On March 19, 2025 Servier, an independent global pharmaceutical group governed by a non-profit foundation, and Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with cancer, reported a strategic worldwide licensing agreement for BDTX-4933, a potential best-in-class targeted therapy for solid tumors (Press release, Black Diamond Therapeutics, MAR 19, 2025, View Source [SID1234651252]). Under this global agreement, Servier will develop and commercialize BDTX-4933, a small molecule designed by Black Diamond Therapeutics to address unmet medical needs in RAF/RAS-mutant solid tumors.

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"At Servier, we are dedicated to transforming patient care in areas with significant unmet needs. Our partnership to develop BDTX-4933 is an important opportunity in targeted cancer therapies, as we believe we can serve more people by helping the right patients find the right treatment, at the right time," said Claude Bertrand, Executive Vice-President of R&D at Servier. "We look forward to accelerating the development of this therapy as a potential best-in-class treatment for cancer patients."

"This agreement supports our mission to advance oral cancer therapies designed to give patients the opportunity for longer, healthier, and more active lives," said Mark Velleca, M.D., Ph.D., President and Chief Executive Officer of Black Diamond Therapeutics. "Servier’s commitment to innovation and deep expertise in oncology make it an ideal partner for Black Diamond as we work to develop breakthrough cancer treatments."

Under the terms of the agreement, Servier will lead the development activities and the worldwide commercialization of BDTX-4933 across multiple indications, including non-small cell lung cancer (NSCLC), with potential applications in other solid tumors. Black Diamond Therapeutics will receive an upfront payment of $70 million and will be eligible to receive up to $710 million in development and commercial sales milestone payments, along with tiered royalties based on global net sales.

Currently in Phase 1 development, BDTX-4933 is uniquely designed to target RAS and RAF alterations in solid tumors. The dose escalation and expansion cohort first-in-human study aims at evaluating safety and tolerability, the preliminary recommended Phase 2 dose, and antitumor activity of BDTX-4933 in adults with recurrent advanced/metastatic cancers harboring BRAF, CRAF, or NRAS mutations.

On March 19, 2025 Daiichi Sankyo (TSE:4568) reported that DATROWAY (datopotamab deruxtecan) has been launched in Japan for the treatment of adult patients with hormone receptor (HR) positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) unresectable or recurrent breast cancer after prior chemotherapy (Press release, Daiichi Sankyo, MAR 19, 2025, View Source [SID1234651236]).

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DATROWAY is the first ever TROP2 directed medicine to be launched in Japan for HR positive, HER2 negative breast cancer and is the second DXd antibody drug conjugate (ADC) available based on Daiichi Sankyo’s DXd ADC Technology.

Marketing approval of DATROWAY was granted by the Japan Ministry of Health, Labour and Welfare (MHLW) in December 2024 based on the results from the TROPION-Breast01 phase 3 trial where DATROWAY significantly reduced the risk of disease progression or death by 37% compared to investigator’s choice of chemotherapy (hazard ratio [HR]=0.63, 95% confidence interval [CI]: 0.52-0.76; p<0.0001) in patients with HR positive, HER2 negative metastatic breast cancer as assessed by blinded independent central review (BICR). Median progression-free survival (PFS) was 6.9 months in patients treated with DATROWAY compared to 4.9 months in those treated with chemotherapy.

"HR positive, HER2 negative unresectable or recurrent breast cancer has historically been treated with conventional chemotherapy after progression with hormone therapy, which is associated with poor response rates and a low five-year survival rate," said Kei Kiuchi, Vice President, Oncology Marketing Department, Japan Business Unit, Daiichi Sankyo. "Patients now will have access to DATROWAY, the first TROP2 directed medicine available in Japan for this specific type of metastatic breast cancer."

In TROPION-Breast01, adverse reactions occurred in 93.6% (337/360 patients) of the 360 patients (including 31 Japanese patients) in the DATROWAY (6 mg/kg) arm. The most common adverse reactions included nausea (51.1%), stomatitis (50.0%), alopecia (36.4%), fatigue (23.6%) and dry eye (21.7%). In Japanese patients, interstitial lung disease (ILD) occurred in 6.5% of patients treated with DATROWAY. DATROWAY is approved in Japan with a Warning for ILD. As cases of ILD, including fatal cases, have occurred in DATROWAY-treated patients, DATROWAY is to be used in close collaboration with a respiratory disease expert. Patients should be closely observed during therapy by monitoring for early signs or symptoms of ILD (such as dyspnea, cough or fever) and performing periodical percutaneous oxygen saturation (SpO2) tests, chest X-ray scans and chest CT scans. If abnormalities are observed, discontinue administration of DATROWAY and take appropriate measures, such as corticosteroid administration. Prior to initiation of DATROWAY therapy, a chest CT scan should be performed and medical history taken to confirm the absence of any comorbidity or history of ILD with the patient and carefully consider the eligibility of the patient for DATROWAY therapy.

