be keen to pick apart the full dataset for trends as to PD-L1 status and other biomarkers.

Featuring on Monday, and separately embargoed, is another Tecentriq study, Impower-132. This tests the Roche drug in first-line NSCLC in combination with Alimta, and thus is analogous to the Keynote-189 study of Keytruda, on the basis of which the Merck & Co drug secured full approval as a chemo combo in all non-squamous patients.

However, Impower-132 read out positively for PFS but not OS. Moreover, the US FDA has delayed by three months its review of Tecentriq’s first-line NSCLC filing, as part of an Avastin and chemo combo based on the Impower-150 trial, until December 5.

While a third setting, stage III, non-metastatic NSCLC, also features in the plenary courtesy of Astrazeneca’s Pacific study of Imfinzi, this could see less attention; since Imfinzi has already secured this use on its US label disclosure of the study’s numerical OS benefit will probably be the main point of interest.

Given that Imfinzi is the only immuno-oncology drug to have made progress in stage III disease the spotlight could fall on a rival study: an investigator-initiated trial of Keytruda in this setting is to be presented at World Lung on September 24. However, Merck has yet to reveal its path forward here.

Best of the rest

It would be unusual for immuno-oncology not to feature strongly at World Lung, and other data of interest involve mesothelioma, with trials of Keytruda as well as of Bristol-Myers Squibb’s rival, Opdivo.

Follow-on projects feature too, notwithstanding the fact that they are now coming very late to the party: Sanofi/Regeneron’s cemiplimab, already filed for cutaneous squamous cell carcinoma, features in a NSCLC abstract. And the failed second-line Javelin Lung 200 study of Merck KGaA/Pfizer’s Bavencio will be picked apart, though the real focus remains first-line use, where it is being evaluated in the Javelin Lung 100 trial.

It is not all about biologicals, of course. Pharmamar’s Zepsyre is battling for a place in second-line SCLC, and keenly awaited data from a single-arm phase II trial will be used to handicap chances of success in its placebo-controlled phase III Atlantis study. This could also help drum up enthusiasm as Pharmamar seeks a US ADS listing.

The World Lung abstract features 27 subjects given the same Zepsyre plus chemo regimen used in phase III, and the company will make a strong case that the 7.9 months of OS reported in this trial so far bode well against historical data. Still, data cited at Asco put the benefit right in topotecan’s six to nine-month zone (Asco 2018 – Small cell lung data underwhelm but big readouts approach, June 5, 2018).

First-line checkpoint blockers like Tecentriq threaten to shake up the second-line market further. The Zepsyre abstract, like those of Opdivo, Bavencio and cemiplimab, is a placeholder with an early data cut, and up-to-date numbers will be released at World Lung itself.

The same goes for the presentation of Loxo’s LOXO-292, while Roche’s entrectinib paper is embargoed until September 24. The two assets, targeting Ret and Ros1 mutations respectively, form part of a resurgent targeted approach against specific genetically defined subtypes of NSCLC.

And what would a lung cancer conference be without a focus on combination therapy? A major session will take place on September 26 covering IO combos with IO, chemo, targeted agents and radiotherapy. The catastrophic failure of IDO inhibition has only slightly dampened enthusiasm, it seems.

Selected presentations from 2018 World Congress on Lung Cancer 
Product Study Setting Detail Abstract
Tecentriq Impower-133 1st-line SCLC (+ve for OS & PFS) Embargoed until 25 Sep PL02.07
Zepsyre NCT01970540 2nd-line SCLC 27 pts given chemo combo regimen P1.12-20
Imfinzi Pacific Stage III NSCLC, OS data (PFS known) Embargoed until 25 Sep PL02.01
Keytruda NCT02343952 Stage III NSCLC Investigator-initiated trial OA01.07
Tecentriq Impower-132 1st-line NSCLC, Alimta combo (missed OS) Embargoed until 24 Sep OA05.07
Cemiplimab NCT02383212 Phase I NSCLC expansion cohorts In ph III for NSCLC MA04.01 
Bavencio Javelin Lung 200 2nd-line NSCLC Failed study OA05.05 
Keytruda NCT02399371 2nd-line mesothelioma Investigator-initiated trial OA08.03
Opdivo Merit Opdivo in mesothelioma Long-term Japan data OA08.01 
Alunbrig Alta-1L 1st-line Alk+ NSCLC, vs Xalkori Embargoed until 25 Sep PL02.03
LOXO-292 Libretto-001 Ret+ NSCLC Apr data cut - placeholder OA12.07
Entrectinib Startrk-2 Ros1+ NSCLC Embargoed until 24 Sep OA02.01 
Poziotinib NCT03066206 EGFR & Her2 mutant NSCLC May data cut - placeholder OA02.06
TILs NCT03215810 Opdivo combo 9/14 pts had had progressed on Opdivo OA05.03
CK-101/RX518 NCT02926768 EGFR+ NSCLC Jun data cut - placeholder OA02.05
Various Various IO-IO combinations Tim3, Vista, Lag-3, Tigit, Ox40, Gitr, CD137, CD27 MS28.02

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