Recently, Professor Ma Fei, Chief Physician, Professor, Doctoral Tutor, and Distinguished Professor of the Yangtze River Scholars Program at the Cancer Hospital of the Chinese Academy of Medical Sciences, as the national Leading PI of the ADC drug ESG401 clinical trial developed by Escugen, will present the research results of ESG401 at the 2024 ESMO Annual Meeting.
Professor Ma Fei highly recognized the excellent efficacy, outstanding safety, and great potential for combination therapy with other drugs of ESG401 in patients with brain metastasis and different subtypes of metastatic breast cancer. He pointed out that ESG401 is highly likely to provide new solutions for clinically urgent problems and unmet clinical needs.
The following is reprinted from Oncology Outlook.
Editor's Note: The 2024 European Society for Medical Oncology (ESMO 2024) Annual Meeting will be held in Barcelona, Spain, from September 13 to 17. At the upcoming ESMO 2024, Professor Ma Fei from the Cancer Hospital of the Chinese Academy of Medical Sciences will present two Mini Oral reports (344MO, 349MO) on the novel Trop-2 antibody-drug conjugate (ADC) ESG401. These two studies not only demonstrate the significant efficacy of ESG401 in HER2-negative breast cancer with brain metastasis but also reveal its broad application potential in different subtypes of metastatic breast cancer. They offer new treatment options for breast cancer patients and pave a new direction for the development and application of Trop-2 ADC drugs. Oncology Outlook has invited Professor Ma Fei to introduce the content of the two studies. We also look forward to his excellent presentations at ESMO 2024, contributing Chinese wisdom and strength to global breast cancer treatment.
Oncology Outlook:
You will present two Mini Orals (344MO, 349MO) at the 2024 ESMO Congress. Could you please introduce the main content of these two Mini Orals for us?
Professor Ma Fei: At the upcoming ESMO Congress, I will present two Mini Orals (344MO, 349MO) to the global community. Both Mini Orals are interim reports on the clinical research results of the same novel Trop-2 ADC—ESG401.
Among them, 344MO showcases the safety and efficacy data of ESG401 in HER2-negative breast cancer patients with brain metastasis at baseline. This analysis included a total of 21 patients with advanced breast cancer and brain metastasis at baseline, of whom 67% had TNBC and 33% had HR+/HER2- breast cancer. The largest brain lesion measured 21 mm. Preliminary results show that among the 17 evaluable patients after ESG401 treatment, 3 patients achieved intracranial complete response (CR), and 4 patients achieved partial response (PR), with an intracranial objective response rate (IC-ORR) of 41% and an intracranial disease control rate (IC-DCR) of 76%. The overall therapeutic response of these patients was consistent with the intracranial response, with an overall objective response rate (ORR) of 53% and an overall disease control rate (DCR) of 71%. Additionally, the safety profile of ESG401 in patients with brain metastasis was consistent with that of the overall population.
Brain metastasis is a clinical challenge in breast cancer treatment. To our knowledge, this study is the first report in the exploratory research on the efficacy of Trop-2 ADC drugs that has enrolled the largest number of patients with brain metastasis and evaluated the efficacy of brain metastasis lesions separately according to objective imaging criteria. The efficacy data obtained in this study are also very encouraging. This has important implications for the treatment of HER2-negative breast cancer with brain metastasis and the development of Trop-2 ADC drugs.
349MO is a report on the overall trial design of the Phase Ia/Ib clinical study of ESG401 and the interim safety and efficacy data of ESG401 in patients with various molecular subtypes and different treatment lines of breast cancer. So far, a total of 144 patients have been enrolled in this study, including 65 patients with HR+/HER2- breast cancer, 47 patients with late-line TNBC, and 28 patients with TNBC untreated in the metastatic phase. The study results show that ESG401 has significant efficacy in all three types of breast cancer patients, with ORRs of 34% and 35% in HR+/HER2- breast cancer and advanced TNBC patients, respectively.
It should be particularly noted that when used as first-line treatment for advanced TNBC, ESG401 achieved a very high disease control rate and response rate as monotherapy, with an ORR of 88% and a DCR of 100%. This objective response rate is higher than the values reported in trials of similar ADCs in combination with chemotherapy and also higher than those reported in trials of immune checkpoint inhibitors in combination with chemotherapy. Meanwhile, due to the good safety profile of ESG401, it also lays a solid foundation for subsequent combination therapy with other drugs to achieve higher efficacy and tolerability.
Oncology Outlook:
In the 344MO study, we have seen the significant efficacy of ESG401 in HER2-negative breast cancer with brain metastasis. For patients currently still under treatment, the longest duration of ESG401 treatment has reached 21.3 months. What do you think this data implies for the future clinical trial design of brain metastasis patients and the treatment expectations of patients?
Professor Ma Fei: With the increasing diversification of breast cancer treatment methods in recent years and the continuous improvement of treatment outcomes, patient survival time has been significantly extended, and the incidence of breast cancer brain metastasis has also increased year by year. However, breast cancer brain metastasis has always been a clinical challenge. Once patients develop brain metastasis, their survival period will be significantly shortened. Although the emergence of new treatment drugs has provided more options for the treatment of brain metastasis in patients with HER2-positive advanced breast cancer (such as ADC drugs, small-molecule TKIs, etc.), progress in the treatment of HER2-negative advanced breast cancer has been slow.