Additional regulatory submissions for DATROWAY in breast cancer are under review in the EU, China and other regions.

About TROPION-Breast01

TROPION-Breast01 is a global, randomized, multicenter, open-label phase 3 trial evaluating the efficacy and safety of intravenous DATROWAY (6 mg/kg) once per 21-day cycle versus investigator’s choice of singleagent chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine) in adult patients with unresectable or metastatic HR positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who progressed on and are not suitable for endocrine therapy per investigator assessment and have received at least one additional systemic therapy for unresectable or metastatic disease.

Following disease progression or discontinuation of DATROWAY or chemotherapy, patients had the option to receive subsequent treatment at the discretion of their physician. Crossover between trial arms was not permitted.

The dual primary endpoints of TROPION-Breast01 are PFS as assessed by BICR and overall survival (OS). Key secondary endpoints include overall response rate, duration of response, investigator-assessed PFS, disease control rate, time to first subsequent therapy and safety. The PFS data and additional results for key secondary endpoints of TROPION-Breast01 were published in the Journal of Clinical Oncology. The OS data were presented at a Virtual Plenary session hosted by the European Society for Medical Oncology in February 2025.

TROPION-Breast01 enrolled 732 patients in Africa, Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov.

About Hormone Receptor Positive, HER2 Negative Breast Cancer

Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally.1 In Japan, breast cancer is the most common cancer in women, with approximately 92,000 cases diagnosed in 2022.2 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis.

Approximately 70% of diagnosed cases are considered what has been historically called HR positive, HER2
negative breast cancer (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-).3 Endocrine therapy is
widely given consecutively in the early lines of treatment for HR positive metastatic breast cancer.
However, after initial treatment, further efficacy from endocrine therapy is often limited. The current
standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates
and outcomes.

About DATROWAY

DATROWAY (datopotamab deruxtecan; datopotamab deruxtecan-dlnk in the U.S. only) is a TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, DATROWAY is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. DATROWAY 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, DXd) via tetrapeptide-based cleavable linkers.

DATROWAY is approved in Japan and the U.S. for the treatment of adult patients with unresectable or metastatic HR positive, HER2 negative breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on the results from the TROPION-Breast01 trial.

About the DATROWAY Clinical Development Program

A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of DATROWAY across multiple cancers, including non-small cell lung cancer, triple negative breast cancer and HR positive, HER2 negative breast cancer. The program includes eight phase 3 trials in lung cancer and five phase 3 trials in breast cancer evaluating DATROWAY as a monotherapy and in combination with other anticancer treatments in various settings.

On March 19, 2025 Imugene Limited (ASX:IMU), a clinical-stage immuno-oncology company, reported that the US Food and Drug Administration (FDA) has granted Fast Track Designation to its allogeneic CAR T-cell therapy, azer-cel (azercabtagene zapreleucel), for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (Press release, Imugene, MAR 19, 2025, https://mcusercontent.com/e38c43331936a9627acb6427c/files/016deafa-b80d-5bf6-262c-0e50c1d6128c/Azer_cel_Granted_FDA_Fast_Track_Designation_in_Blood_Cancer.pdf [SID1234651235]).

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The FDA’s Fast Track Designation is designed to facilitate the development and expedite the review of drugs that address serious or life-threatening conditions and meet an unmet medical need. Benefits of this designation include more frequent meetings with the FDA to discuss development plans, the option for rolling review of regulatory submissions, and potential eligibility for Accelerated Approval and Priority Review upon meeting relevant criteria.

Azer-cel is an off-the-shelf, CD19-directed CAR T-cell therapy engineered to overcome the logistical challenges of autologous CAR T therapies, such as prolonged manufacturing times and limited patient access. By leveraging pre-manufactured donor T-cells, azer-cel allows for rapid treatment delivery. Clinical data from the ongoing Phase 1b trial has demonstrated significant promise to date, particularly in patients who failed multiple prior therapies including autologous CAR T.

The therapy incorporates a novel combination of lymphodepletion chemotherapy and interleukin-2 (IL-2) to enhance CAR T persistence and efficacy. Azer-cel has shown a manageable safety profile, with no instances of immune effector cell-associated neurotoxicity syndrome (ICANS) observed in key patient cohorts.

