AACR preview: a lung cancer showdown

Any remaining notion that the AACR meeting is a venue for niche, early-stage research just went out of the window. Abstract titles unveiled yesterday have confirmed that this year’s instalment will see a first-line lung cancer showdown, with pivotal trial results pitting the three leading anti-PD-(L)1 players against each other.

It is just as well that the meeting will be held at the huge McCormick Place centre in Chicago – better known as the established venue for Asco. Investors should brace themselves for a packed turnout at the “immunotherapy combinations: the new frontier in lung cancer” session on April 16 (see table below).

The pivotal data presentations at this session will feature Merck & Co’s Keynote-189, Bristol-Myers Squibb’s Checkmate-227 and Roche’s Impower-150 trials. Of course, all three have already generated topline results that the respective companies have touted as positive, but delegates will be looking for additional information to determine just how accurate such upbeat assessments are.

It cannot be denied that Merck’s Keytruda already has a stranglehold on first-line NSCLC by virtue of its accelerated approval and the unexpectedly early positive readout of Keynote-189, which combined it with chemo. For its part, in Impower-150 Roche is trying to allay doubts about whether Avastin adds anything to the Tecentriq plus chemo combo (All to play for in first-line lung cancer, Roche insists, February 2, 2018).

Most of the AACR presentations are still embargoed apart from the abstract titles, and it seems that the Impower-150 analysis will focus on PD-L1 expression subgroups. 

Tumour mutation burden?

Perhaps the most eagerly awaited is a full readout from Bristol’s Checkmate-227, a study in which the company had controversially claimed a win by pivoting at the eleventh hour to cut the data by patients’ tumour mutation burden.

Investors will want reassurance that this is a clinically and statistically relevant subgroup analysis, and will also look to another Opdivo/Yervoy first-line NSCLC study, Checkmate-568. This had at one time – after the blow-up of Checkmate-026 – been suggested as a registrational trial, but after Checkmate-568 had been upsized this plan was dropped and the trial was de-emphasised.

Now it has gained fresh relevance, with Bristol at AACR touting it as providing supporting evidence for the tumour mutation burden cut-off it had used in Checkmate-227. Expect tumour mutation burden to be one of the key themes of AACR.

Selected AACR 2018 presentations
Project Company Detail Trial ID Abstract
Keytruda + chemo Merck & Co Phase III 1st-line NSCLC (Keynote-189) NCT02578680 CT075
Tecentriq + Avastin + chemo Roche 1st-line NSCLC (Impower-150) NCT02366143 CT076
Opdivo + Yervoy Bristol-Myers Squibb 1st-line NSCLC (Checkmate-227) NCT02477826 CT077
Opdivo + Yervoy + chemo Bristol-Myers Squibb TMB cutoff identification in 1st-line NSCLC (Checkmate-568) NCT02659059 CT078
Imfinzi + tremelimumab Astrazeneca Urothelial bladder cancer data (unclear) CT112
Bavencio Pfizer/Merck KGaA Gastric cancer (Javelin Solid Tumor study) NCT01772004 CT111
BLU-667 Blueprint Medicines Phase I in Ret-altered tumours NCT03037385 CT043
Lorlatinib Pfizer Alk-positive NSCLC NCT01970865 CT044
CDX-301 Celldex FLT3 ligand in NSCLC NCT02839265 CT005
Taselisib Roche Basket study in PI3kCA-mutated tumours NCT01296555 CT046
Miransertib  Arqule Phase I in PI3kCA or Akt1-mutant ovarian cancer NCT02476955 CT035
CMP-001/CYT003 + Keytruda Checkmate Pharmaceuticals TLR9 agonism in PD-1 inhibitor resistant melanoma NCT03084640 CT144
1RG-CART Cancer Research UK Anti-GD2 CAR-T  in neuroblastoma NCT02761915 CT145
ALT-803 Altor Bioscience First-in-human combo with anti-CD20 MAb NCT02384954 CT146
TSR-042 Tesaro Phase I safety & efficacy of anti-PD-1 MAb (Garnet study) NCT02715284 CT053/6
CYC065  Cyclacel Phase I safey & pharmacokinetics NCT02552953 CT037
General CAR-T therapy (none) Prior chemo might impair effective CAR-T cell manufacture 1631/3
Magsense Imagion Biosystems Detecting Her2-positive cells LB-060/1
SRA737  Sierra Oncology/Sareum Parp inhibitor-resistant & CCNE1-amplified ovarian cancer LB-265/9
Humalutin/177Lu-NNV003 Nordic Nanovector Preclinical evaluation 848/11
Bemcentinib/BGB324 Bergenbio Axl kinase preclinical data 3774/24
INCB081776 Incyte Characterisation of Axl/Mer kinase inhibitor 3759/9
AsiDNA Onxeo DNA break repair inhibitor + HDAC inhibitor 2818/8
ADU-1604 Aduro Biotech Preclinical evaluation of anti-CTLA4 MAb 1702/27

There will also be presentations of trials in second-line NSCLC, including one involving Astrazeneca’s Imfinzi plus tremelimumab. However, Keytruda seizing the first-line market has left very little opportunity for checkpoint blockade in later lines of lung cancer therapy – at least in the US.

As such, those interested in the continued march of anti-PD-(L)1 therapy will take more interest in other indications, including, for instance, Bavencio in gastric cancer. And followers of a key 2018 theme in this space – how to make PD-L1-negative tumours respond to checkpoint blockade – will note sessions including those focusing on Altor’s ALT-803 and Checkmate Pharmaceuticals’ CYT003.

Other early-stage approaches will also fight for attention, but this year the spotlight on first-line lung cancer will prove hard to shift.

The AACR meeting this year takes place in Chicago, and begins on April 14.

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

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