Esmo 2020 preview – a kidney cancer showdown gets star billing

Though late-breakers rightfully seize much of the limelight at the Esmo congress, investors should look further afield too.

Conferences

This year’s Esmo meeting, starting in virtual format in a week, should show whether Bristol Myers Squibb and Exelixis have a chance of competing against Keytruda’s attempt to muscle in on their established territory in front-line renal cancer.

This will come courtesy of the Checkmate-9ER study, full data from which has secured star billing at a presidential session on Saturday. And, though the meeting tends to offer slim pickings for biotech investors, presentations of trials featuring novel oncology mechanisms and combinations should not be ignored either.

Only the titles are available for most abstracts at present, and the texts of poster presentations will go live at 6:05pm Eastern time on Sunday (12:05am Monday central European time). The rest of the presentations, including late-breakers, will not be made available until two embargo lifts, at 6:05pm Eastern next Thursday and Friday.

Checkmate-9ER, pitting Opdivo plus Cabometyx in front-line renal cancer, is vital as it represents Bristol and Exelixis’s bid to remain relevant in this setting. Renal cancer is thought to be Opdivo’s most important use, but combinations of Inlyta with Bavencio, and especially with Keytruda, pose a serious threat.

While Opdivo and Cabometyx were initial competitors, based on the Checkmate-214 and Cabosun trials, the space has moved on quickly, and ’9ER is a nod to the fact that checkpoint blockade plus kinase inhibition is now the dominant force in front-line disease.

9ER’s hazard ratios have been toplined, but the absolute median numbers for progression-free and overall survival, as well as patient demographics, will be a key focus at Esmo.

Selected Esmo 2020 presentations (excluding late-breakers)
Project Company Abstract Setting Study Presentation
Sotorasib Amgen 1257O NSCLC Codebreak-101* 2:25pm 20 Sep
Amivantamab + lazertinib J&J/Genmab 1258O EGFR-Met bispecific + TKI in EGFR+ NSCLC NCT04077463 2:37pm 20 Sep
Vibostolimab Merck & Co 1400P PD-(L)1-refractory NSCLC, +/- Keytruda  NCT02964013 On demand 17 Sep
Adavosertib Astrazeneca 1785P Wee1 inhibitor + Lynparza in SCLC NCT02937818 On demand 17 Sep
Opdivo + Cabometyx BMS/Exelixis/Ipsen 696O 1L renal cancer, vs Sutent Checkmate-9ER Prez symp 19 Sep
Keytruda Merck & Co 915MO 1L head & neck, monotherapy or chemo combo Keynote-048 ?
Lynparza + Imfinzi Astrazeneca 814MO Non-gBRCA ovarian, +/- Avastin Mediola ?
Imfinzi +/- tremelimumab Astrazeneca 697O 1L urothelial cancer Danube (failed) 4:32pm 19 Sep
BGB-A333 + tislelizumab Beigene 535MO Urothelial cancer, anti-PD-L1/anti-PD-1 combo NCT03379259 ?
Lucitanib Clovis ? Opdivo combo Lio-1 ?
MK-4830 Merck & Co 524O Anti-ILT4 MAb NCT03564691* 4:20pm 20 Sep
Sym021 +/- Sym022 or Sym023 Servier 1019O Anti-PD-1 +/- anti-Lag3 or anti-Tim-3 NCT03311412 2:37pm 20 Sep
Tyvyt Lilly/Innovent 991P 1L liver, IBI305 (Avastin biosimilar) combo NCT04072679 On demand 17 Sep
177Lu-satoreotide tetraxetan Ipsen 1160O Neuroendocrine tumours, SSRT2 antagonist NCT02592707 2:37pm 20 Sep
MGD019 Macrogenics 1020O PD-1 x CTLA-4 DART bispecific NCT03761017 3:09pm 20 Sep
AK104 Akeso 1021O Mesothelioma, PD-1 x CTLA-4 bispecific ? 3:21pm 20 Sep
Auto3 Autolus 890MO DOR update in DLBCL Alexander ?
ALKS 4230 Alkermes 1027MO Monotherapy + Keytruda combo Artistry-1 ?
XMT-1536 Mersana 836P Ovarian cancer, NaPi2b ADC NCT03319628* On demand 17 Sep
Source: Esmo & company announcements. Note: *assumed; presentation times in central European time.

Other studies will be of interest for competitor read-across. These include Amgen’s sotorasib, though only in NSCLC, which will be followed by Mirati shareholders and other fans of Kras targeting, and Merck & Co’s anti-Tigit MAb vibostolimab, which is of interest to investors in Arcus and in the recently floated Iteos.

Despite Roche and Merck’s massive investments in the Tigit mechanism this approach looks like only having potential as part of a PD-(L)1 combo, and – judging by Roche’s early data – mainly in PD-L1-high subjects. The opportunity for Merck and others to differentiate themselves is clear.

A somewhat under-the-radar trial, the Mediola study of Astrazeneca’s Lynparza combined with Imfinzi and Avastin in non-BRCA mutated ovarian cancer, could help investors handicap a large clinical programme testing Lynparza in combination with Keytruda, especially the Keylynk-001 trial in a similar setting.

Novel mechanisms

And, as far as novel mechanisms go, Merck’s anti-immunoglobulin-like transcript 4 project MK-4830, Alkermes’s attempt at utilising IL-2, via ALKS 4230, and Mersana’s NaPi2b antibody-drug conjugate XMT-1536 will attract attention. Mersana surged 69% in May on very early XMT-1546 data, so it has a lot to live up to.

Beyond Exelixis and Ipsen’s involvement in Checkmate-9ER biotech investors might also look to PD-1/CTLA-4 bispecific approaches from Macrogenics and Akeso, which feature in oral Esmo presentations. Servier’s low-key PD-1 asset, combined with Lag3 and Tim3 blockade, gets a similar billing.

However, perhaps the most intriguing abstract will come from Beigene, which is combining PD-1 and PD-L1 blockade in a trial of urothelial cancer patients. There has been some debate about which is the better approach, but whether they should be combined has not really been tested.

Whether this early study is capable of demonstrating an additive effect is a separate question, of course.

A 'prepping for Esmo' discussion with healthcare specialist and biotech investor Brad Loncar is free to listen to here. The Esmo 2020 congress takes place in virtual format on September 19-21.

A story on late-breaking abstracts has been published separately.

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