ESG401 has shown encouraging efficacy in patients with HER2-negative advanced breast cancer with brain metastasis, with high objective response rates in both intracranial and extracranial lesions, with an intracranial ORR as high as 41%. In clinical research, patients with brain metastasis are often excluded from most clinical trials due to poor physical condition, shortened life expectancy, or increased safety risks. However, with the increasing incidence of brain metastasis, completely excluding such patients from clinical trials means that the study population will not fully represent the patient group using the drug in clinical practice. This may lead to clinical trial data that cannot fully reflect the benefit-risk profile of the drug in real patients when evaluating the efficacy and safety of the study drug.
ESG401 has included patients with brain metastasis in early clinical trials and has achieved excellent efficacy data. On the one hand, these data bring new treatment opportunities and hope for patients with brain metastasis. On the other hand, they also inspire clinical research of innovative drugs, especially early clinical research. We can explore the treatment of some special subtypes earlier on the basis of theoretical support, bringing solutions to clinically urgent problems.
Oncology Outlook:
The 349MO study explored the efficacy of ESG401 in different subtypes of metastatic breast cancer. The results showed that ESG401 demonstrated promising and durable efficacy in various subtypes of mBC, with particularly significant efficacy in first-line treatment of TNBC. Based on the current Phase Ia/Ib clinical study results, what are your plans for future clinical trials of ESG401? Will you further explore its efficacy and safety in specific patient populations?
Professor Ma Fei: At present, we have explored the efficacy of ESG401 in various molecular subtypes and different treatment lines of breast cancer. Preliminary data indicate that ESG401 has good drug safety and clinical adverse reactions are relatively easy to manage. For TNBC patients who have undergone multiple treatments and have poor baseline conditions, ESG401 also shows good efficacy, especially in first-line treatment of advanced TNBC. Therefore, in the future, we will further explore the treatment of advanced triple-negative breast cancer in the first line.
The Phase III clinical study of ESG401 for the treatment of locally advanced or metastatic HR+/HER2- breast cancer that has progressed during or after endocrine therapy and has received at least one line of chemotherapy in the metastatic phase has been approved and is underway, with active enrollment currently in progress.
For breast cancer patients with brain metastasis (especially those with HER2-negative brain metastasis), the preliminary results of ESG401 have given us great confidence. In the future, we will specifically target the brain metastasis population to rapidly develop clinically accessible drugs, thereby greatly satisfying the clinical treatment needs of patients.
Oncology Outlook:
How do you view the potential role of ESG401 in the treatment of breast cancer? Is it likely to become an important new drug for treating various subtypes of breast cancer? What further research on this drug will your team undertake in the future?
Professor Ma Fei: The current research data indicate that ESG401 is a Trop-2 ADC with good efficacy and excellent safety, and we have high expectations for it. For the second-line treatment of advanced HR+/HER2- breast cancer, we have already launched a national multicenter randomized controlled clinical study comparing ESG401 with chemotherapy, and we look forward to the publication of the study data. Based on the significant efficacy of ESG401 in first-line treatment of advanced TNBC, a Phase III clinical trial of ESG401 for this population is also in the planning stage. If the study can achieve positive results, it will greatly improve the overall diagnosis and treatment efficacy of advanced TNBC and extend patient survival. Brain metastasis is currently a clinical challenge. For HER2- brain metastasis patients, if we can further prove the safety and efficacy of ESG401 with larger sample size data in clinical practice, patients will have new treatment options and the opportunity to extend survival. We look forward to the initiation of related studies.
Professor Ma Fei
Chief Physician, Professor, Doctoral Tutor, Distinguished Professor of the Yangtze River Scholars Program
Director of the Department of Medical Oncology, National Cancer Center/Cancer Hospital of the Chinese Academy of Medical Sciences
Secretary-General of the National Committee for Monitoring the Clinical Use of Antitumor Drugs
Deputy Director of the National Cancer Center's Breast Cancer Expert Committee
Secretary-General of the National Cancer Center's Committee for Standardized Screening and Early Diagnosis and Treatment of Breast Cancer
Expert in the Health China Action Promotion Committee
Deputy Director of the Oncology Pharmacy Branch of the China Pharmacists Association
Deputy Director of the Integrated Oncology Cardiology Branch of the Chinese Anti-Cancer Association
Deputy Director of the Committee for Multiple Primary and Unknown Primary Tumors of the Chinese Anti-Cancer Association
Secretary-General of the Committee for Clinical Research of Oncology Drugs of the Chinese Anti-Cancer Association
Deputy Director of the National Women's Ovary Protection and Anti-Aging Promotion Project Committee
Director-General of the Chinese Gerontological and Geriatric Society's Committee for Geriatric Oncology
Deputy Chairman of the Beijing Breast Disease Prevention and Treatment Society
Director of the Beijing Cancer Treatment Quality Control and Improvement Center's Committee for Chemotherapy Quality Control
Editor-in-Chief of Cancer Innovation
Recipient of the National Science and Technology Progress Award, Second Prize, and honorary titles such as "Top Ten Outstanding Young Doctors in the Capital" and "Chinese Anti-Cancer Association Young Scientist Award"
(Sourced from the Oncology Outlook Editorial Department)
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