SITC 2020 – second chances for Merck & Co and Oncosec

Among late-breaking abstracts whose titles have just gone live two mechanisms have a chance to redeem themselves.

Conferences

When the Society of the Immunotherapy of Cancer meeting gets under way next week, in virtual format, of course, it could provide an opportunity to show that Rig1 activation and the delivery of plasmid-based IL-12 are, after all, viable oncology approaches.

Both MK-4621, a Rig1 agonist Merck & Co got through its $115m takeover of Rigontec, and Tavo, Oncosec’s electroporation-delivered IL-12 gene therapy, have disappointed, but they feature among a handful of the meeting’s clinical late-breaking presentations, whose titles have just been announced. Intriguingly, a second Rig1 asset, Curevac’s CV8102, is also among the late-breakers.

CV8102 is an RNA therapeutic that additionally activates TLR7/8, and featured at this year’s Asco conference, showing an underwhelming 9% remission rate as monotherapy in cutaneous melanoma. Of the two patients who responded one was PD-L1 naive, while the other was checkpoint refractory.

The SITC late-breaker should detail its combination with PD-1 blockade, and might involve other cancer types too. CV8102 and MK-4621 are the only Rig1 activators in clinical trials for cancer, according to EvaluatePharma; Spring Bank’s inarigivir is in phase II for hepatitis B.

In an earlier study, presented at Esmo 2018, Merck’s MK-4621 also disappointed, though in fairness it might have been too early for it to have yielded meaningful efficacy data. Like for the already announced SITC abstracts, the contents of the late-breakers will not be unveiled formally until just before the meeting (SITC 2020 – embargo snafu triggers the first movers, October 15, 2020).

Selected late-breaking studies at SITC 2020
Project Mechanism Company Detail
MK-4621 Rig1 activator Merck & Co Safety and efficacy results from Keytruda combo in solid tumours
CV8102 TLR & Rig1 agonist (ssRNA) Curevac Ph1 +/- anti-PD-1 antibodies in solid tumours
mRNA-4157 Personalised cancer vaccine Moderna Keynote-603, Keytruda combo
Tavo Plasmid-based IL-12 gene therapy Oncosec Keynote-695, Keytruda combo in anti-PD-1 refractory melanoma
SO-C101 IL-15 superagonist Sotio Ph1 +/- Keytruda in solid tumours; private Czech company
ENB003 Deuterated endothelin B receptor antagonist ENB Therapeutics Ph1/2 Keytruda combo in solid tumours
Penpulimab (AK105) Anti-PD-1 MAb Akeso/Sino ≥3L nasopharyngeal carcinoma; filed in China for classical Hodgkin's lymphoma
Urelumab Anti-CD137 MAb Bristol Myers Squibb Combo with vaccine + Opdivo as neoadjuvant and adjuvant for pancreatic cancer
MCLA-145 Anti-CD137xPD-L1 bispecific Merus/Incyte Likely preclinical; 2016 deal
FPA157 Anti-CCR8 MAb Five Prime First preclinical data
DT095895 EP4 receptor antagonist Domain Therapeutics Preclinical
Source: SITC & clinicaltrials.gov.

The Keynote-695 study of Oncosec’s Tavo, meanwhile, looks specifically at checkpoint-refractory melanoma, but has already disappointed not once but twice.

Oncosec, in common with numerous oncology combo players, is hoping to turn “cold” tumours immunogenic and thus make them amenable to checkpoint blockade. The group calls Keynote-695 a registration-enabled phase IIb study, but despite promise in an early trial it looks like time is running out for Tavo.

Another company aiming to overcome tumour resistance is ENB Therapeutics, and it too is looking at a Keytruda combo.

Among other SITC late-breakers, presentations on Bristol Myers Squibb’s urelumab and Merus/Incyte’s MCLA-145 will be of interest to those following the anti-CD137 approach, where Pfizer’s utomilumab has extensively been studied in various combinations. Little has been disclosed about MCLA-145, the subject of a 2016 tie-up, and its SITC presentation is likely preclinical.

The first preclinical data will also be revealed on Five Prime’s FPA157, which the company says is engineered to eliminate tumour-infiltrating T regulatory cells. Tregs are one mechanism behind tumour resistance, and have attracted deal-making, most recently between Gilead and Jounce over JTX-1811; like FPA157 this is an antibody against CCR8.

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