Novel Checkpoints Add To The Parp Showdown

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Includes: AZN, BMY, CLVS, GSK, INCY, INNTY, KITE, MDVN, MRK, NVS, OGXI, PFE, RHHBY, TSRO
by: EP Vantage

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 (NYSE:AZN) and Pfizer’s (NYSE:PFE) Ox40 agonists, and the leading checkpoint inhibitors in urothelial carcinoma.

The data add to Esmo’s most keenly awaited confrontations, including those between Clovis (NASDAQ:CLVS), Medivation (NASDAQ:MDVN), Astra and Tesaro’s (NASDAQ:TSRO) 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 program by Oncogenex’s (NASDAQ:OGXI) 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 program on Monday.

Hopefully Esmo, which in previous years has given special treatment to failures like GlaxoSmithKline’s (NYSE:GSK) Mage-A3 vaccine, is encouraging lessons to be learned from disaster. However, Affinity’s inclusion comes at the expense of Bristol-Myers Squibb’s (NYSE:BMY) 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 (NYSE:MRK) Keytruda and Roche’s (OTCQX:RHHBY) 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’ 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

Click to enlarge
Click to enlarge

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 (NASDAQ:INCY) 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 (OTC:INNTY) 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 (NASDAQ:KITE) 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.

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