Esmo 2019 preview – immunotherapies grab the rest of the late-breaker focus

Away from the main small-molecule focus of this year’s Esmo meeting, Keytruda flies the flag for immuno-oncology, including in a little-noticed mesothelioma study.

Full readout of data from two recently toplined studies looks set to be the highlight for immunotherapies at this month’s Esmo meeting. Keytruda’s Keynote-522 trial in triple-negative breast cancer and Tecentriq’s Imvigor-130 test in bladder cancer were both said to be positive, and both have secured late-breaker slots.

It is noteworthy that two failed clinical trials, Keynote-119 and Checkmate-459, also feature in late-breakers, presumably as Esmo continues trying to counter excessively positive reporting of clinical data. And a low-profile mesothelioma trial threatens to steal the limelight from them all.

The details of presentations are still under wraps, Esmo having released only the titles of abstracts at this point. But given mesothelioma’s intractable nature, the co-operative group-run Promise-Meso trial of Keytruda, featured in the press programme as well as in a late-breaker, should generate interest.

Keynote-522, meanwhile, gives Merck & Co a shot at a neoadjuvant triple-negative breast cancer label, with Keytruda having been said to beat chemo alone in terms of pathological complete response; a second co-primary measure, event-free survival, has yet to read out. The failed Keytruda trial being highlighted at Esmo is Keynote-119, in relapsed breast cancer.

Followers of Roche’s Tecentriq in urothelial bladder cancer, where it has accelerated approval, will take interest in a late-breaker featuring the first-line Imvigor-130 trial, which has hit on progression-free survival. Given the US FDA’s attempts to limit prescribing Tecentriq in bladder cancer, and the failure of the second-line Imvigor-211 trial, full data are crucial to gauging Tecentriq’s opportunity here.

Also in urothelial cancer, but in the second-line setting, Immunogenics’ Trophy-U-01 study of sacituzumab govitecan has a late-breaker slot. No data from this trial appear to have been disclosed previously.

Selected Esmo 2019 presentations featuring immuno-oncology and biologicals
Study Project Company Setting Note Abstract
Friday, 27 September
Checkmate-459 Opdivo Bristol-Myers Squibb 1L hepatocellular Failed in Jun 2019 LBA38*
Keynote-021, 189, 407, 010, 042 Keytruda Merck & Co Various TMB analyses NB TMB analyses of KN-021 & 189 @ World Lung LBA79 & LBA80
Saturday, 28 September
Trophy-U-01 Sacituzumab Immunomedics 2L urothelial Not previously revealed LBA55
Keynote-119 Keytruda Merck & Co 2/3L breast Failed in May 2019 LBA21 
Checkmate-227 part 1 Opdivo + Yervoy Bristol-Myers Squibb 1L NSCLC Inconclusive trial LBA4*
NCT02892123 ZW25  Zymeworks Her2-expressing solid tumours Bispecific MAb 453PD 
Outreach  MTL-CEBPA Mina saRNAproject vs liver cancer Small activating RNA therapeutic 455PD
Sunday, 29 September
Keynote-522 Keytruda Merck & Co TNBC Positive for pCR Jul 2019 LBA8*
B-F1rst Tecentriq Roche Prospective TMB evaluation in NSCLC Initial data at Esmo 2018 LBA83
NCT02977195 NP137 Netris Pharma First-in-human solid tumour trial Anti-netrin-1 MAb 439O
Monday, 30 September
Promise-meso Keytruda Merck & Co Mesothelioma vs chemo Co-operative group trial LBA91*
Imvigor-130 Tecentriq Roche 1L urothelial Toplined positive Aug 2019 LBA14*
Note: *studies also being highlighted in Esmo's press programme.

Meanwhile, Bristol-Myers Squibb’s Checkmate-459 trial, testing Opdivo in first-line hepatocellular cancer, will be scrutinised fully, having failed in June.

Bristol will separately attempt to play up full data from part 1 of its first-line NSCLC trial Checkmate-227, though this trial now has marginal relevance. True, Bristol has heralded one Checkmate-227 analysis as positive, but for Opdivo/Yervoy the boat has likely sailed in this setting.

No doubt tumour mutation burden (TMB) will remain part of the discussion, even if it is becoming clear that much more needs to be shown before declaring this a viable biomarker. Other TMB analyses presented at Esmo include those of various Keytruda studies. Two Keytruda presentations at World Lung this week found no correlation with efficacy, and it will be interesting to hear whether B-F1rst, a Tecentriq trial designed prospectively to look at TMB in NSCLC subjects, comes to a different conclusion.

This should all provide plenty of focus for investors following biologicals and immunotherapies, though it cannot be denied that Esmo’s most stock-moving studies feature small molecules (Esmo 2019 preview – Parps on parade, September 5, 2019).

For live updates from the meeting, in Barcelona between September 27 and October 1, follow @ByAmyBrown and @JacobPlieth on Twitter.

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