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, Immunomedics’ 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|
|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).