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
Study Project Company Setting Note Abstract
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.

A second Esmo preview, focusing on immunotherapy, will be published next week.

For live updates from the meeting, in Barcelona between September 27 and October 1, follow @ByAmyBrown and @JacobPlieth on Twitter.

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