Esmo preview – Novel checkpoints add to the Parp showdown

While the texts of oral and late-breaking Esmo abstracts are under wraps until next week, today’s unveiling of the meeting’s poster presentations has given investors a few more showdowns to look forward to. These include AstraZeneca and Pfizer’s Ox40 agonists, and the leading checkpoint inhibitors in urothelial carcinoma.

The data add to Esmo’s most keenly awaited confrontations, including those between Clovis, Medivation, Astra and Tesaro’s Parp inhibitors (see table below). The top places at the meeting’s late-breakers have also been confirmed, though bizarrely one of the most important studies has been edged out of the press programme by Oncogenex’s failed Affinity trial.

That prostate cancer study, the latest in a litany of flops for Oncogenex’s custirsen, failed in August despite an earlier protocol change. Yet it features not only as a late-breaker at the third of Esmo’s presidential sessions, but also in the special press programme on Monday.

Hopefully Esmo, which in previous years has given special treatment to failures like GlaxoSmithKline’s Mage-A3 vaccine, is encouraging lessons to be learned from disaster. However, Affinity’s inclusion comes at the expense of Bristol-Myers Squibb’s failed Checkmate-026 first-line NSCLC trial – one of the meeting’s hottest tickets.

Bristol is expected to detail essential findings regarding Opdivo’s efficacy in patients with different levels of PD-L1 expression (Bristol swings for the fences and strikes out, August 5, 2016). Two of Opdivo’s checkpoint inhibitor competitors, Merck & Co’s Keytruda and Roche’s Tecentriq, star in their own NSCLC late-breakers, though the latter’s Oak trial is in second-line use.

Hot Parps

Failure also features in the area of Parp inhibition, where the Gold trial of AstraZeneca’s Lynparza in advanced gastric cancer has a Saturday late-breaker spot.

After Pfizer’s $14bn takeout of Medivation interest in Parp inhibitors has grown, and investors will also be focusing on data to be presented at Esmo from the Ariel2 study of Clovis’s rucaparib, and the Nova trial of Tesaro’s niraparib, in ovarian cancer.

Other mechanisms of interest include CDK4/6 inhibition, where Novartis’s ribociclib is squaring up to Pfizer’s marketed breast cancer drug Ibrance. The Esmo late-breaker concerns first-line use of ribociclib plus letrozole in HR-positive, Her2-negative breast cancer – likely the Monaleesa-2 study that was halted early for efficacy in May.

Selected Esmo 2016 presentations
Date Project Company Study Trial ID Abstract
7 Oct KTE-C19 Kite Zuma-1 NCT02348216 1048O
7 Oct Selinexor Karyopharm NCT02025985 854O
7 Oct Prexasertib Lilly/Array NCT02203513 855O 
7 Oct Rucaparib Clovis Ariel2 NCT01891344 856O
7 Oct ANG1005 Angiochem NCT02048059 324O
8 Oct Ribociclib Novartis Monaleesa-2 NCT01958021 LBA1_PR
8 Oct Opdivo Bristol-Myers Squibb Checkmate-275 NCT02387996 LBA31_PR
8 Oct Keytruda Merck & Co Keynote-052 NCT02335424 LBA32_PR
8 Oct Niraparib Tesaro Nova NCT01847274 LBA3_PR
8 Oct Lynparza AstraZeneca Gold NCT01924533 LBA25
8 Oct Talazoparib Pfizer (Medivation) NCT02282345 153PD
8 Oct CRLX101 Cerulean NCT02389985 864P
9 Oct Opdivo Bristol-Myers Squibb Checkmate-026 NCT02041533 LBA7_PR
9 Oct Keytruda Merck & Co Keynote-24 NCT02142738 LBA8_PR
9 Oct Opdivo Bristol-Myers Squibb Checkmate-141 NCT02105636 LBA4
9 Oct Tecentriq Roche Oak NCT02008227 LBA44_PR
9 Oct Xtandi Medivation/Pfizer Premiere NCT02288936 726PD
9 Oct NY-ESO-1 Adaptimmune NCT01343043 1075P
9 Oct Ipafricept Bayer/Oncomed NCT02050178  367PD
9 Oct Cometriq + Opdivo Exelixis/BMS NCT02496208 774PD
9 Oct Lirilumab + Yervoy Innate Pharma/BMS NCT01592370 1086P
10 Oct Custirsen Oncogenex Affinity NCT01578655  LBA9_PR
10 Oct Cotellic + Tecentriq Exelixis/Roche NCT01656642 1109PD
10 Oct Epacadostat + Keytruda Incyte/Merck & Co Keynote-037 NCT02178722 1110PD
10 Oct Avelumab Pfizer/Merck KGaA Javelin Solid Tumor NCT01772004 777PD
10 Oct MEDI0562 AstraZeneca NCT02318394 1052PD
10 Oct PF-04518600 Pfizer NCT02315066 1053PD

Among the abstracts that have already been made available, Pfizer and Merck KGaA’s avelumab is contesting the first approved use of Roche’s Tecentriq – urothelial carcinoma. Early data relate only to 109 patients with over four months’ follow-up, showing three complete and 15 partial remissions.

Opdivo and Keytruda are making challenges of their own in this cancer type – their respective Checkmate-275 and Keynote-052 trials have late-breaker slots. And data will also be presented from Opdivo’s Checkmate-141 head and neck cancer trial, halted for efficacy in January before swift US and EU filings in this cancer.

Of course, Esmo is not all about PD-1/PD-L1 inhibitors. Among the unveiled abstracts is a first-in-human trial of Pfizer’s Ox40 agonist, PF-04518600, showing just one partial remission (PR) in 25 patients, while Astra’s rival MEDI0562 has shown one PR in 19 evaluable patients.

Elsewhere, Incyte’s IDO1 inhibitor epacadostat has shown a 58% ORR in 19 first-line melanoma patients in the Keynote-037 combination trial with Keytruda. Other trials suggest the viability of combining Innate Pharma’s lirilumab with Bristol’s Yervoy or Opdivo, though the Esmo abstract mainly details the combos’ toxicity profiles.

Still, the much bigger event for Innate investors is the monotherapy trial Effikir, in AML, whose results are imminent. Likewise, Kite Pharma investors now know that full data from the Zuma-1 interim readout toplined this week will not come until the ASH meeting in December, so the Esmo update of Zuma-1’s phase I portion might be purely academic.

Robin Davison will report from the Esmo meeting on October 7-11. He can be followed on @RobinDavison2EP Vantage has also produced a free backgrounder ahead of the meeting, highlighting recent breakthroughs, setbacks and approaching data points.

To contact the writer of this story email Jacob Plieth in London at jacobp@epvantage.com or follow @JacobPlieth on Twitter

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