Pfizer’s Phase 3 Lung Cancer Drug Misses Overall Survival Goal; Stronger Trend in Second‑Line Patients

Pfizer said Monday that its Phase 3 trial of sigvotatug vedotin in previously treated advanced lung cancer failed to show a statistically significant overall survival benefit over docetaxel in the overall study population, a setback for the company’s effort to position the drug as a broad monotherapy option in that setting. The company, however, pointed to a more favorable trend in a prespecified subgroup of second-line patients and said it will keep advancing the drug in earlier-line combination studies.

The drug, also known as SGN-B6A, is an investigational integrin-β6-directed antibody-drug conjugate from Pfizer’s post-Seagen oncology pipeline. In an investor news release issued June 22, Pfizer said the Phase 3 SigVie-002 study, previously called Be6A Lung-01 and registered as NCT06012435, enrolled 703 adults with locally advanced, unresectable or metastatic non-squamous non-small-cell lung cancer whose disease had been treated with one or more prior lines of therapy. Patients were randomized to receive sigvotatug vedotin or docetaxel, a standard chemotherapy used in previously treated NSCLC.

The trial’s primary endpoint was overall survival, a measure of how long patients live after treatment begins. Pfizer said sigvotatug vedotin did not demonstrate a statistically significant improvement in overall survival compared with docetaxel in the overall study population. The company said the drug’s safety profile was manageable and consistent with prior studies.

Pfizer also said a prespecified subgroup of patients who had received only one prior line of systemic therapy, representing about two-thirds of the study population, showed a stronger trend favoring sigvotatug vedotin for both overall survival and progression-free survival, which measures how long a patient lives without the disease worsening. But the company did not release key efficacy details, including hazard ratios, p-values, median overall survival, median progression-free survival, response rates, duration of response or detailed safety tables. Pfizer also said an exploratory analysis did not observe a clear IB6 expression-response relationship.

“Patients with previously treated advanced NSCLC are a historically difficult-to-treat population, and there is clearly more work to be done to improve the outcomes for this population,” said Jeff Legos, Pfizer’s chief oncology officer.

Missing an overall survival endpoint is a meaningful blow in a late-stage cancer study, particularly in previously treated metastatic NSCLC, where survival remains a central benchmark for judging whether a new therapy improves outcomes. Docetaxel remains an established treatment option in this setting, which is why it was used as the control arm.

The result is also notable for Pfizer’s broader cancer strategy. Sigvotatug vedotin came from Seagen, the antibody-drug conjugate specialist Pfizer acquired on Dec. 14, 2023, to bolster its oncology portfolio. Despite the SigVie-002 miss, Pfizer said it remains confident in the program’s potential in earlier-line use and is continuing another Phase 3 study, SigVie-003, which is testing sigvotatug vedotin plus pembrolizumab as a first-line treatment for advanced NSCLC in patients with PD-L1 tumor proportion score of at least 50%.

“Although the overall study results did not demonstrate superiority over docetaxel, it is encouraging that second-line patients treated with sigvotatug vedotin achieved strong efficacy outcomes compared to an established standard of care, alongside a manageable safety profile,” Legos said.

Pfizer said detailed results from SigVie-002 will be submitted for presentation at a future medical congress.