TOKYO & MUNICH & BASKING RIDGE, N.J.--(BUSINESS WIRE)--Updated results from the TROPION-Lung02 phase 1b trial showed that with additional enrollment and follow-up from the initial presentation datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab with or without platinum-based chemotherapy demonstrated promising clinical activity and no new safety signals in both previously untreated or pretreated patients with advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations (AGAs). Results will be presented on June 6 during an oral presentation (#9004) at the American Society of Clinical Oncology Annual Meeting (#ASCO23). More than one million people are diagnosed with NSCLC at an advanced stage each year.1,2 While first-line treatment with immune checkpoint inhibitors with or without chemotherapy has improved outcomes for patients with NSCLC without AGAs, like EGFR or ALK, most patients eventually experience disease progression.3,4,5 TROP2 is a protein expressed in more than 90% of NSCLC tumors.6 There are currently no TROP2 directed ADCs approved for the treatment of lung cancer.7,8 Across previously untreated and pretreated patients, an objective response rate (ORR) of 38% was observed (95% confidence interval [CI]: 26-51) in patients receiving doublet datopotamab deruxtecan plus pembrolizumab (Merck & Co., Inc., Rahway, NJ, USA), an anti-PD-1 therapy. In patients receiving triplet datopotamab deruxtecan plus pembrolizumab and platinum chemotherapy, an ORR of 49% was observed (95% CI: 37-61). Disease control rates (DCR) of 84% and 87% were observed in the doublet and triplet cohorts, respectively. Median duration of response (DoR) was not reached across cohorts. Although immature, median progression-free survival (PFS) was 8.3 months (95% CI: 6.8-11.8) in the doublet cohort and 7.8 months (95% CI: 5.6-11.1) in the triplet cohort. Response rates were highest in previously untreated patients with ORRs of 50% (95% CI: 32-68) and 57% (95% CI: 42-70) observed in the doublet and triplet cohorts, respectively, with a consistent DCR of 91% observed across cohorts. “Nearly all patients with advanced non-small cell lung cancer experience disease progression following initial therapy, underscoring the need for novel therapeutic approaches across treatment lines,” said Yasushi Goto, MD, Division of Internal Medicine and Thoracic Oncology, National Cancer Center HospitalCancer Center Hospital, Tokyo, Japan. “The updated results from TROPION-Lung02 signal the potential for datopotamab deruxtecan combinations to improve outcomes for patients with non-small cell lung cancer and are a promising development in the pursuit of a new standard treatment option beyond immunotherapy.” The safety profiles of datopotamab deruxtecan-based combinations were consistent with previous data with no new safety signals observed. Grade 3 or greater treatment-related adverse events (TRAEs) occurred in 31% of patients receiving doublet therapy and 58% of patients receiving triplet therapy. The most frequent adverse events of any grade in the doublet and triplet cohorts, respectively, were stomatitis (56% and 35%), nausea (41% and 47%), anemia (21% and 48%) and fatigue (31% and 37%). Across treatment cohorts, there were 27 interstitial lung disease (ILD) or pneumonitis events adjudicated as drug-related by an independent committee. The percentage of ILD or pneumonitis events was similar across cohorts. The majority of ILD or pneumonitis events were low grade with 23 grade 1 or grade 2 and four grade 3 events. No grade 4 or grade 5 ILD or pneumonitis events or grade 5 TRAEs were observed. “With more patients and nearly a year of additional follow-up, the updated TROPION-Lung02 results show that datopotamab deruxtecan continues to elicit promising and durable responses in a diverse subset of patients with non-small cell lung cancer,” said Cristian Massacesi, MD, Chief Medical Officer and Chief Development Officer, Oncology, AstraZeneca. “These early data give us confidence in the ongoing phase 3 development program evaluating datopotamab deruxtecan combinations as potential first-line treatment options for patients with advanced lung cancer across tumor histologies and PD-L1 expression levels.” In the doublet cohort of TROPION-Lung02, 58% of patients were previously untreated and 42% were previously treated with platinum chemotherapy (38%) or immunotherapy (19%). In the triplet cohort, 75% of patients were previously untreated and 25% were previously treated with platinum chemotherapy (24%) or immunotherapy (25%). Eighty percent of patients in the doublet cohort and 73% of patients in the triplet cohort had PD-L1 tumor proportion scores of less than 50%, including 36% and 40% of patients who had PD-L1 tumor proportion scores of less than 1% in the doublet and triplet cohorts, respectively. As of the April 7, 2023 data cut-off, 36% and 46% of patients remained on the doublet and triplet therapy, respectively. Summary of Efficacy Results
ORR, %i (confirmed and pending) (95% CI)
CR, % (pending confirmation)
PR, % (pending confirmation)
Median DoR (months) (95% CI)
Median PFS (months) (95% CI)
ORR, %i (confirmed and pending) (95% CI)
CR, % (pending confirmation)
PR, % (pending confirmation)
Median DoR (months) (95% CI)
CI, confidence interval; CR, complete response; DCR, disease control rate; DoR, duration of response; NE, not estimable; ORR, objective response rate; PFS, progression-free survival; PR, partial response; SD, stable disease
iiDCR is best overall response of confirmed CR + confirmed PR + SD
The primary endpoints of TROPION-Lung02 are dose-limiting toxicities and treatment-emergent adverse events. Secondary endpoints include ORR, DoR, PFS as assessed by investigator, overall survival, pharmacokinetics and anti-drug antibodies for datopotamab deruxtecan and pembrolizumab. Most patients with NSCLC have tumors that do not express a known AGA (e.g., EGFR, ALK, ROS1, NTRK, BRAF, RET or MET).9,10,11 The current first-line standard of care for these patients is immune checkpoint inhibitors with or without platinum-based chemotherapy. Approximately 40% to 60% of tumors will not respond to this initial treatment and while these therapies may improve survival for patients whose tumors do respond, most will experience disease progression.5,7 About the DXd ADC Portfolio of Daiichi Sankyo
Designed using Daiichi Sankyo’s proprietary DXd ADC technology to target and deliver a cytotoxic payload inside cancer cells that express a specific cell surface antigen, each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. Daiichi Sankyo is dedicated to creating new modalities and innovative medicines by leveraging our world-class science and technology for our purpose “to contribute to the enrichment of quality of life around the world.” In addition to our current portfolio of medicines for cancer and cardiovascular disease, Daiichi Sankyo is primarily focused on developing novel therapies for people with cancer as well as other diseases with high unmet medical needs. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 17,000 employees around the world draw upon a rich legacy of innovation to realize our 2030 Vision to become an “Innovative Global Healthcare Company Contributing to the Sustainable Development of Society.” For more information, please visit: www.daiichisankyo.com. 1 Siegel R, et al. CA Cancer J Clin. 2021;71:7-33.
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