On March 31, 2025 Daiichi Sankyo reported first patient has been dosed in the DESTINYGastric05 phase 3 trial evaluating ENHERTU (trastuzumab deruxtecan) in combination with a fluoropyrimidine chemotherapy (5-FU or capecitabine) and Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy KEYTRUDA (pembrolizumab) versus trastuzumab in combination with platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine) and pembrolizumab in previously untreated patients with unresectable, locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) cancer with PD-L1 CPS ≥1 (Press release, Daiichi Sankyo, MAR 31, 2025, View Source [SID1234651693]). An exploratory cohort of patients with PD-L1 CPS <1 will be randomized to either ENHERTU plus fluoropyrimidine or trastuzumab plus platinum-based chemotherapy.

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ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

Gastric cancer is associated with a poor prognosis, particularly in advanced stages of the disease where the five-year survival rate is 5% to 10%. 1 Current recommended first-line treatment for HER2 positive advanced gastric cancer with PD-L1 CPS ≥1 is trastuzumab in combination with platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine) and pembrolizumab. 2,3 New treatment strategies are needed to continue to improve survival, including additional HER2 directed treatment options.

"Following the positive overall survival results seen with DESTINY-Gastric04 in the second-line HER2 positive metastatic gastric cancer setting, the DESTINY-Gastric05 trial will explore the role of ENHERTU earlier in the metastatic setting as a first-line treatment," said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. "With DESTINY-Gastric05, we are evaluating whether a potential platinum-free chemotherapy regimen of ENHERTU combined with immunotherapy and a fluoropyrimidine chemotherapy can further improve survival in patients with previously untreated HER2 positive metastatic gastric cancer."

ENHERTU is currently approved in more than 65 countries in the second-line or third-line metastatic setting of HER2 positive gastric cancer based on DESTINY-Gastric01, a randomized phase 2 trial, and DESTINYGastric02 and DESTINY-Gastric06, two single-arm phase 2 trials. KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About DESTINY-Gastric05

DESTINY-Gastric05 is a global, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) in combination with a fluoropyrimidine-based chemotherapy (5-FU or capecitabine) and Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy KEYTRUDA (pembrolizumab) versus trastuzumab in combination with platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine) and pembrolizumab in approximately 576 previously untreated patients with unresectable, locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or GEJ cancer with PD-L1 CPS ≥1.

The primary endpoint is progression-free survival (PFS) as assessed by blinded independent central review. The key secondary endpoint is overall survival. Additional secondary endpoints include PFS as assessed by investigator, objective response rate, duration of response and safety.

An exploratory cohort of 150 patients with PD-L1 CPS <1 will be randomized to either ENHERTU plus fluoropyrimidine (5-FU or capecitabine) or trastuzumab plus platinum-based chemotherapy (cisplatin plus 5- FU or oxaliplatin plus capecitabine).

DESTINY-Gastric05 will enroll patients across multiple sites in Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov.

About HER2 Positive Gastric Cancer
Gastric (stomach) cancer is the fifth most common cancer worldwide and the fifth leading cause of cancerrelated death.
4 Approximately one million cases were diagnosed in 2022.4 Gastric cancer is associated with a poor prognosis, particularly in advanced stages of the disease where the five-year survival rate is 5% to 10%.

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors, including gastric cancer.5 Approximately one in five gastric cancers globally are HER2 positive.Recommended first-line treatment for HER2 positive advanced gastric cancer with PD-L1 CPS ≥1 is trastuzumab in combination with platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine) and pembrolizumab.2,3 In patients with PD-L1 CPS <1 recommended first-line treatment is trastuzumab plus platinum-based chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine). 2 New treatment strategies, including additional HER2 directed treatment options, are needed to continue to improve survival in patients with previously untreated advanced gastric cancer.

On March 31, 2025 Calidi Biotherapeutics Inc. (NYSE American: CLDI) ("Calidi"), a clinical-stage biotechnology company developing a new generation of targeted immunotherapies, reported its fourth quarter and full-year 2024 operating and financial results and reviewed recent business highlights (Press release, Calidi Biotherapeutics, MAR 31, 2025, View Source [SID1234653217]).

