Boehringer beats Bayer to the regulators
The FDA will rule on a low dose of zongertinib in the summer.
The FDA will rule on a low dose of zongertinib in the summer.
In the all-German battle to get a targeted small molecule approved for second-line HER2-mutated non-small cell lung cancer, Boehringer just moved ahead of its rival Bayer. The former announced on Wednesday that the FDA had accepted its contender zongertinib with priority review.
Bayer’s plans for its hopeful, BAY2927088, are still unclear. However, a closer look at the data shows that Boehringer has had to file the lower zongertinib dose tested, 120mg daily, presumably because of toxicity. Bayer, meanwhile, has so far focused on a 20mg twice-daily dose that has been linked with a higher rate of dose reductions and discontinuations – and one death – which might help explain any hesitancy in its filing plans.
Still, liver enzyme elevations could be a problem for zongertinib. These became apparent at last year’s World Lung meeting, when Boehringer presented data on 120mg and 240mg doses. The company reported updated results with the 120mg dose in December at ESMO Asia, but this still found a 21% rate of AST elevation, including 5% at grade 3 or above.
Cross-trial comparison of zongertinib & BAY2927088 in HER2m NSCLC
Zongertinib | BAY2927088 | |
|---|---|---|
| Company | Boehringer Ingelheim | Bayer |
| Regulatory status | PFUDA date “Q3 2025” (assumed Aug) | Unknown |
| Trial | Beamion Lung-1 cohort 1 (2nd-line) | Soho-01 cohort D (2nd-line) |
| ORR | 71% (53/75)* | 72% (31/43) |
| AST elevations | 21% (5% at ≥gr3)* | 14% (2% at ≥gr3) |
| AEs leading to dose reductions | 5%* | 32% |
| AEs leading to discontinuations | 3%* | 7% |
| Fatal TRAEs | 0%* | 2% |
| Confirmatory trial | Beamion Lung-2 (1st-line) | Soho-02 (1st-line) |
Note: *for 120mg daily dose only (240mg daily was also tested). Source: OncologyPipeline.
One question, therefore, is whether the FDA will convene at adcom to discuss zongertinib, which is due a decision in the third quarter, according to Boehringer.
At least efficacy doesn’t seem to be in doubt: the latest numbers give an ORR of 71% with 120mg, while the 240mg dose didn’t add much more, giving an ORR of 78%.
Boehringer and Bayer have already started phase 3 trials, presumably designed to confirm any approvals, which look likely to be on an accelerated basis. Both studies are enrolling first-line HER2-mutated NSCLC patients, so could also expand the addressable populations for both projects.
Boehringer’s Beamion Lung-2 has a primary completion date in November 2025, while Bayer’s Soho-02 is set to finish in April 2027, according to clinicaltrials.gov.
Boehringer says that HER2 mutations occur in 2-4% of NSCLC patients, and this niche seems to be the focus for now, despite previous claims of activity with zongertinib in HER2 wild-type NSCLC. Bayer’s next move will be eagerly awaited.
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