Daiichi Sankyo Company, Limited and AstraZeneca's datopotamab deruxtecan and ENHERTU showed encouraging results from both DXd antibody drug conjugates (ADCs) in patients with advanced or metastatic non-small cell lung cancer. Updated results from the TROPION-PanTumor01 phase 1 trial showed promising clinical activity for datopotamab deruxtecan, a TROP2 directed DXd ADC, in patients with advanced or metastatic NSCLC. Additionally, an interim analysis of the HER2 overexpressing cohort of the DESTINY-Lung01 phase 2 trial showed preliminary evidence of antitumor activity for ENHERTU, a HER2 directed ADC, in patients with metastatic NSCLC.

These data were presented in two oral presentations during the World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer (IASLC). Lung cancer is the leading cause of cancer death among both men and omen and accounts for about one-fifth of all cancer deaths globally, with 80 to 85% classified as NSCLC.1,2,3 For patients with metastatic disease, prognosis is particularly poor, as only 6 to 10% live beyond five years after diagnosis.4 Currently, there are no TROP2 directed or HER2 directed medicines approved for the treatment of NSCLC. TROPION-PanTumor01 Trial Results: In the TROPION-PanTumor01 phase 1 trial, an objective response rate (ORR) ranging from 21 to 25%, as assessed by independent central review, was observed in 159 patients with advanced or metastatic NSCLC receiving different doses of datopotamab deruxtecan (4 mg/kg, 6 mg/kg or 8 mg/kg) as of data cutoff on September 4, 2020.

Thirty-two confirmed complete or partial responses were seen, and an additional five complete or partial responses are still too early to confirm. Efficacy data were preliminary due to immaturity of follow-up across dose groups, but peliminary efficacy results may support durability of clinical activity. A disease control rate (DCR) ranging from 67 to 80% was observed with a median progression-free survival (PFS) ranging from 4.3 to 8.2 months across the three doses of datopotamab deruxtecan.

The safety profile of datopotamab deruxtecan seen in this expanded data set of TROPION-PanTumor01 phase 1 trial remains consistent with what has been previously reported. Overall, the 4 mg/kg and 6 mg/kg doses were better tolerated than the 8 mg/kg dose. The most common Grade 3 or greater treatment emergent adverse events (TEAEs) included mucosal inflammation, anemia, stomatitis and fatigue, with patients treated at the 8 mg/kg dose experiencing higher rates overall.

The most common TEAEs overall in =15% of patients included nausea, stomatitis, alopecia and fatigue. Fourteen cases (8%) of interstitial lung disease (ILD) occurred as determined by an independent adjudication committee. The majority of ILD cases (12/14) were observed with the 8mg/kg cohort, including three deaths (Grade 5).

One grade 3 ILD event was seen with the 4 mg/kg dose and one grade 2 ILD was seen with the 6 mg/kg dose. Based on the efficacy and safety findings, the 6 mg/kg dose has been identified as the recommended dose for the pivotal TROPION-Lung01 phase 3 trial. The majority of patients across all three doses were previously treated with three or more prior lines of therapy including platinum-based chemotherapy or immunotherapy (84%).

Median duration of follow-up was 7.4 months (range, 0.10-21.7). As of data cutoff on September 4, 2020, 39% of patients remained on treatment with datopotamab deruxtecan.