The month ahead: October’s upcoming events

Spooky season is beginning, but companies presenting at upcoming conferences including ESMO and the Triple Meeting will be hoping not to get any scares. A big ESMO loser has already emerged in the shape of IO Biotech – but that group’s crash in valuation this week was linked with its inability to file its sole clinical asset Cylembio with the FDA, despite bagging an ESMO late-breaker.

Elsewhere, FDA approval decisions approach for Jazz’s Zepzelca plus Roche's Tecentriq, GSK’s Blenrep, Syndax’s Revuforj and Regeneron’s Libtayo. And earnings season is set to kick off again, led by Johnson & Johnson.

ESMO

The big draws at ESMO this year look set to be Amgen and Zai Lab’s anti-FGFR2b monoclonal antibody bemarituzumab, and various early-line Enhertu trials. Astra and Daiichi’s HER2 ADC had already been set to feature via the neoadjuvant Destiny-Breast11, but the partners revealed on Monday that the adjuvant Destiny-Breast05 would also be presented at a presidential session.

Meanwhile, Amgen and Zai originally said in June that the Fortitude-101 trial, testing a bemarituzumab/chemo combo in FGFR2b-overexpressing first-line gastric and gastroesophageal junction cancers, had succeeded, only to disclose in September that the magnitude of benefit had “attenuated”. Fortitude-101 will feature in a presidential session, so things should become clearer soon.

At ESMO, Roche will also reveal details of four failed pivotal studies of the anti-TIGIT MAb tiragolumab. 

Controversial?

As for upcoming approval decisions, a couple could be controversial. Jazz is seeking approval for a Zepzelca/Tecentriq combo as first-line maintenance in extensive-stage small-cell lung cancer. The supporting Imforte trial, presented at ASCO, showed a benefit on both PFS and OS versus Tecentriq alone, but the discussant, Dr Catherine Meador of Massachusetts General Hospital, noted that the regimen added toxicity, and said patient selection would be key.

In Imforte, two patient deaths in the combo arm were deemed related to therapy (sepsis and febrile neutropenia). Overall, there were 12 fatalities with the combo, and treatment-related grade 3/4 adverse events were seen in 26% of combo patients, versus 6% with Tecentriq alone.

GSK’s anti-BCMA ADC Blenrep has also had its share of toxicity worries, but adverse events weren't the main reason behind adcom votes against the Dreamm-7 and 8 studies designed to support use in second-line multiple myeloma. The trials tested Blenrep combos with Velcade and with Pomalyst respectively.

Instead, panellists appeared to be concerned about a low level of US enrolment, as well as a “missed opportunity” for GSK to test lower Blenrep doses.

Either way, approval looks in doubt, not helped by the FDA extending the review period by three months to review new information. Blenrep was US approved for fifth-line multiple myeloma in 2020, but that accelerated nod was rescinded when it failed the confirmatory Dreamm-3 trial.

Expansions

Other projects look more likely to receive a green light. Syndax’s menin inhibitor Revuforj, already approved for KMT2A-rearranged relapsed/refractory acute leukaemia, could add the bigger NPM1m use to its label. If Syndax succeeds here, it will have again stolen the thunder of its menin rivals Kura and Kyowa Kirin, which are awaiting an FDA decision on their contender, ziftomenib, in relapsed NPM1m disease by 30 November.

Libtayo could also get the nod in adjuvant cutaneous squamous cell carcinoma (CSCC), based on the C-Post trial, which found a 68% lower risk of disease recurrence or death with Libtayo versus placebo. Still, around 95% of CSCC patients are cured by surgery, the investigators noted, so identifying high-risk subjects, who stand to benefit most from Libtayo, could be the tricky part.

The anti-PD-1 MAb is already approved in the US for CSCC patients who aren’t candidates for curative surgery or curative radiation, as well as several other uses. Libtayo sold $1.22bn in 2024, a far cry from Keytruda’s nearly $30bn. Still, Keytruda failed to show a benefit in adjuvant CSCC, in the Keynote-630 trial. 

Investors are also still awaiting several verdicts that had been expected in previous months, including on Lilly’s Jaypirca in second-line CLL, and J&J and Genmab’s Darzalex in smouldering multiple myeloma. But the FDA last month knocked back Darzalex Faspro, in combination with Velcade, Revlimid and dexamethasone in first-line, transplant-ineligible multiple myeloma, based on the Cepheus trial. According to J&J the CRL was down to manufacturing issues.

October’s upcoming events

Source: OncologyPipeline.