Esmo preview – A Merck versus Bristol showdown

There is still a month to go before abstracts for the European Society of Medical Oncology’s annual meeting are revealed, but it looks like late-breakers featuring Keytruda and Opdivo in lung cancer will give biopharma investors the most to look forward to.

And there is more, with Pfizer’s recent $14bn takeout of Medivation bringing into play Esmo presentations on Tesaro and Clovis’s rival Parp inhibitors. The presentation titles are now available, showing how this, plus data on novel immuno-oncology combinations, could kickstart biotech after the summer lull (see table below).

Investors enjoying a relaxing holiday already had one jolt with the shock failure of Bristol-Myers Squibb’s Opdivo in first-line lung cancer (Bristol swings for the fences and strikes out, August 5, 2016). Now they will look to Esmo, where full data from this trial, Checkmate-026, could provide essential information about Opdivo’s potential in patients expressing higher levels of PD-L1.

Bristol had designed the trial expecting a benefit in patients expressing PD-L1 at 5% or more, hoping then to expand the analysis to >1%, but the plan failed. In hindsight the group should have looked at patients with 30% or 50% expression levels, and investors will focus on these – now only exploratory – analyses.

Merck’s own, successful, front-line NSCLC trial of Keytruda, Keynote-024, looked at the smaller >50% PD-L1-expressing population. To rub salt into Bristol’s wound, full data from this trial, positive for progression-free and overall survival, could feature at another Esmo late-breaker, Leerink analysts say.

Combinations and more

The quest for novel immuno-oncology combos is a burgeoning area, and trials featuring Opdivo, Keytruda and Yervoy are sure to generate interest.

An NCI-sponsored phase I study of Cometriq, for instance, could elucidate the drug’s potential in combination with Opdivo and/or Yervoy in renal cancer, Leerink reckons, while another Exelixis drug, Cotellic, will show combo data with Roche’s Tecentriq in melanoma and in colorectal cancer.

Then there are novel immuno-oncology targets such as Ox40 – MAbs from AstraZeneca and Pfizer feature – and phase I data with Keytruda plus Incyte’s epacadostat, an IDO1 inhibitor.

Innate Pharma’s Bristol-partnered anti-KIR MAb lirilumab will feature in safety studies in combination with Opdivo or Yervoy. While lirilumab’s monotherapy Effikir study in AML remains a key trigger for Innate investors, with readout due this year, combinations represent the greatest chances of success, Leerink analysts write.

Selected Esmo 2016 presentations
Project Company Study Trial ID Abstract, date
Opdivo Bristol-Myers Squibb Checkmate-026 NCT02041533 LBA poss 7 Oct*
Keytruda Merck & Co Keynote-24 NCT02142738 LBA poss 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
Niraparib Tesaro Nova NCT01847274 LBA poss 7 Oct*
ANG1005 Angiochem NCT02048059 324O, 7 Oct
CRLX101 Cerulean NCT02389985 864P, 8 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, 9 Oct
Cotellic + Tecentriq Exelixis/Roche NCT01656642 1109PD, 10 Oct
Epacadostat + Keytruda Incyte/Merck & Co Keynote-037 NCT02178722 1110PD, 10 Oct
MEDI0562 AstraZeneca NCT02318394 1052PD, 10 Oct
PF-04518600 Pfizer NCT02315066 1053PD, 10 Oct
*Late-breakers subject to confirmation in early September.

The third major area of interest at Esmo will be Parp inhibitors, which until the launch of AstraZeneca’s Lyparza in 2014 were thought to be dead and buried. The key so far has been biomarkers, and interest has been stoked by the Medivation takeout.

Though Pfizer of course did not disclose how much of the $14bn valuation it attributed to Medivation’s talazoparib, this Parp inhibitor is reckoned to have contributed strongly to the knockout price. The Esmo presentation of data from two rival Parps, Tesaro’s niraparib and Clovis’s rucaparib, will thus be keenly awaited.

Though none of the late-breakers have been confirmed, full results of niraparib’s Nova trial in second-line ovarian cancer maintenance are likely to feature at one; data from the BRCA wild-type/HRD-negative subgroup could threaten talazoparib if they suggest potential in ovarian cancer patients without the BRCA mutation, Lynparza’s approved indication.

Clovis, which recently enjoyed a 20% share price jump on the mere FDA acceptance of its rucaparib filing for BRCA-mutated ovarian cancer, will feature in oral presentations of studies included in this submission (Clovis fights back into crowded Parp race, August 24, 2016). Talazoparib does not appear in any Esmo abstract titles.

There will also be plenty for followers of other small-cap and private biotechs, from presentations by Karyopharm, Corvus and Angiochem, for instance. Cell therapy will take a back seat, though presentations from Adaptimmune and Kite will serve as a springboard for December’s Ash meeting.

By that time Kite’c KTE-C19 might already have been filed with the FDA, presaging – as Kite bulls desperately hope – commercial approval of the first ever CAR-T therapy.

EP Vantage will publish further backgrounders before Esmo, and Robin Davison will report from the meeting on October 7-11. He can be followed on @RobinDavison2.

To contact the writer of this story email Jacob Plieth in London at [email protected] or follow @JacobPlieth on Twitter

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