Positive results from the pivotal TROPION-Lung01 Phase III trial showed that datopotamab deruxtecan (Dato-DXd) demonstrated a statistically significant improvement for the primary endpoint of progression-free survival (PFS) compared to docetaxel, the current standard of care, in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) treated with at least one prior line of therapy.
These data will be shared today in the second of two late-breaking presentations for datopotamab deruxtecan in a Presidential Symposium at the European Society for Medical Oncology (ESMO) 2023 Congress in Madrid, Spain (LBA12).
Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.
Datopotamab deruxtecan reduced the risk of disease progression or death by 25% compared to docetaxel (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.62-0.91; p=0.004) as assessed by blinded independent central review (BICR). Median PFS was 4.4 months in patients treated with datopotamab deruxtecan versus 3.7 with docetaxel. Results also showed a confirmed objective response rate (ORR) of 26.4% in patients treated with datopotamab deruxtecan compared to an ORR of 12.8% with docetaxel.
In patients with non-squamous NSCLC, datopotamab deruxtecan demonstrated a clinically meaningful benefit, reducing the risk of disease progression or death by 37% compared to docetaxel (HR 0.63; 95% CI 0.51-0.78) as assessed by BICR. Median PFS was 5.6 months in patients treated with datopotamab deruxtecan versus 3.7 with docetaxel. A confirmed ORR of 31.2% was observed with datopotamab deruxtecan, including four complete responses (CRs), versus 12.8% with docetaxel which elicited no CRs. Datopotamab deruxtecan did not demonstrate a PFS benefit in patients with squamous NSCLC.
For the dual primary endpoint of overall survival (OS), interim results numerically favoured datopotamab deruxtecan over docetaxel in the overall population (HR 0.90; 95% CI 0.72-1.13) and in patients with non-squamous tumours (HR 0.77 95% CI: 0.59-1.01), however, results did not reach statistical significance at the time of this data cut-off. The trial is ongoing and OS will be assessed at a final analysis.
Aaron Lisberg, MD, UCLA Health, Thoracic Medical Oncology and investigator in the trial, said: "For patients with advanced non-small cell lung cancer, current standard of care second-line docetaxel is associated with limited benefit and substantial toxicity. The improvement in progression-free survival observed with datopotamab deruxtecan, particularly in patients with non-squamous tumours, and the improved tolerability of this antibody drug conjugate compared to docetaxel, represent a meaningful advance for patients with lung cancer."
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "Datopotamab deruxtecan is central to the future we envision where antibody drug conjugates improve upon and ultimately displace entrenched standards of care, like chemotherapy, in multiple cancer types. The TROPION-Lung01 results demonstrate for the first time that an antibody drug conjugate can delay disease progression or death for longer than conventional chemotherapy in patients with advanced non-small cell lung cancer. This is particularly noteworthy considering datopotamab deruxtecan was also associated with a lower burden of treatment-related severe adverse events than chemotherapy."
Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said, "These results shown at ESMO from the second of two pivotal trials of datopotamab deruxtecan provide further support for the practice-changing potential of our DXd antibody drug conjugate technology across different targets and types of cancer. The benefit seen in patients with non-squamous tumours is particularly impressive and, coupled with the data from TROPION-Lung05, provides promising evidence that datopotamab deruxtecan may play an important role in treating patients with non-small cell lung cancer who currently have limited effective options following initial treatment."
In the TROPION-Lung01 trial, no new safety concerns were identified with datopotamab deruxtecan. The median treatment duration for datopotamab deruxtecan was 4.2 versus 2.8 months for docetaxel. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 25% and 41% of patients in the datopotamab deruxtecan and docetaxel arms, respectively. The most common Grade 3 or higher TRAEs were neutropenia (1%, 23%), stomatitis (6%, 1%), anaemia (4%, 4%), asthenia (3%, 2%), nausea (2%, 1%) and fatigue (1%, 2%).
Grade 3 or higher adjudicated drug-related interstitial lung disease (ILD) events occurred in 3% and 1% of patients in the datopotamab deruxtecan and docetaxel arms, respectively. In the datopotamab deruxtecan arm, there were seven Grade 5 ILD events (2%) adjudicated as drug-related by an independent committee. The primary cause of death in four of these cases was attributed to disease progression by the treating investigator. Of the seven adjudicated Grade 5 ILD events, four (1.7%) were in patients with non-squamous NSCLC and three (4.6%) were in patients with squamous NSCLC. In the docetaxel arm, one adjudicated drug-related Grade 5 ILD event (0.3%) occurred.
Patient enrollment by tumour histology was consistent across treatment arms and with real world incidence with 78% and 77% of patients in the datopotamab deruxtecan and docetaxel arms, respectively, having non-squamous tumours.1 In both arms, 17% of patients had tumours expressing actionable genomic alterations, such as epidermal growth factor receptor (EGFR) mutations. At the 29 March 2023 data cut-off, 52 patients remained on treatment with datopotamab deruxtecan and 17 remained on docetaxel.
Summary of TROPION-Lung01 Efficacy Results
