Datopotamab Deruxtecan Combinations Showed Encouraging TumorResponses in Patients with Advanced Non-Small Cell Lung Cancer inTROPION-Lung02 Phase 1b trial

Datopotamab Deruxtecan Combinations Showed Encouraging Tumor
Responses in Patients with Advanced Non-Small Cell Lung Cancer in
TROPION-Lung02 Phase 1b trial

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).
Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC)
being jointly developed by Daiichi Sankyo (TSE: 4568) and AstraZeneca (LSE/STO/Nasdaq: AZN).
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 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.
“We continue to be encouraged by the findings from TROPION-Lung02, the first trial to evaluate the
combination of a TROP2 directed antibody drug conjugate and an immune checkpoint inhibitor with or
without platinum chemotherapy in patients with advanced non-small cell lung cancer,” said Mark Rutstein,
MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. “These data, alongside previous results
for datopotamab deruxtecan combined with an immune checkpoint inhibitor, reinforce the potential of these
combinations to improve outcomes for patients with different advanced cancers.”
“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
optionsfor patients with advanced lung cancer across tumor histologies and PD-L1 expression levels.

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