ECC preview – Incyte and NewLink pull curtain back on IDOs

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For all the partnership manoeuvring that has marked the early-stage immuno-oncology space known as IDO inhibition there has been precious little evidence of how well it will work in humans – until now.

Incyte and NewLink Genetics are set to reveal detailed data on their projects at the European Cancer Congress starting next week in Vienna, with early signs of efficacy disclosed for the former company’s INCB24360 in combination with Yervoy. More mature immuno-oncology projects will also take the stage, with Roche’s atezolizumab featured as a late-breaking presentation in bladder and lung cancers.

IDO believe that is your cue

IDO inhibition, for indoleamine 2,3-dioxygenase, has been an area of interest for 18 months since Merck & Co put it on the map with a non-exclusive deal to combine it Keytruda (Merck tries to climb back into PD-1 combo race, February 6, 2014).

This pathway modulates T-cell response to tumours; it is believed that inhibition of this enzyme with small molecules could improve the body’s ability to fight cancer much as the checkpoint inhibitor antibodies Keytruda, Opdivo and Yervoy do, and that it will work well in combination.

At the ECC Incyte is disclosing data from a phase I/II dosing study of its agent, now known as epacadostat, in melanoma combined with Bristol-Myers Squibb’s Yervoy, the first checkpoint inhibitor. At the data cutoff, the combination achieved a disease control rate of 60% using response evaluation criteria in solid tumours standards.

The abstract for NewLink’s trial of indoximod with Yervoy in melanoma is less revealing, only disclosing safety data for the phase Ib dose escalation part of the trial as of April 26. Updated results, including potentially response data similar to Incyte’s, are expected when the group makes its poster public on September 26.

Both companies’ work in IDO inhibition is well known to big pharma, with epacadostat having been part of numerous non-exclusive deals with Roche, Bristol-Myers Squibb, AstraZeneca and Merck, and NewLink having been signed up by Roche for its next-generation agent in a full licence. 

Roche to the fore

At the late-stage end of the spectrum, the ECC meeting looks to be big for the third antibody working on the PD-1/PD-L1 pathway, Roche’s atezolizumab, which will have data from three separate trials in the spotlight.

Data in bladder cancer, in which it first made a splash at Asco in 2014, and in several lung cancer treatment lines will be closely scrutinised by oncologists during oral presentations. The Swiss group expects to submit regulatory filings imminently in both indications.

The Birch trial as a first-line therapy and Poplar in second and third-line treatment will cover non-small cell lung cancer in phase II, while IMVigor is a phase III using atezo as an adjuvant treatment in bladder cancer following cystectomy.

Oncologists will get an uncommon side-by-side comparison of checkpoint inhibiting antibodies against small-molecule alternatives when Exelixis’s Cometriq and Bristol’s Opdivo will feature late-breaking presentations in renal cell carcinoma; both were tested against Afinitor (Bristol rains on Exelixis’s parade, July 20, 2015).

Checkpoint inhibitors are not the only advanced therapies that will be featured at oral sessions: Amgen’s oncolytic virus talimogene laherparepvec, or T-Vec, might show its promise as a combination therapy with readout of data from the Masterkey-265 trial with Keytruda in advanced melanoma, though the abstract's headline only mentions safety data.

Cancer vaccines are not dead yet, either. Immatics Biotechnologies' IMA901, a multipeptide agent, will have data from its phase III trial in which it was combined with Sutent – the privately held group has not disclosed any results on this programme. The German group has recently partnered with MD Anderson to develop T-cell receptor therapies, so it has many cards to play should the data be negative – and will likely be making return trips to this and other oncology meetings.

Company Project Trial Abstract
Roche atezolizumab Birch NCT02031458
Poplar NCT01903993
IMVigor NCT02450331
16LBA
14LBA
21LBA
Incyte epacadostat NCT01604889 511
NewLink Genetics indoximod NCT02073123 514
Bristol-Myers Squibb Opdivo Checkmate 025 NCT01668784 3LBA
Exelixis Cometriq Meteor NCT01865747 4LBA
Immatics Biotechnologies IMA901 NCT01265901 17LBA

To contact the writer of this story email Jonathan Gardner in London at jonathang@epvantage.com or follow @ByJonGardner on Twitter

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