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CancerNetwork® sat down with Edward B. Garon, MD, at the 2021 World Conference on Lung Cancer to talk about key findings with datopotamab deruxtecan therapy in patients with non–small cell lung cancer and other ongoing trials.
Following the 2021 World Conference on Lung Cancer (WCLC), CancerNetwork® spoke with Edward B. Garon, MD, of the David Geffen School of Medicine at UCLA, about data regarding use of datopotamab deruxtecan (Dato-DXd; DS-1062) to treat non–small cell lung cancer (NSCLC) from the TROPION-PanTumor01 trial (NCT03401358). Patients with NSCLC saw positive responses, acceptable tolerability, and efficacy throughout the trial.
Trop-2 is noted to be on cancer cells disproportionately compared to normal cells, and higher levels of Trop-2 have been associated with adverse outcomes. This led to development of a Trop-2 antibody drug conjugate. That agent was tested in a dose-escalation study; what was presented [at WCLC] was data from the does-expansion [portion]. This occurred in 3 doses, with 4 mg/kg, 6 mg/kg, or 8 mg/kg. Those are the doses that were evaluated.
What was shown was that the 8 mg/kg dose was too high in terms of tolerability. Although there were 80 patients treated and the response rate exceeded 25%, [there was an] especially high level of adverse events, and particularly interstitial lung disease [ILD]. There were 3 deaths that were associated and adjudicated as being related to the drug. Outside of that level of dosing in the 4 mg/kg and 6 mg/kg cohorts, there were no fatal ILD events, but there were some lower grade events. Tolerability in general was quite good, and the efficacy was maintained with a very respectable response rate in approximately a quarter of the patients. This was a heavily previously treated population.
These data were presented at the World Conference for Lung Cancer. Subsequently at ESMO [European Society for Medical Oncology], we focused specifically on patients who had genomic alterations. The great majority of these patients had mutations in the epidermal growth factor receptor, or EGFR gene. In that population, the response rates were in the 35% range and did span [across patients with] different prior treatments. There were some responses in other genomic mutations outside of EGFR, as well.
This has led to 2 trials that are ongoing in this area, one looking at dato-DXd in patients with genomic alterations after targeted therapy and chemotherapy, that is a single-arm study [NCT04484142]. Then [there is] a randomized study in a less heavily pretreated population [called] the TROPION-LUNG01 study [NCT04656652] comparing to docetaxel in patients who had received prior frontline therapy for metastatic non–small cell lung cancer.
Garon E, Johnson M, Lisberg A, et al. TROPION-PanTumor01: Updated Results from the NSCLC cohort of the phase 1 study of datopotamab deruxtecan in solid tumors. Presented at the World Conference on Lung Cancer. September 8-14, 2021. Virtual. Abstract MA03.02