As soon as Bavencio’s Javelin Renal 101 trial yielded an unexpectedly strong topline result the question everyone wanted answered was whether an abstract could be submitted for Esmo by the September 17 deadline. Last week investors got their answer as the study appeared in the Esmo late-breakers.
When the meeting gets under way in Munich on October 19 the full results will be scrutinised to ascertain just how big a threat they are for Exelixis – déjà vu for the biotech group, which faced a similar challenge from Bristol-Myers Squibb at Esmo 2017. Beyond that Tecentriq’s Impassion-130 readout in breast cancer will get attention, as will numerous combination studies.
For now only the presentation titles have been unveiled by Esmo. Most abstracts will remain under wraps until October 9, oral presentation texts will not be revealed until midday of the meeting’s first day, and the embargo on late-breakers will not lift until the start of the session in which each is presented.
This presages an anxious wait for Exelixis investors, who a year ago saw their group’s first-line renal cancer results in the Cabosun study overshadowed by late-breaking presentation of data from Bristol-Myers Squibb’s Checkmate-214. Now Javelin Renal 101 threatens something similar (Pincer movement squeezes Exelixis in kidney cancer, September 12, 2018).
Javelin Renal 101 is among several pivotal trials whose results have been toplined but whose full data have been kept for Esmo and have been selected for the meeting’s plenary session, called the presidential symposium.
Two other such trials are Impassion-130, the most advanced immunotherapy trial in triple-negative breast cancer, which has read out positively for progression-free survival, and Solo-1, which in June made Lynparza the only Parp inhibitor to show a PFS benefit in first-line maintenance treatment of BRCA1/2-mutated ovarian cancer.
Also sure to get its share of attention will be the Keynote-048 study of Keytruda in first-line squamous head and neck cancer. The Merck & Co drug is already approved second line, as is Bristol’s Opdivo, while Astra’s Imfinzi had its own first-line study, Kestrel, briefly put on clinical hold.
|Selected Esmo 2018 presentations|
|Javelin Renal 101||Bavencio + Inlyta||Pfizer/Merck KGaA||LBA6_PR||1st-line renal carcinoma, positive for PFS in all comers|
|Impassion-130||Tecentriq||Roche||LBA1_PR||1st-line triple-negative breast cancer, positive for PFS|
|Solo-1||Lynparza||Astrazeneca||LBA7_PR||Maintenance ovarian BRCA1/2 mut ovarian cancer, positive for PFS|
|Keynote-048||Keytruda||Merck & Co||LBA8_PR||1st-line squamous head & neck cancer, positive for OS|
|Solar-1||Alpelisib||Novartis||LBA3_PR||HR+/Her2- PI3KCA mut breast cancer, positive for PFS|
|Finesse||Lucitabin||Clovis||289PD||HR+ Her2- metastatic breast cancer; Servier handed back rights Aug 2018|
|NCT02150967||Infigratinib||Bridgebio Pharma||LBA28||Selective pan-FGFR kinase inhibitor, licensed from Novartis|
|NCT02825836||M7583||Merck KGaA||1014PD||First-in-human trial, BTK inhibitor in B-cell malignancies|
|Keynote-200||Cavatak||Merck & Co||LBA40||Oncolytic virus acquired with Viralytics, Keytruda combo|
|MK-1308-001||MK-1308||Merck & Co||414PD||Externally sourced anti-CTLA-4, combo with Keytruda|
|Keynote-202||BL-8040||Biolinerx||1133PD||Keytruda combo in metastatic pancreatic adenocarcinoma|
|NCT02923531||X4P-001-RD||X4/Sanofi||1134PD||Opdivo combo in renal cell carcinoma unresponsive to Opdivo monotherapy|
|MK-1454-001||MK-1454||Merck & Co||LBA15||First-in-human study of Sting activator, monotherapy or Keytruda combo|
|NCT02492789||INCSHR1210||Jiangsu Hengrui/Incyte||LBA27||Anti-PD-1 MAb, 2nd-line hepatocellular carcinoma|
|NCT02627274||RG7461||Roche||412PD||Anti-FAP MAb-IL2 fusion protein, single-agent cohort|
|NCT02264678||AZD6738||Astrazeneca||413PD||ATR serine/threonine kinase inhibitor, Imfinzi combo|
|Paloma-3||Ibrance||Pfizer||LBA2_PR||OS data (secondary endpoint), known to be negative|
Away from the limelight of presidential symposia Merck will also feature in two presentations of assets it has bought in.
Keynote-200 showcases Keytruda combined with Cavatak, an oncolytic virus it had acquired along with the Australian company Viralytics in February. Oncolytic virus approaches are seeing increasing interest on account of their combination potential, and have generated significant business development activity.
And the “externally sourced, internally refined” anti-CTLA-4 asset MK-1308 will feature in an early trial combining it with Keytruda. Liver cancer data for another asset derived externally, Incyte’s anti-PD-1 MAb INCSHR1210, could generate interest, especially now that a sixth PD-(L)1 asset – Sanofi/Regeneron’s Libtayo – has secured US approval.
The spotlight will, of course, fall on combinations in general, notwithstanding the blow of this year’s failure of Incyte’s epacadostat in Echo-301. Keynote-202, for instance, combines Biolinerx’s BL-8040 with Keytruda, and is among the industry’s most advanced pancreatic cancer studies.
That and several other immuno-oncology studies in patients unresponsive to prior checkpoint blockade could show whether these combos have any potential, and will ensure that Esmo is relevant not only for big pharma followers.