Esmo 2019 preview – Parps on parade
Among small-molecule approaches Europe’s premier oncology conference gives star billing to three Parp inhibitors in ovarian cancer.
With this weekend’s World Lung meeting still fresh in the mind oncology watchers will have no time to rest on their laurels. The next major conference, Esmo, is set to kick off just two weeks later, and it even takes place at the same venue in Barcelona.
True to recent form Esmo is continuing to make a push to outclass Asco as the world’s most important cancer meeting, something that largely depends on the timing of study readouts. All the abstract titles are now out, revealing late-breaker slots for numerous trials toplined in recent weeks, perhaps the most important of which is the Paola-1 study of Astrazeneca’s Parp inhibitor, Lynparza.
The investigator-sponsored trial, testing Lynparza in first-line ovarian cancer regardless of BRCA status, was reported last month to have read out positively for progression-free survival. This set up a battle between Astra and Glaxosmithkline’s Zejula, whose corresponding Prima trial, in the same setting, had been toplined as positive weeks earlier.
For now only the presentation titles have been unveiled by Esmo, and it can only be assumed that Prima will also feature. A late-breaker entitled “[Zejula] in ... newly diagnosed advanced ovarian cancer” features in the same session, and seems likely to relate to Prima, making this showdown the highlight of Esmo.
And Abbvie will present its own challenge with the Parp inhibitor veliparib, whose chemo combo first-line ovarian cancer maintenance trial Velia is the third late-breaker in this session. This project has failed in NSCLC and triple-negative breast cancer, but in a surprisingly low-key mention in July Abbvie said Velia was positive for PFS.
|Selected Esmo 2019 abstracts relating to small molecules|
|Friday, 27 September|
|Fight-202||Pemigatinib||Incyte||2L cholangiocarcinoma||Interim data at Esmo 2018||LBA40|
|Unspecified||Berzosertib||Merck KGaA||2L ovarian||ATR inhibitor||LBA60|
|Unspecified||AVB-S6-500||Aravive||2L ovarian||AXL kinase inhibitor||LBA59|
|Saturday, 28 September|
|Paola-1||Lynparza||Astrazeneca||1L ovarian maintenance irrespective of BRCA status||Toplined +ve for PFS Aug 2019||LBA2|
|Prima?||Zejula||Glaxosmithkline||1L ovarian maintenance irrespective of BRCA status (if Prima)||Prima toplined +ve for PFS Jul 2019||LBA1|
|Velia||Veliparib + chemo||Abbvie||1L ovarian maintenance irrespective of BRCA status||Toplined +ve for PFS Jul 2019||LBA3|
|Unspecified||Pamiparib||Beigene/Merck KGaA||Solid tumours||Parp 1/2 inhibitor||451PD & 452PD|
|NCT03600883||AMG 510||Amgen||KRAS G12C mutant solid tumours||NSCLC cohort @ World Lung||446PD|
|NCT02978716||Trilaciclib||G1 Therapeutics||TNBC||Claimed OS benefit Jun 2019||LBA22|
|Entrata||Telaglenastat||Calithera||Everolimus combo in 3L renal||Toplined +ve for PFS Jun 2019||LBA54|
|Trident-1||Repotrectinib||Turning Point||Ros1/TRK fusion+ve tumours||Lots of data revealed Sep 2019||444PD|
|Patriot||Ceralasertib||Astrazeneca||Solid tumours||ATR inhibitor||450PD|
|Sunday, 29 September|
|Brocade-3||Veliparib + chemo||Abbvie||Her2-ve, BRCA+ve breast||Toplined +ve for PFS Jul 2019||LBA9|
|Unspecified pivotal||LOXO-292||Lilly||Ret-altered thyroid||NSCLC data from Libretto-001 @ World Lung||LBA93|
|Meteor-1||GSK3326595||Glaxosmithkline/Epizyme||Solid tumours||PRMT 5 inhibitor||438O|
|Unspecified||INCB01158||Incyte/Calithera||Solid tumours||Arginase inhibitor||440O|
|Monday, 30 September|
|Invictus||Ripretinib||Deciphera||4L GIST||Lots of data revealed Aug 2019||LBA87|
|Gortec||Debio 1143||Debiopharm||Head & neck||Apoptosis protein inhibitor||LBA65|
The Parp inhibitors will therefore be at the forefront of the attack of small-molecule anticancer agents putting up a strong fight against the onward march of immunotherapy.
The most closely watched Esmo presentations featuring other targeted small molecules might be those relating to Amgen’s Kras inhibitor AMG 510 in various solid tumours, and Lilly’s LOXO-292 in Ret-altered thyroid cancer. NSCLC cohorts of both assets are set to feature at World Lung this weekend, and the former is of course of huge interest to followers of Mirati Therapeutics.
And four trials reported recently to have been positive will get full hearings at Esmo: Turning Point’s Trident-1 study of repotrectinib, Deciphera’s Invictus test of ripretinib, Calithera’s Entrata trial of telaglenastat, and G1 Therapeutics’ triple-negative breast cancer study of trilaciclib, claimed to be positive for overall survival.
Interestingly, plenty of data are already out relating to the first two. On Tuesday Turning Point unveiled a large amount of data from Trident-1, boasting a 91% ORR in tyrosine kinase-naive Ros1-positive NSCLC subjects, on the back of which it launched a $200m equity raise. This is all very well, but investors might not expect much more from Esmo itself.
Deciphera also has already disclosed much of the Invictus data, in GIST patients who had failed three or more treatment lines; its Esmo late-breaker might reveal more about how ripretinib performed in subjects with different baseline characteristics.
Read our second Esmo preview, focusing on immunotherapy.