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"Calidi continues to make great progress on all three of our platforms; our systemic asset CLD-400 proved it can deliver a gene therapy payload to targeted tumors, we filed an IND for our solid tumor asset CLD-201, and our CLD-101 program treating high-grade glioma is advancing in two Phase 1 trials," said Allan Camaisa, CEO and Chairman of the Board of Calidi Biotherapeutics. "We think our multi-modal mechanism of action is a game changer in treating multiple deadly cancers, including metastatic cancer and lung cancer, solid tumors and high-grade glioma."

Fourth Quarter 2024 and Recent Corporate Developments

New data showed that a single dose of a tumor-selective triple knockout ("3KO") RT virus genetically engineered to encode a specific immune-boosting payload (undisclosed) increased the antitumor immune response. These increased shifts in immune composition, driven by virotherapy encoding a payload, ultimately led to complete eradication of certain tested tumors in the preclinical model.
In March 2025, Calidi filed an IND for a company sponsored, open label dose escalation trial of CLD-201 in adult patients with solid tumors, specifically with the indications of breast cancer, head & neck squamous cell carcinoma, and soft tissue sarcoma.
In February 2025, Northwestern University hospital started recruiting for the CLD-101 Phase 1 clinical trial in patients with newly diagnosed high-grade glioma, an aggressive and often fatal form of brain cancer. This physician-led and NCI sponsored clinical trial, led by prominent experts Dr. Maciej Lesniak and Dr. Roger Stupp, builds on the promising results from a prior Phase 1 trial involving 12 patients treated with a single dose of CLD-101 published in the prestigious journal The Lancet Oncology.
City of Hope and Calidi announced the 14th patient treated in a physician-sponsored Phase 1 trial assessing the safety and feasibility of a multi-dosing regimen to treat recurrent high-grade glioma. This program has secured $12 million award from the California Institute for Regenerative Medicine (CIRM) to support this groundbreaking study.
Upcoming Anticipated Milestones

Q2 2025: Payload and lead candidate information revealed on CLD-400 systemic platform
Q2 2025: First patient dosed in CLD-101 Phase 1 trial in collaboration with Northwestern University for newly diagnosed high-grade glioma patients
Q3 2025: First patient dosed in CLD-201 Phase 1 trial
Fourth Quarter 2024 Financial Results

The company reported a net loss attributable to common stockholders of $4.1 million, or $0.27 per share, for the three months ended December 31, 2024, compared to a net loss attributable to common stockholders of $8.2 million, or $0.23 per share, for the same period in 2023.

Research and development expenses were $1.8 million for the three months ended December 31, 2024, compared to $4.0 million for the comparable period in 2023, respectively.

General and administrative expenses were $2.2 million for the three months ended December 31, 2024, compared to $5.9 million for the comparable period in 2023, respectively.

Full Year 2024 Financial Results

The company reported a net loss attributable to common stockholders of $23.8 million, or $2.97 per share, for the year ended December 31, 2024, compared to a net loss attributable to common stockholders of $29.2 million, or $17.33 per share, for the year ended December 31, 2023.

Research and development expenses were $8.9 million for the year ended December 31, 2024, compared to $13.0 million for the year ended December 31, 2023, respectively.

General and administrative expenses were $12.9 million for the year ended December 31, 2024, compared to $16.0 million for the year ended December 31, 2023, respectively.

The company had approximately $9.6 million in cash and $0.2 million in restricted cash as of December 31, 2024, compared to $1.9 million in cash and $0.2 million in restricted cash as of December 31, 2023.

On March 31, 2025 Genmab A/S (Nasdaq: GMAB) reported that the European Commission (EC) has granted marketing authorization for TIVDAK (tisotumab vedotin), an antibody-drug conjugate (ADC), as monotherapy treatment for adult patients with recurrent or metastatic cervical cancer with disease progression on or after systemic therapy (Press release, Genmab, MAR 31, 2025, View Source [SID1234651675]). TIVDAK is the first and only ADC to be granted European Union (EU) marketing authorization for people living with recurrent or metastatic cervical cancer.

