Dato-DXd Seems Safe, Efficacious in Advanced Gynecologic Cancers

Datopotamab deruxtecan(Dato-DXd) demonstrated antitumor activity in patients with advanced/metastatic ovarian or endometrial cancer who had prior chemotherapy treatment.

Datopotamab deruxtecan (Dato-DXd) was tolerable and demonstrated antitumor activity in patients with advanced/metastatic ovarian and endometrial cancer whose disease progressed after platinum chemotherapy, according to results from the phase 2 TROPION-PanTumor03 (NCT05489211) study presented at the 2024 ESMO Congress.¹

In the ovarian cancer cohort (n = 35), the confirmed objective response rate (ORR; RECIST v1.1) at a median follow-up of 14.5 months (range, 10.4-15.4) was 42.9% (95% CI, 26.3%-60.6%), comprising a complete response (CR) rate of 2.9% (n = 1) and a partial response (PR) rate of 40.0% (n = 14). The median time to response was 1.4 months (range, 1.2-8.2) and the median duration of response (DOR) was 5.7 months (95% CI, 2.9-not calculable [NC]). The disease control rate (DCR) was 85.7% (80% CI, 75.1%-92.9%). Three patients (8.6%) had progressive disease. The median progression-free survival (PFS) in this cohort was 5.6 months (95% CI, 4.1-7.0).

Among patients in the ovarian cancer cohort who were platinum sensitive (n = 9), the ORR was 66.7% (95% CI, 29.9-92.5) vs 34.6% (95% CI, 17.2-55.7) in patients who were platinum resistant (n = 26). The CR, PR, and DCR rates were 11.1% vs 0%, 55.6% vs 34.6%, and 100% vs 80.8%, respectively. The median DOR was 8.5 vs 5.6 months, respectively. There were 3 patients in the platinum-resistant group who experienced disease progression vs 0 patients in the platinum-sensitive group.

In the endometrial cancer cohort (n = 40), the confirmed ORR at a median follow-up of 13.6 months (range, 2.1-19.6) was 27.5% (95% CI, 14.6%-43.9%), comprising a CR rate of 2.5% (n = 1) and a PR rate of 25.0% (n = 10). The DCR was 57.5.% (80% CI, 46.1%-68.3%). The median time to response was 2.8 months (range, 1.4-4.2) and the median DOR was 16.4 months (95% CI, 7.1-NC). Five patients (12.5%) had progressive disease. The median PFS was 6.3 months (95% CI, 2.8-NC).

The median duration of therapy was 5.6 months (range, 1.4-14.8) vs 5.2 months (range, 0.7-19.3) in the ovarian vs endometrial cohorts, respectively. Grade 3 or higher treatment-emergent adverse events (TEAEs) and serious TEAEs occurred in 54.3% vs 57.5% and 28.6% vs 27.5% of the 2 arms, respectively. TEAEs leading to dose reduction, interruption, or discontinuation occurred in 37.1% vs 25.0%, 45.7% vs 35.0%, and 5.7% vs 7.5% of the ovarian and endometrial cohorts, respectively. There were no TEAE-related deaths in either arm.

Stomatitis and nausea, mostly grade 1 or 2, were the most common TEAEs in both cohorts. One patient in each cohort experienced grade 3 adjudicated drug-related interstitial lung disease. Also of note, ocular surface events were experienced by 40% (grade 3, 0%) of patients in the ovarian cohort and 27.5% (grade 3, 5%) of patients in the endometrial cohort; none of these events was grade 4 or 5.

“Dato-DXd monotherapy demonstrated encouraging efficacy in patients with advanced/metastatic ovarian cancer and prior platinum chemotherapy,” said presenting author Ana Oaknin, MD, head of the Gynaecological Tumour Unit and Clinical Investigator of the Gynaecological Cancer Research programme at the Vall d’Hebrón Institute of Oncology in Barcelona, Spain.

TROPION-PanTumor03 Study Background

The global, open-label, phase 2 TROPION-PanTumor03 study is exploring Dato-DXd (a TROP2-directed antibody-drug conjugate) as a single-agent and in combination regimens with various anticancer treatments across multiple tumor types. The results presented at ESMO were from the study arms focused on ovarian cancer and endometrial cancer. Patients in both arms were unselected for TROP2 expression, had progressed on at least 1 prior line of platinum chemotherapy, and had received a maximum of 2 therapy lines for advanced or metastatic disease.

The median patient age in the ovarian cancer arm was 61.0 years (range, 35-80), 60% of patients had an ECOG performance status of 0 and 40% of patients had an ECOG performance status of 1. Regarding race, 65.7% of patients were White, 22.9% were Asian, and the remainder were other/not reported. Major histology types included high-grade serous (77.1%) and clear cell (17.1%). Over two-thirds (68.6%) of patients had received 2 or more prior lines of therapy and 31.4% of patients had received 1 prior line. All patients had received prior platinum therapy, 71.4% had prior bevacizumab (Avastin)/lenvatinib (Lenvima), 51.4% had received PARP inhibitors, and 5.7% had prior immunotherapy.

In the endometrial cancer arm, the median patient age was 66.5 years (range, 48-78), 62.5% of patients had an ECOG performance status of 0 and 37.5% of patients had an ECOG performance status of 1. The majority of patients were White (45%) or Asian (40%), with the remainder being other/not reported. Major histology types included high-grade endometrioid (27.5%), high-grade serous (25.0%), low-grade endometrioid (17.5%), and clear cell (7.5%). All patients had prior platinum therapy, 20% had received bevacizumab/lenvatinib, 2.5% had prior PARP inhibitors, 22.5% had received immunotherapy, and 12.5% had received hormone therapy.

Oaknin noted that a key difference in patient characteristics between the 2 cohorts was that most patients in the ovarian cohort had 2 or more prior treatment lines, whereas most patients in the endometrial cohort only had 1 prior treatment line.

Patients in both arms received Dato-DXd at 6 mg/kg (IV) every 3 weeks. The primary study end points were investigator-assessed ORR and safety/tolerability. Secondary end points included PFS, DOR, and DCR.

Additional tumor types in which Dato-DXd is being evaluated in the TROPION-PanTumor03 study include gastric, prostate, colorectal, urothelial, and biliary tract cancers.

Reference:

Oaknin A, Ang, JE, Rha SY, et al. Datopotamab deruxtecan (Dato-DXd) in patients with endometrial (EC) or ovarian cancer (OC): Results from the phase II TROPION-PanTumor03 study. Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract 714MO.