「運命なんていくらでも変えられるじゃないか、大丈夫だよ、まかせて!」といえる日を目指して。・・Datopotamab deruxtecan showed promising responses as monotherapy and in combination with Imfinzi in patients with metastatic triple-negative breast cancer in two early trials.

221209付け アストラゼネカ社のプレスリリースより <以下引用> :

 AstraZeneca and Daiichi Sankyo’s TROP2-directed ADC showed an encouraging objective response rate of 32% and a manageable safety profile in patients with metastatic TNBC in TROPION-PanTumor01 Phase I trial

Datopotamab deruxtecan plus Imfinzi demonstrated promising updated results with an objective response rate of 73.6% in 1st-line treatment of patients with metastatic TNBC in BEGONIA Phase Ib/II trial

  1. Updated results from the TROPION-PanTumor01 Phase I trial showed datopotamab deruxtecan (Dato-DXd) continued to demonstrate encouraging responses in patients with heavily pretreated metastatic triple-negative breast cancer (TNBC) and disease progression following standard treatment. Results were presented today at the 2022 San Antonio Breast Cancer Symposium (SABCS) (abstract #P6-10-03).
  2. Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.


 Aditya Bardia, Director, Breast Cancer Research Program, Mass General Cancer Center and Associate Professor of Medicine, Harvard Medical School, and investigator in the TROPION-PanTumor01 trial, said: “Triple-negative breast cancer is the most aggressive subtype of breast cancer with the average survival rate of less than 18 months for patients with pretreated metastatic disease. The durable tumour response and disease control seen with datopotamab deruxtecan in patients with pretreated triple-negative breast cancer are encouraging, particularly in those patients who had not received previous treatment with topoisomerase I inhibitor-based antibody drug conjugate.”

 Datopotamab deruxtecan plus Imfinzi (durvalumab) showed 73.6% ORR in 1st-line treatment of metastatic TNBC
Updated results from the BEGONIA Phase Ib/II trial (n=61) showed datopotamab deruxtecan in combination with Imfinzi demonstrated an ORR of 73.6% (95% CI, 59.7-84.7) in patients with previously untreated, unresectable, locally advanced or metastatic TNBC as assessed by investigator. Among the 53 evaluable patients, there were four CRs and 35 PRs. Responses were observed regardless of PD-L1 expression (low and high tumours) with 82% of patients continuing to respond at the time of data cut-off on 22 July 2022. These data were presented at SABCS on 8 December (abstract #PD11-09).


Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: “The median duration of response of nearly 17 months seen in the TROPION-PanTumor01 trial in these patients reinforces the potential of datopotamab deruxtecan to treat this persistent disease. These results, along with the promising clinical response in combination with Imfinzi seen in the BEGONIA trial, underscore the potential role of this TROP2-directed antibody drug conjugate for patients with triple-negative breast cancer as both a monotherapy and in combinations.”

Mark Rutstein, Global Head, Oncology Clinical Development, Daiichi Sankyo, said: “Five-year survival rates for previously treated metastatic triple-negative breast cancer are significantly lower than other subtypes of breast cancer, underscoring the need for new, durable therapies. We are working with urgency and care to evaluate datopotamab deruxtecan in multiple treatment settings in Phase III trials, including the TROPION-Breast02 1st-line trial in patients with locally recurrent inoperable or metastatic triple-negative breast cancer not candidates for anti-PD-L1 therapy.”


Triple-negative breast cancer
Breast cancer is the most common cancer and one of the leading causes of cancer-related deaths worldwide. More than two million breast cancer cases were diagnosed in 2020 with nearly 685,000 deaths globally.

Approximately 15% of breast cancers are considered triple-negative, which is defined by tumours that test negative for estrogen and progesterone hormone receptors (HRs) and human epidermal growth factor 2 receptor (HER2). TNBC is considered the most aggressive subtype of breast cancer. Compared to patients with other breast cancer subtypes, the prognosis for patients with metastatic TNBC is generally worse with a five-year survival rate estimated at 12% and a median overall survival rate of 12-18 months.

TROP2 (trophoblast cell-surface antigen 2) is a transmembrane glycoprotein that is broadly expressed in several types of solid tumours, including in approximately 80% of TNBC cases. TROP2 expression is an unfavourable prognostic factor for overall survival in all types of breast cancer.


AstraZeneca and Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for the manufacturing and supply of datopotamab deruxtecan.


<以上、 より引用終わり> 

補註: TNBC ・・triple-negative breast cancer; negative for estrogen and progesterone hormone receptors (HRs) and human epidermal growth factor 2 receptor (HER2).

補註: Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads, an exatecan derivative, via tetrapeptide-based cleavable linkers.・・同じく、上記のアストラゼネカ社のプレスリリースから引用。 オリジナルなスクリーニング法を開発してこの抗体を作った私たち(札幌医科大学・分子医学研究部門)は、今、期待して、現在進行中のこの抗体医薬の臨床試験の結果を見つめています。

補註: Imfinzi は抗PD-L1 protein 抗体
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses. (同じく、 より引用)。




全生存期間(Overall Survival ;OS)

無増悪生存期間(Progression Free Survival ;PFS)

癌薬物療法の全生存期間(Overall Survival ;OS)と無増悪生存期間(Progression Free Survival ;PFS)との“乖離(かいり)” が見られる場合があり得ます。なので、臨床研究の結果に関しては、比較的短期間に観察可能な無増悪生存期間(Progression Free Survival ; PFS)だけでなく、全生存期間(Overall Survival ; OS)も必ず含めて、注意深く見ていく必要があります。


補註: 以下もご参照ください:

運命には勇気を***** 贈る言葉: テュケー(運命)にはタルソス(勇気)を、ノモス(法律・習慣・貨幣・お金)にはフュシス(自然本来のもの...
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運命には勇気を***** 贈る言葉: テュケー(運命)にはタルソス(勇気)を、ノモス(法律・習慣・貨幣・お金)にはフュシス(自然本来のもの...








LabOnc研究室 キックオフパーティにて。<以上、 より、引用終わり。

補註230130HH 上記引用の日付けから、すでに11年の歳月が流れた・・今回の私たちの仕事から生まれた癌治療抗体医薬の(近い将来の)市販化は、ひとつの進展であり、これからの発展の方向づけのために良い糸口にはなったと確信している。