Leslie Chong, Managing Director and CEO of Imugene, commented: "Receiving FDA Fast Track Designation is a testament to the transformative potential of azer-cel for patients battling relapsed or refractory DLBCL. We are committed to working closely with the FDA to bring this important therapy to patients as efficiently as possible."

DLBCL is the most common and aggressive form of non-Hodgkin’s lymphoma, with a significant portion of patients experiencing relapse or resistance to standard treatments. Azer-cel addresses this critical unmet need by offering a novel therapeutic approach for this challenging blood cancer.

On March 19, 2025 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it launched "LUNSUMIO for intravenous infusion 1 mg" and "LUNSUMIO for intravenous infusion 30 mg" (generic name: mosunetuzumab (genetical recombination)) (hereafter, LUNSUMIO), antineoplastic agent / anti-CD20/CD3 humanized bispecific antibody for the treatment of patients with relapsed or refractory follicular lymphoma who have received two or more prior standard therapies (Press release, Chugai, MAR 19, 2025, View Source [SID1234651225]). LUNSUMIO had been approved by the Ministry of Health, Labour and Welfare (MHLW) on December 27, 2024 and was listed on the national health insurance (NHI) reimbursement price list today.

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"Relapsed or refractory follicular lymphoma is a difficult-to-cure disease that repeatedly relapses, and therefore there was a need for new treatment options. LUNSUMIO is expected to provide durable remission with monotherapy, and with a predetermined treatment duration based on each patient’s response to therapy, which can help reduce the burden of treatment on patients. We will strive to promote proper use in order to deliver new value to patients, their families, and healthcare professionals," said Chugai’s President and CEO, Dr. Osamu Okuda.

This approval is based on the results of a Japanese Phase I study with an expansion cohort (FLMOON-1 study) conducted in patients with relapsed or refractory follicular lymphoma who had received two or more prior standard therapies, as well as an overseas Phase I/II clinical trial conducted by Roche in the same patient population. In both studies, the efficacy and safety of this drug were evaluated as a monotherapy. Furthermore, four-year follow-up data from the overseas Phase I/II clinical trial was presented at the 66th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper).

Approval Information

Product name: "LUNSUMIO for intravenous infusion 1 mg" and "LUNSUMIO for intravenous infusion 30 mg"

Generic name: mosunetuzumab (genetical recombination)

Indications: relapsed or refractory follicular lymphoma

Precautions concerning indications:

Treatment with this drug should be targeted at patients who have failed to respond to or have relapsed after two or more standard therapies, including an anti-CD20 monoclonal antibody product.
This drug should be administered to patients diagnosed with Grade 1-3A by a pathologist with sufficient experience.
Dosage and administration:
For adults, the usual dosage of mosunetuzumab (genetically modified) is administered as an intravenous infusion in 21-day cycles as follows:
Cycle 1: 1 mg on Day 1, 2 mg on Day 8, and 60 mg on Day 15
Cycle 2: 60 mg on Day 1
Cycles 3-8: 30 mg on Day 1 of each cycle
After 8 cycles, treatment should be discontinued for patients who achieve a complete response. For patients with stable disease or partial response, treatment may be continued for up to a total of 17 cycles.

Date of approval: December 27, 2024

Date of NHI reimbursement price listing: March 19, 2025

Date of launch: March 19, 2025

Drug price:
LUNSUMIO for intravenous infusion 1 mg　　JPY 83,717 / bottle
LUNSUMIO for intravenous infusion 30 mg　 JPY 2,393,055 / bottle

Reference

Chugai Obtains Regulatory Approval for "LUNSUMIO for Intravenous Infusion" for Relapsed or Refractory Follicular Lymphoma in Japan (Press release December 27, 2024)
View Source

About LUNSUMIO

LUNSUMIO is a CD20/CD3 T cell-engaging bispecific antibody designed to target CD20 on B cells and CD3 on T cells. LUNSUMIO is expected to activate the immune system through cytotoxic T cells and have antitumor effects on CD20 expressing tumor cells. LUNSUMIO has been approved in 61 countries worldwide. LUNSUMIO is currently being developed for the treatment of follicular lymphoma (second-line treatment and previously untreated) and relapsed or refractory aggressive B-cell non-Hodgkin’s lymphoma.

About follicular lymphoma

Follicular lymphoma is a type of lymphoma that occurs when B lymphocytes, a type of white blood cell, become cancerous. At diagnosis, 70-85% of patients reach an advanced stage1. Generally, the progression is slow, and chemotherapy is initially effective, but recurrences occur repeatedly in many cases. Repeated recurrences can make it difficult for existing treatments to be effective, and new highly effective treatments are needed. In Japan, approximately 9,000 people reportedly become afflicted with follicular lymphoma each year.

