Dr Gutierrez on Dato-DXd Plus Rilvegostomig in Advanced/Metastatic NSCLC

"Twenty patients are continuing on treatment, and we [have seen] an ORR of 57.5%. The adverse [effects] have been tolerable, specifically looking at interstitial lung disease and corneal abnormalities."

Martin E. Gutierrez, MD, chief of thoracic oncology and director of the Experimental Therapeutics Program at Hackensack Meridian Health, discussed the design and emerging clinical implications of cohort 5 of the phase 1b TROPION-Lung04 trial (NCT04526691), which is evaluating datopotamab deruxtecan (Dato-DXd) in combination with rilvegostomig in the first-line treatment of patients with advanced or metastatic non–small cell lung cancer (NSCLC).

Cohort 5 of TROPION-Lung04 enrolled 40 patients with stage IIIB/C or IV NSCLC without actionable EGFR, ALK, or ROS1 alterations. Participants were treated with the TROP2-directed antibody-drug conjugate Dato-DXd at 4 mg/kg every 3 weeks plus the PD-1/CTLA-4 bispecific checkpoint inhibitor rilvegostomig at 600 mg every 3 weeks. At the time of analysis, 20 patients remained on treatment, including 19 still receiving Dato-DXd and 20 receiving rilvegostomig.

Findigns demonstrated a confirmed objective response rate (ORR) of 57.5% (95% CI, 40.9%-73.0%), with higher activity observed in patients with non-squamous histology (n = 29; ORR, 62.1%; 95% CI, 42.3%-79.3%) compared with those with squamous histology (n = 11; ORR, 45.5%; 95% CI, 16.7%-76.6%). The disease control rate across the overall cohort was 95.0% (95% CI, 83.1%-99.4%), and the median duration of response was 5.8 months (95% CI, 4.5–not evaluable [NE]).

Gutierrez emphasized that these results suggest the potential of the Dato-DXd/rilvegostomig combination to offer a chemotherapy-free alternative to standard regimens involving cytotoxic agents and immune checkpoint blockade. Importantly, the combination appeared tolerable with manageable adverse effects (AEs). Key toxicities of interest, including interstitial lung disease and corneal AEs, were observed but did not raise new safety concerns relative to prior experience with either agent alone.

These early data build upon the rationale of combining a TROP2-directed ADC with dual immune checkpoint inhibition to enhance tumor control and minimize treatment-related toxicity, Gutierrez continued. He said that further studies are warranted to determine the durability of response and the utility of this regimen in biomarker-defined subgroups.