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Despite progress in cervical cancer prevention and early detection, there remains a high need for new treatment options, particularly in advanced forms of the disease. In fact, cervical cancer is the fourth most common cause of cancer death among women globally.i In the European Union, cervical cancer is the 11th most frequently occurring cancer among women.ii Up to 15% of adults with cervical cancer present with metastatic disease at diagnosisiii,iv and, for those diagnosed at earlier stages who receive treatment, up to 61%v will experience disease recurrence. For these patients, the prognosis can be poor.vi

"Recurrent or metastatic cervical cancer is a devastating disease, and patients can face a difficult treatment journey with limited options," said Ignace Vergote, M.D., Ph.D., University Hospitals Leuven, co-founder of European Network of Gynaecological Oncological Trial groups (ENGOT), and lead investigator on the innovaTV 301 clinical trial. "In clinical trials, TIVDAK demonstrated a superior overall survival benefit and manageable safety profile compared to chemotherapy, supporting its position to become a potential new standard of care in this setting with a novel mechanism of action. This approval is an important step forward in the treatment landscape for advanced cervical cancer."

The approval is supported by data from the global, randomized, Phase 3 innovaTV 301 trial (NCT04697628) that evaluated the efficacy and safety of TIVDAK compared to chemotherapy in patients with advanced or recurrent cervical cancer who were previously treated with chemotherapy. The trial met its primary endpoint of overall survival (OS), demonstrating a 30% reduction in risk of death (HR: 0.70 [95% CI: 0.54-0.89], two-sided p=0.0038) compared to chemotherapy. Median OS was 11.5 months [95% CI: 9.8-14.9] among patients treated with TIVDAK compared to 9.5 months [95% CI: 7.9-10.7] for patients who received chemotherapy. Secondary endpoints of progression-free survival (PFS) and confirmed objective response rate (ORR) were also met, further validating its clinical benefit. PFS results were statistically significant, with TIVDAK demonstrating a 33% reduction in the risk of disease progression compared with chemotherapy (HR: 0.67 [95% CI, 0.54-0.82], p<0.0001). Data from the innovaTV 204 (NCT03438396) pivotal Phase 2 single-arm clinical trial evaluating TIVDAK as monotherapy in patients with previously treated recurrent or metastatic cervical cancer was also included in the marketing authorization application (MAA).

The most common (≥25%) adverse reactions, including laboratory abnormalities, in patients receiving tisotumab vedotin were peripheral neuropathy (39%), nausea (37%), epistaxis (33%), conjunctivitis (32%), alopecia (31%), anaemia (27%), and diarrhoea (25%).

"We recognize the urgent need to accelerate science and innovate new treatment options for gynecologic cancers, including cervical cancer," said Brad Bailey, Executive Vice President and Chief Commercial Officer of Genmab. "The European Commission approval of TIVDAK marks a milestone in our work to transform the treatment paradigm and help improve outcomes for patients. As the first medicine that Genmab will bring to patients in Europe independently, we’re committed to bringing this important option to as many patients in Europe with previously treated recurrent or metastatic cervical cancer as possible."

About the innovaTV 301 Trial
The innovaTV 301 trial (NCT04697628) is a global, 1:1 randomized, open-label Phase 3 trial evaluating tisotumab vedotin versus investigator’s choice of single agent chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan or pemetrexed) in 502 patients with recurrent or metastatic cervical cancer who received one or two prior systemic regimens in the recurrent or metastatic setting.

Patients with recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma or adenosquamous histology, and disease progression during or after treatment with chemotherapy doublet +/- bevacizumab and an anti-PD-(L)1 agent (if eligible) are included. The primary endpoint was overall survival. The main secondary outcomes were progression-free survival and objective response rate.

The study was conducted by Seagen, which was acquired by Pfizer in December 2023, in collaboration with Genmab, European Network of Gynaecological Oncological Trial Groups (ENGOT, study number ENGOT cx-12) and the Gynecologic Oncology Group (GOG) Foundation (study number GOG 3057), as well as other global gynecological oncology cooperative groups. For more information about the Phase 3 innovaTV 301 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov.

About Tisotumab Vedotin
Tisotumab vedotin (approved under the brand name TIVDAK in the EU, U.S. and Japan) is an antibody-drug conjugate (ADC) composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Pfizer’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggest that the anticancer activity of tisotumab vedotin is due to the binding of the ADC to TF-expressing cancer cells, followed by internalization of the ADC-TF complex and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, tisotumab vedotin also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.

On March 31, 2025 Abbisko Therapeutics Co., Ltd. ("Abbisko Therapeutics") reported that Merck has exercised the global commercialization option for pimicotinib (ABSK021), with an option exercise fee of USD85.0 million, under the licensing agreement signed in December 2023 (Press release, Merck & Co, MAR 31, 2025, View Source [SID1234651694]). The development represents further deepening of the collaboration, underscoring the unwavering commitment and confidence that both parties possess for the ongoing advancement of pimicotinib.

