AACR preview – Novel targets in the spotlight

The annual meeting of the American Association for Cancer Research has steadily been gaining in importance, and when its latest instalment kicks off in New Orleans next month investors will be watching particularly for initial data from novel cancer immunotherapy mechanisms.

These include first-in-human results for Roche and Amgen’s respective Ox40 agonist and anti-CSF1R MAb (see table below). More established anti-PD-1/PD-L1 MAbs will feature too, and in cell therapy a major symposium on April 19 will focus on CAR-T, while Kite will provide more data on its most advanced engineered T-cell receptor project.

The most advanced checkpoint inhibitor results concern overall survival data from Bristol-Myers Squibb’s Opdivo/Yervoy combo in melanoma, though this is an approved use. For novel indications look to survival results from Bristol’s Checkmate-141 – a head and neck cancer trial that was stopped early for efficacy in January.

Approval in head and neck cancer would further extend Opdivo’s lead over Merck & Co’s Keytruda, which features at AACR in a presentation of Keynote-006, a trial in first-line melanoma irrespective of Braf status – an approved indication as of December.

And, as new indications go, Keytruda data in Merkel cell carcinoma will also be presented; this rare cancer type might be the first indication for Merck KGaA/Pfizer’s avelumab, which will itself be the subject of results from the Javelin study in solid tumours.

Selected AACR abstracts
Project Company Notes Trial ID Abstract
Keytruda vs Yervoy Merck & Co Keynote-006, 1st-line melanoma NCT01866319 CT004
Keytruda Merck & Co Merkel cell carcinoma NCT02267603 CT096
Opdivo Bristol-Myers Squibb Checkmate-141, squamous head & neck cancer NCT02105636 CT099
Avelumab Merck KGaA/Pfizer Javelin Solid Tumor study NCT01772004 CT132
Axalimogene filolisbac Advaxis Listeria-based therapy before robotic surgery  NCT02002182 LB-095
Beigene-283 Merck KGaA Raf/Ras mutated tumours NCT02610361  CT005
Entrectinib Ignyta TKI-naive pts harbouring gene rearrangement NCT02097810  CT007
Loxo 101 Loxo Oncology Solid tumours with NTRK gene fusions  NCT02122913 CT008
RG7888 (MOXR0916)  Roche 1st in human Ox40 agonist NCT02219724 CT097
AM0010 Armo Biosciences Pegylated IL-10 NCT02009449  CT098
AMG 820 Amgen 1st in human anti-CSF1R MAb NCT01444404  CT137
JNJ-61610588 Johnson & Johnson Anti-Vista MAb NCT02671955  ?
AZD0156 AstraZeneca 1st in class ATM kinase inhibitor NCT02588105 ?
MBG453 Novartis Anti-Tim3 MAb NCT02608268 ?
Various CAR-Ts Juno, Novartis etc CAR T Cells: New Models in the Showroom Several Major symposium
KTE-C19 Kite Zuma-1 NCT02348216 CT135
CD22 CAR-T NCI Relevant to Juno NCT02315612 ?
Mage A3 TCR Kite Metastatic cancer, HLA-A1-positive pts NCT02153905 CT003
huEGFRVIII Novartis Glioblastoma NCT02209376    LB-083
EBV-CTL Atara EBV-associated nasopharyngeal carcinoma NCT00002663 CT136

For new targets, however, Roche’s RG7888 and Amgen’s AMG 820 could get the most attention. Not only has there been precious little data so far from agents acting on immune checkpoints beyond PD-1/PD-L1 and CTLA4, but investors will also note potential readacross to other assets.

For instance, AstraZeneca has a competing anti-Ox40 MAb, MEDI6469, while the anti-CSF1R mechanism of AMG 820 is relevant to Five Prime’s FPA008, which acts the same way. AMG 820 is separately in a combo trial with Keytruda, which is also being combined with Daiichi Sankyo's PLX3397, a CSF1R tyrosine kinase inhibitor.

Other novel mechanisms – including Johnson & Johnson’s anti-Vista MAb, Astra's Ataxia telangiectasia mutated (ATM) kinase inhibitor and Novartis’s anti-Tim3 MAb – will also feature at AACR, though it is not clear at present whether any clinical data will be presented.

Second chance

The 2015 AACR meeting was the venue for the first major disappointment for CAR-T therapies in solid tumours – specifically in mesothelioma with Novartis’s CART-meso (AACR – Solid tumour CAR-T foray lives up to its low-key billing, April 20, 2015).

This year provides a second chance. In addition to a special CAR-T symposium, three cell therapy sessions will be of interest to investors in Kite Pharma and Juno. The former will present an update on the potentially pivotal Zuma-1 trial of KTE-C19 and clinical data on its first engineered T-cell receptor project, targeting the Mage A3 antigen and licensed for $1.2m from the NCI last October.

Juno will have preclinical presentations, but an update from the NCI’s anti-CD22 CAR-T project will be relevant, since Juno now holds rights to this construct, having licensed it from Opus Bio as JCAR018. Particularly important will be the extent of any benefit in patients relapsing on initial CD19-directed CAR-T therapy.

For now, however, with just abstract headlines and some abstract texts unveiled, share price reactions have been muted – with one exception: Advaxis has traded up 29% over the past month on the revelation that its listeria-based therapy axalimogene filolisbac would feature in a late-breaker. The company was hit by a US clinical hold last year, though this was lifted in December.

Given how important early-stage data are becoming for oncology projects there should be plenty more scope for share price movement once the AACR gets under way.

EP Vantage will be reporting from New Orleans, where the AACR conference begins on April 16.

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

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