Sigvotatug Vedotin Does Not Significantly Improve Survival in NSCLC Trial

Sigvotatug vedotin, an investigational IB6-directed antibody drug conjugate, did not significantly improve overall survival (OS) vs docetaxel among patients with previously treated locally advanced, unresectable, or metastatic nonsquamous non–small cell lung cancer (NSCLC), according to a press release on topline findings from the phase 3 SigVie-002 trial (NCT06012435).¹

Among patients who received at least 1 prior line of therapy across the overall population, sigvotatug vedotin did not fulfill the trial’s primary end point of OS compared with docetaxel. Among those who received 1 prior line of treatment, investigators reported a stronger trend for OS and progression-free survival (PFS) with the experimental agent. Additionally, exploratory analysis findings showed no clear relationship between IB6 expression and responses.

The safety profile of sigvotatug vedotin in the phase 3 trial was comparable with prior reports of the agent. Investigators will submit detailed results from the study for presentation at a medical meeting in the future.

“It is important not to underestimate the activity of docetaxel as a comparator in this setting. Patients enrolled in this trial were heavily pretreated, with most having previously received both platinum-based chemotherapy and immunotherapy, yet docetaxel continues to provide meaningful clinical benefit,” Solange Peters, MD, PhD, chair of Medical Oncology & Thoracic Cancers Clinic at Lausanne University Hospital in Switzerland, stated in the press release.¹ “Although the study did not meet its [OS] end point, in second-line patients the data suggest a clinically meaningful survival benefit for sigvotatug vedotin over docetaxel, supporting continued scientific evaluation of sigvotatug vedotin in earlier lines in combination with immunotherapy.”

Investigators of the ongoing SigVie-002 trial are evaluating sigvotatug vedotin vs docetaxel among adult patients with previously treated locally advanced, unresectable, or metastatic NSCLC. Patients were randomly assigned to receive sigvotatug vedotin intravenously on days 1 and 15 of each 28-day cycle or intravenous docetaxel on day 1 of each cycle.

The trial’s primary end point was OS. Secondary end points included PFS per RECIST v1.1 criteria, objective response rate, duration of response, adverse effects, and global health status or quality of life.²

Patients 18 years and older with histologically or cytologically confirmed stage IIIB, IIIC, M1a, M1b, or M1c NSCLC per AJCC v8.0 guidelines and nonsquamous histology were eligible for enrollment on the trial. Other eligibility criteria included having measurable disease per RECIST v1.1 guidelines; an ECOG performance status of 0 or 1; and adequate hematologic, hepatic, and renal function at baseline.

Those with a life expectancy of less than 3 months, uncontrolled diabetes mellitus, and pre-existing peripheral neuropathy of grade 2 or higher were ineligible for study entry. Having active central nervous system lesions, including leptomeningeal metastasis, was also grounds for exclusion from the trial.

According to the press release, developers are currently assessing sigvotatug vedotin across multiple disease stages and patient populations with NSCLC and other solid tumors. An ongoing phase 3 study is assessing sigvotatug vedotin plus pembrolizumab (Keytruda) among those with frontline NSCLC and a PD-L1 tumor proportion score of at least 50%. Additionally, investigators are evaluating the agent in combination with PF’4404, a novel bispecific antibody designed to target VEGF and PD-L1, in early-stage lung cancer and other tumors that express IB6.

“The ability of sigvotatug vedotin to induce immunogenic cell death provides a strong rationale for combination approaches with immunotherapy, particularly in earlier treatment settings where immune competence is better preserved. In this context, the promising phase 1 efficacy signals observed in patients [who are treatment naive] with high PD-L1 expression warrant further evaluation and may represent a more effective clinical application of this strategy,” Peters concluded.¹

References

1. Pfizer announces topline phase 3 results for sigvotatug vedotin in previously treated metastatic non-squamous non-small cell lung cancer. News release. Pfizer. June 22, 2026. Accessed June 23, 2026. https://tinyurl.com/mrezz6vs
2. A study of SGN-B6A versus docetaxel in previously treated non-small cell lung cancer. ClinicalTrials.gov. Updated May 27, 2026. Accessed June 23, 2026. https://tinyurl.com/4ecc3nw2