Dr Malhotra on the Future of Sigvotatug Vedotin in NSCLC

“We don’t have a lot of options for patients with pretreated [NSCLC]. [Options] usually [include] single-agent chemotherapy such as docetaxel or gemcitabine, which we know have many toxicities and are not [very] effective. Any trial that shows significant results in this setting will be welcomed because we need to improve outcomes for our patients.”

Jyoti Malhotra, MD, MPH, interim division chief of Thoracic Medical Oncology, associate professor in the Department of Medical Oncology & Therapeutics Research, and the director of thoracic medical oncology at City of Hope, discussed future research directions for the antibody-drug conjugate sigvotatug vedotin (SGN-B6A) in non–small cell lung cancer (NSCLC).

Sigvotatug vedotin is currently being compared with docetaxel for patients with pretreated NSCLC in the phase 3 Be6A Lung-01 trial (NCT06012435). Malhotra noted that positive data from this study would be a welcome addition to the current body of research in pretreated NSCLC, as effective options for this patient population are limited. These patients are usually treated with single-agent chemotherapy, such as docetaxel or gemcitabine, which traditionally have limited efficacy and cause adverse effects, she added.

If sigvotatug vedotin shows significant efficacy and a tolerable safety profile in this pretreated patient population, there will likely be interest in moving it into frontline therapy, Malhotra noted. Sigvotatug vedotin could also be combined with immunotherapy in the first-line setting and compared with standard-of-care therapies in future clinical trials, she added. Prior safety data with sigvotatug vedotin in combination with pembrolizumab (Keytruda) have demonstrated that the combination was well tolerated, including in treatment-naive patients, warranting further investigation, she concluded.

Findings from the phase 1 SGNB6A-001 study (NCT04389632) presented during the 2025 ASCO Annual Meeting demonstrated that efficacy-evaluable patients with treatment-naive NSCLC (n = 21) achieved an overall response rate (ORR) of 57.1% (95% CI, 34.0%-78.2%) with sigvotatug vedotin plus pembrolizumab; the complete response rate was 9.5%. The confirmed ORR was 42.9% (95% CI, 21.8%-66.0%). At a median follow-up of 4.8 months (95% CI, 3.7-6.0), the median duration of response was not reached. The disease control rate was 90.5% (95% CI, 69.6%-98.8%).