Datopotamab (Dato-Dxd) Treatment for Non-Small Cell Lung Cancer
Recently published study results suggest Datopotamab deruxtecan (Dato-DXd; DS-1062a), a TROP2-directed antibody drug conjugate (ADC) appears effective in treating certain patients with advanced, or metastatic, non-small cell lung cancer (NSCLC). When used as a second line treatment it was found to delay cancer recurrence when compared with standard-of-care Taxotere (docetaxel) in patients with locally advanced or metastatic NSCLC.2,3,9
About Datopotamab Deruxtecan
Datopotamab deruxtecan is a precision cancer medicine known as an antibody drug conjugate (ADC). The anti-TROP2 (trophoblast cell-surface antigen 2) monoclonal antibody delivers a topoisomerase I inhibitor cytotoxic chemotherapy (“payload”) directly to cancer cells via a linker attached to the monoclonal antibody that binds to TROP2 on the cancer cells. TROP2 is a transmembrane glycoprotein that is over expressed in many cancers and is associated with poor overall and disease-free survival. TROP2 expression has been observed in up to 64% and 75% of adeno and squamous cell NSCLC's respectively.4-7 There are no TROP2-directed therapies or ADCs currently approved for the treatment of NSCLC.
Cancer Connect Lung Cancer Newsletter
About the TROPION-PanTumor01 Clinical Trial
The TROPION-PanTumor01 clinical trial was designed to evaluate the safety, tolerability, and preliminary effectiveness of Dato-Dxd in patients with advanced solid tumors that were refractory to or relapsed from standard treatment or for whom no standard treatment was available. In the trial, objective response rates ranging from 21% to 25%, including complete response's, were observed in the 159 patients with advanced, or metastatic NSCLC receiving different doses of Dato-DXd. In a sub-group analysis released at ESMO 2020 researchers reported that advanced NSCLC patients with various actionable genomic alterations also responded to Dato-DXd. Of the 34 evaluable NSCLC patients with actionable genomic alterations the objective response rate was 35%. At a median follow-up of 13.4 months, the median duration of response was 9.5 months. Patients with EGFR exon19 deletions and L858R mutations responded to Dato-DXd even after treatment with Tagrisso.
TROPION-Lung01 Clinical Trial Results
The TROPION-Lung01 trial was designed to confirm the activity of Dato-DXd by comparing it to standard treatment with Taxotere. Dato-DXd was reported to delay the time to cancer recurrence in patients with metastatic non-squamous NSCLC. Individuals with squamous cell histology did not experience any benefit according to data released at the October 2023 ESMO Annual Congress in Madrid.
Thirty-one percent of patients with non-squamous NSCLC responded to treatment with Dato-DXd compared with 13% off those treated with Taxotere and survived without cancer progression an average of 5.6 months compared with 3.7 months. The median duration of response was 7.7 months compared to 5.6 months, for Taxotere and Dato-DXd treated patients respectively which translated to a median survival duration of 12.4 months compared with 11.0 months for Taxotere.
Cancer Connect Lung Cancer Newsletter
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Dato-DXd Side Effects
The most commonly reported side effects are mucositis, fatigue, and anemia. Fourteen individuals (8%) developed a lung toxicity called interstitial lung disease (ILD) in the early trials, resulting in fatality in three patients. The majority of ILD cases (12/14) and the three deaths were reported at the highest dose evaluated. In the TROPION-Lung01 trial dry eye occurred in 6% and drug related ILD resulted in 3 deaths according to the treating physicians. The researchers concluded that
Dato-DXd Drug Combinations
The combination of Dato-DXd with the checkpoint inhibitor immunotherapy drug Imfinzi, with or without carboplatin chemotherapy appeared effective and safe in patients with advanced NSCLC according to an interim analysis of the TROPION-Lung04 clinical trial presented at the 2023 World Conference on Lung Cancer. The overall response rates were 50% for Dato-DXd and Imfinzi, and 77% for Dato-DXd combined with Imfinzi and carboplatin. Interstitial lung disease was experienced by 15.8% and 7.1% respectively and there were no fatalities from ILD.8
According to the TROPION-Lung01 investigators “Dato-DXd is the first antibody drug conjugate to demonstrate a significant improvement over Taxotere in patients with previously treated locally advanced or metastatic NSCLC, ILD was observed and highlights the need for careful monitoring and adherence to ILD management guidelines.”
Dato-DXd is currently being evaluated in several phase 3 trials, including AVANZAR (NCT05687266), TROPION-Lung07 (NCT05555732) and TROPION-Lung08 (NCT05215340) trials. These studies will investigate Dato-DXd as first-line treatment in patients with advanced or metastatic NSCLC combined with immune checkpoint inhibitors. Dato-DXd must go through the FDA approval process before it can become available. If approved, an additional advantage is that an additional biopsy of the lung cancer will not be required to begin therapy
Connect With Others for Support and information
Cancer Connect was the first social network created for people with lung cancer. Founded by oncologists to support cancer patients and their caregivers, over 40 million individuals have accessed Cancer Connect programs since 1997. Cancer Connect is used by leading cancer centers like Dana Farber, Roswell Park and The James at Ohio State to support their patients. Join the conversation, ask questions, share your experience, and learn how the best cancer centers are treating lung cancer from others. Share your experience, ask a question, or start a conversation by posting on Cancer Connect.
References
- Clinicaltrials.gov. DS-8201a in human epidermal growth factor receptor 2 (HER2)-expressing or -mutated non-small cell lung cancer (DESTINY-Lung01). Available here. Accessed January 2021.
- Datopotamab deruxtecan met dual primary endpoint of progression-free survival in patients with advanced non small cell lung cancer in TROPION-Lung01 phase 3 trial. News release. Daiichi Sankyo. July 3, 2023. Accessed July 5, 2023. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202307/20230703_E.pdf
- Study of DS-1062a versus docetaxel in previously treated advanced or metastatic non-small cell lung cancer with or without actionable genomic alterations (TROPION-LUNG01). ClinicalTrials.gov. Updated July 4, 2023. Accessed July 5, 2023. https://clinicaltrials.gov/study/NCT04656652
- Inamura K, et al. Association of tumor TROP2 expression with prognosis varies among lung cancer subtypes. Oncotarget. 2017;8(17):28725-28735.
- Pak M, et al. Significance of EpCAM and TROP2 expression in non-small cell lung cancer. World J Surg Oncol. 2012;10:53.
- Li Z, et al. TROP2 overexpression promotes proliferation and invasion of lung adenocarcinoma cells. Biochem Biophys Res Commun. 2016;470:197-204.
- Liu T, et al. Overexpression of TROP2 predicts poor prognosis of patients with cervical cancer and promotes the proliferation and invasion of cervical cancer cells by regulating ERK signaling pathway. PLoS One. 2013;8:e75864
- Papadopoulos KP, Bruno DS, Kitazono S, et al. Datopotamab deruxtecan (Dato-DXd) + durvalumab ± carboplatin in advanced/mNSCLC: Initial results from phase 1b TROPION-Lung04. Presented at: 2023 World Conference on Lung Cancer; September 10-12, 2023; Singapore. Abstract OA05.06.
- Ahn MJ, Lisberg A, Paz-Ares L, et al. Datopotamab deruxtecan (Dato-DXd) vs docetaxel in previously treated advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC): results of the randomized phase 3 study TROPION-Lung01. Ann Oncol. 2023;34(suppl 2):S1305-S1306. doi:10.1016/j.annonc.2023.10.061