On March 18, 2025 Alphamab Oncology (stock code: 9966.HK) and CSPC Pharmaceutical Group Co., Ltd. ("CSPC") (Stock Code: 1093.HK) reported that anti-HER2 biparatopic antibody-drug conjugate (ADC) JSKN003 has been granted Breakthrough Therapy Designation by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA). The designation is for the treatment of platinum-resistant recurrent epithelial ovarian cancer (PROC), primary peritoneal cancer, or fallopian tube cancer, not restricted to HER2 expression levels.

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Ovarian cancer (OC) ranks as the third most common gynecologic malignancy in China and continues to show a rising incidence, with the highest mortality rate among all malignant gynecologic tumors. The standard treatment regimens recommended by authoritative guidelines both domestically and internationally include surgery combined with platinum-based chemotherapy and targeted therapy maintenance. However, about 80% of OC cases recur, and eventually progress to platinum-resistant ovarian cancer (PROC), leaving patients with limited effective treatment options and poor prognosis. Non-platinum chemotherapy, with or without bevacizumab, is the standard treatment for PROC. Previous studies have shown that the objective response rate (ORR) of PROC treated with non-platinum chemotherapy is only 10% to 15%. The median progression-free survival (PFS) is only 3 to 4 months, and the median overall survival (OS) approximately 12 months, highlighting an urgent need for new treatment options.

The grant of Breakthrough Therapy Designation is based on the pooled analysis of two clinical studies, JSKN003-101 and JSKN003-102. JSKN003-101 (NCT05494918) is an open-label, multicenter, dose-escalation Phase I clinical study conducted in Australia, enrolling patients with advanced solid tumors expressing HER2 (IHC≥1+) or with HER2 mutations. JSKN003-102 (NCT05744427) is a Phase I/ II study conducted in China. The Phase I part enrolled patients with histologically confirmed HER2 expression (IHC≥1+) or HER2 mutations advanced solid tumors. The Phase II part enrolled patients with advanced solid tumors regardless of HER2 expression or mutation status. Pooled results have demonstrated that JSKN003 monotherapy has a favorable tolerability and safety profile, with promising efficacy signals in patients with advanced PROC, and the efficacy was observed across patients with (IHC 1+/2+3+) or without (IHC 0) HER2 expression, with or without prior bevacizumab and prior PARP inhibitor. Preliminary data from the pooled analysis of these two studies were presented at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress.

The Phase III clinical study of JSKN003 for this indication is currently in the enrollment phase and the study is progressing smoothly. As a novel bispecific ADC, JSKN003 leverages the synergistic mechanism of enzyme catalysis and click chemistry to enhance serum stability and bystander effects, while demonstrating superior efficacy. The grant of Breakthrough Therapy Designation is expected to accelerate the clinical development, review and approval process of JSKN003, enabling more patients with PROC to benefit sooner.

About JSKN003

JSKN003 is an anti-HER2 bispecific antibody-drug conjugate (bis-ADC), which is developed inhouse with Alphamab’s proprietary Glycan-specific conjugation platform. JSKN003 can bind HER2 on the surface of tumor cells and release topoisomerase I inhibitors (TOPIi) through cellular endocytosis, thereby exert anti-tumor effects. Compared with its ADC counterparts, JSKN003 demonstrated better serum stability and stronger bystander effect, which effectively expands the therapeutic window.

Multiple clinical studies at various stages of JSKN003 are currently being conducted in China and Australia. Clinical research results have demonstrated favorable tolerability and safety profile, with promising efficacy of JSKN003 in heavily pretreated patients with advanced solid tumors, especially in patients with HER2-expressing breast cancer, platinum-resistant ovarian cancer (PROC), or high HER2-expressing solid tumors.

In September 2024, the Company entered a licensing agreement with JMT-Bio Technology Co., Ltd. ("JMT-Bio"), a wholly-owned subsidiary of CSPC Pharmaceutical Group Co., Ltd. ("CSPC") (stock code: 1093.HK), pursuant to which, JMT-Bio was granted the exclusive license and sublicense rights to develop, sell, offer for sale and commercialize JSKN003, for the treatment of tumor-related indications (the "Field") in mainland China (excluding Hong Kong, Macau or Taiwan) (the "Territory") and become the sole marketing authorization holder for JSKN003 for the Field in the Territory. Alphamab retains the sole right to supply JSKN003.

(Press release, Alphamab, MAR 18, 2025, View Source [SID1234657003])