Pfizer moves pivotal assets into the front line
An anti-integrin β6 ADC and a CDK4 inhibitor shoot for bigger markets.
An anti-integrin β6 ADC and a CDK4 inhibitor shoot for bigger markets.
Sigvotatug vedotin, the Seagen-originated ADC that is the industry's only clinical-stage asset targeting integrin β6, will shortly be in two pivotal studies, after Pfizer revealed the planned start later this month of a phase 3 trial in first-line lung cancer.
This comes a year after sigvota-V entered its first pivotal study, in previously treated NSCLC, and confirms some analysts' views that the project was one of the key reasons beyond the Adcetris franchise for Pfizer's $43bn takeover of Seagen. Its advancement into the front line mirrors the pivotal progress made by a differently acting Pfizer molecule, atirmociclib, in breast cancer.
Both phase 3 starts have been revealed in entries on the clinicaltrials.gov registry. Sigvota-V especially is in focus given its prominence in the R&D plans Pfizer outlined last year, after the group completed its post-Seagen pipeline reshuffle.
The first phase 3 study, Be6A Lung-01, tests sigvota-V versus docetaxel in non-squamous NSCLC patients who have progressed after treatment with at most platinum chemo plus an anti-PD-(L)1 drug. There is no requirement for PD-L1 expression, and overall survival and confirmed ORR are co-primary endpoints.
Now Pfizer is seeking to move sigvota-V into the front-line, with the new phase 3 pitting its Keytruda combo head to head against Keytruda monotherapy, and measuring OS and PFS co-primaries. Here there is no requirement for patients to display non-squamous histology, but a PD-L1 expression level of at least 50% is mandated.
On a cross-trial basis the benchmark for Pfizer's combo to beat is median OS of 26.3 months, and median PFS of 10.3 months, in Merck & Co's Keynote-024 study of Keytruda monotherapy in PD-L1 ≥50% expressing NSCLC irrespective of histology.
Pfizer's pivotal expansion
| Project | Mechanism | Earlier phase 3 | New phase 3 |
|---|---|---|---|
| Sigvotatug vedotin | Integrin β6 ADC | 2nd/3rd-line non-sq NSCLC | 1st-line PD-L1 ≥50% NSCLC |
| Monotherapy, vs docetaxel | Keytruda combo, vs Keytruda | ||
| 600 patients | 714 patients | ||
| OS & ORR | OS & PFS | ||
| Atirmociclib | CDK4 inhibitor | 2nd-line ER+ve HER2-ve breast cancer | 1st-line ER+ve HER2-ve breast cancer |
| Faslodex combo, vs Faslodex + Afinitor + Aromasin | Femara combo, vs Femara + CDK4/6i | ||
| 500 patients | 1,020 patients | ||
| PFS | PFS |
Source: OncologyPipeline.
Pfizer is also advancing another phase 3 asset, the CDK4 inhibitor atirmociclib, into the front line. This concerns ER-positive HER2-negative breast cancer, where the molecule has been in phase 3 in a second-line setting for about a year.
The new trial, FourLight-3, is to begin next month, according to a new clinicaltrials.gov listing, and will test the CDK4 inhibitor against approved drugs that have broad activity against CDK4 as well as CDK6 (meaning Verzenio, Ibrance or Kisqali), all on top of Femara. Thus it should provide a good test of whether homing in on CDK4 specifically can avoid toxicity.
Pfizer is clearly moving fast with a possible first-to-market asset. There are only a handful of CDK4-specific inhibitors in development, including most notably BeiGene's BGB-43395 in phase 1. Last September Roche paid $850m up front for a portfolio of CDK4 inhibitors originated by the private US biotech Regor Pharmaceuticals.
284