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In December 2023, Abbisko Therapeutics entered into an exclusive licensing agreement (the "Agreement") with Merck regarding pimicotinib, a CSF-1R inhibitor. Under the terms of the Agreement, Merck initially had an exclusive license to commercialize pimicotinib for all indications in the Chinese mainland, Hong Kong, Macau and Taiwan with an exclusive option for global commercial rights of pimicotinib. Merck now has exercised such option and has the exclusive license to commercialize pimicotinib worldwide. Abbisko Therapeutics has already received the one-time, non-refundable upfront payment of USD70.0 million in February 2024, and is now entitled to receive the additional option exercise fee of USD85.0 million. Additionally, Merck has the option to co-develop pimicotinib for additional indications under certain conditions. In total, Abbisko Therapeutics is eligible to receive up to USD605.5 million in payments, including upfront, development, and commercial milestones, as well as double-digit percentage royalties on annual net sales.

Pimicotinib is a novel, orally administered, highly selective, and potent small molecule CSF-1R inhibitor, independently developed by Abbisko Therapeutics. Pimicotinib’s positive topline results from the Global Phase III MANEUVER Study in tenosynovial giant cell tumor ("TGCT") were successfully released in November 2024, where MANEUVER met the primary endpoint with an objective response rate ("ORR") at Week 25 of 54.0% for pimicotinib compared with 3.2% for placebo (p<0.0001), and treatment with oral, once-daily pimicotinib was well-tolerated with very low rates of discontinuation due to treatment-related adverse events, and with no evidence of cholestatic hepatotoxicity.

Yao-Chang Xu, Chairman and CEO of Abbisko Therapeutics, said, "Pimicotinib represents a key advancement within the emerging class of CSF-1R inhibitors, demonstrating a meaningful clinical efficacy and safety profile that positions it as an innovative treatment option for worldwide TGCT patients. We look forward to deepening our collaboration with the Merck team to expedite the registration process of pimicotinib to bring benefits to patients as quickly as possible."

"Today marks a significant milestone in our partnership with Abbisko as we work together to deliver a potentially best-in-class therapy for patients with TGCT around the world," said Andrew Paterson, Chief Marketing Officer for the Healthcare business sector of Merck. "This collaboration underscores our commitment to advancing new treatment options in rare oncology for patients who need them. With this important step forward, we aim to transform the treatment landscape and offer hope to those living with TGCT, who today have very limited treatment options."

On March 31, 2025, Atara Biotherapeutics, Inc., (the "Company") entered into an Amendment (the "Amendment") to the Amended and Restated Commercialization Agreement dated October 31, 2023 (the "Agreement") with Pierre Fabre Medicament ("Pierre Fabre") (Filing, 8-K, Atara Biotherapeutics, MAR 31, 2025, View Source [SID1234651804]). Under the terms of the Amendment, as of March 31, 2025, the Company has completed the transfer of all manufacturing responsibility to Pierre Fabre and Pierre Fabre will be, at its cost, responsible for manufacturing and supplying tabelecleucel for development and commercialization worldwide. Pierre Fabre has also agreed to assume the costs related to remediation of the third-party manufacturing facility to address the U.S. Food and Drug Administration’s (the "FDA") requests to support resubmission of the BLA for tab-cel.

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In exchange for accelerating the transfer of all manufacturing responsibility and assumption of such remediation costs by Pierre Fabre, among other things, the Company agreed to reduce the amount of certain potential future regulatory and commercial milestone payments under the Agreement. The Amendment did not change any of the royalties the Company is eligible to receive under the Agreement. Pursuant to the Amendment, the Company is now entitled to receive an aggregate of up to $550.0 million in additional potential milestone payments upon achieving certain regulatory and commercial milestones relating to tab-cel, including up to $40.0 million in potential regulatory milestones in connection with the approval by the FDA of a BLA for tab-cel under the terms of the Agreement (as amended by the Amendment).

The foregoing summary of the Amendment does not purport to be complete and is qualified in its entirety by reference to the Amendment, a copy of which will be filed with the Company’s Quarterly Report on Form 10-Q for the period ended March 31, 2025.