Benzinga | Dec 7, 2021 10:18AM EST

Daiichi Sankyo Reports Co. Development Program With AstraZeneca, Datopotamab Deruxtecan Continues To Show Durable Response, Disease Control In Patients with Metastatic Triple Negative Breast Cancer

* Updated data from the TNBC cohort of the TROPION-PanTumor01 phase 1 trial of Daiichi Sankyo and AstraZeneca's datopotamab deruxtecan featured as oral presentation at SABCS

TOKYO & MUNICH & BASKING RIDGE, N.J.--(BUSINESS WIRE)-- New data from the TROPION-PanTumor01 phase 1 trial of datopotamab deruxtecan (Dato-DXd), a TROP2 directed DXd antibody drug conjugate (ADC) being developed by Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and AstraZeneca (NASDAQ:AZN), continue to show encouraging durable tumor response and disease control in patients with metastatic triple negative breast cancer (TNBC) with disease progression following standard treatment. These data were featured during an oral presentation (GS1-05) at the 2021 San Antonio Breast Cancer Symposium (#SABCS21).

TNBC accounts for approximately 10 to 15% of breast cancer cases and is associated with higher disease recurrence and worse prognosis compared to other breast cancer subtypes.1,2,3 It is estimated that only 12.2% of patients with metastatic TNBC survive five years and median overall survival is generally less than two years.2,3

An objective response rate (ORR) of 34% was observed in 15 of 44 patients treated with datopotamab deruxtecan (6 mg/kg [n=42] and 8 mg/kg [n=2]) as assessed by blinded independent central review. Fourteen confirmed complete/partial responses (CR/PRs) with one additional CR/PR awaiting confirmation and stable disease in 17 additional patients were reported after a median follow-up of 7.6 months (range, 4 -- 13 months). Median duration of response (DOR) was not reached (range, 2.7 -- 7.4+ months) with the majority ongoing at the data cut-off of July 30, 2021. A disease control rate (DCR) of 77% was observed.

In a subgroup of 27 patients with measurable disease and previously untreated with a topoisomerase I inhibitor-based ADC, an ORR of 52% was reported with datopotamab deruxtecan. Thirteen confirmed CR/PRs with one additional CR/PR awaiting confirmation and stable disease were reported in nine additional patients after a median follow-up of 8.8 months (range, 4 -- 13 months). A DCR of 81% was observed in this subgroup of patients.

"Despite recent advances in the treatment of triple negative breast cancer, a significant need remains to improve patient outcomes, underscoring the importance of developing new and effective therapies," said Ian E. Krop, MD, PhD, Associate Chief, Division of Breast Oncology, Susan F. Smith Center for Women's Cancers, Dana Farber Cancer Institute. "These preliminary results with datopotamab deruxtecan in pre-treated patients with metastatic triple negative breast cancer are very encouraging and further evaluation of this TROP2 directed ADC is warranted."

The overall safety profile of datopotamab deruxtecan in TNBC in TROPION-PanTumor01 was consistent with what has been previously reported with no new safety signals. Treatment emergent adverse events (TEAEs) occurring in ?15% of patients included nausea, stomatitis, vomiting, fatigue, alopecia, mucosal inflammation, constipation, headache, decreased lymphocyte count, decreased neutrophil count, pyrexia, anemia, pruritis, hypokalemia, diarrhea and cough. Grade 3 or greater treatment-related TEAEs occurred in 23% of patients. No cases of interstitial lung disease (ILD) were observed.

"These updated results continue to show the promise of datopotamab deruxtecan as a durable treatment strategy for patients with previously treated triple negative breast cancer, a historically difficult-to-treat form of breast cancer," said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. "We are committed to further developing datopotamab deruxtecan and establishing where this specifically engineered TROP2 may be most effective in treating triple negative breast cancer."

"Patients with metastatic triple negative breast cancer face rapid disease progression with currently available treatment options and unmet need remains high for these patients," said Cristian Massacesi, MD, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca. "Based on these encouraging results of datopotamab deruxtecan in the triple negative breast cancer cohort of TROPION-PanTumor01, plans are underway to initiate a registrational phase 3 study."

Patients were treated with a median of three prior therapies in the metastatic setting (range, 1-10), including taxanes (91%), platinum-based chemotherapy (52%), immunotherapy (43%), topoisomerase I inhibitor-based ADCs (30%; sacituzumab govitecan, n=10; trastuzumab deruxtecan, n=2; patritumab deruxtecan, n=1) and PARP inhibitors (16%). As of data cut-off on July 30, 2021, 30% of patients remained on treatment with datopotamab deruxtecan.

Summary of TROPION-PanTumor01 TNBC Results

All TNBC Patients without Prior TopoisomeraseEfficacy Measure Patients I-Based ADC and with Measurable Disease (n=44)i, (n=27)ii

ORR, % 34% (n=15) 52% (n=14)

(CR/PR) (confirmed) n=14 n=13

(CR/PR) (pending n=1iii n=1iiiconfirmation)

SD, % 39% (n=17) 33% (n=9)

PD, % 18% (n=8) 15% (n=4)

DCR, % 77% (n=34) 81% (n=22)

CR; complete response; DCR, disease control rate; ORR, objective response rate;PD, progressive disease; PR, partial response; SD, stable disease



i Includes response evaluable patients who had ?1 postbaseline tumor assessmentor discontinued treatment. Postbaseline tumor assessments were not yetavailable for 2 patients at the data cut-off. Three patients were not confirmedto have a target lesion per BICR and therefore had a best overall response ofnon-CR/non-PD.

ii Includes response evaluable patients who had ?1 postbaseline tumorassessment or discontinued treatment. Postbaseline tumor assessments were not

yet available for 1 patient at the data cut-off.

iii Includes patients with an unconfirmed response but are ongoing treatment.