A Prospective, Single-arm Clinical Study of Liposomal Mitoxantrone Combination Regimen in the Treatment of Relapsed and Refractory Solid Tumors in Children, Adolescents and Young Adults

The aim of this clinical study is to determine the efficacy and safety of the liposomal mitoxantrone combination regimen in treating relapsed and refractory solid tumors among children, adolescents, and young adults. The key questions it intends to address are:
Can the liposomal mitoxantrone combination regimen improve the objective response rate (ORR) compared to historical data? What are the adverse events associated with this combination regimen? Researchers will administer the liposomal mitoxantrone combination regimen (including capecitabine and anlotinib with specific dosing regimens) to the participants and closely monitor their conditions.
Participants will:
Receive the treatment regimen for 4 - 6 cycles, with each cycle lasting 21 days Undergo regular checkups and tests during the treatment period and follow-up period as per the protocol.
Have their tumor status, blood parameters, and other relevant indicators measured to evaluate the treatment effect and safety.

Start Date01 Feb 2025

Sponsor / Collaborator

Cancer Hospital Chinese Academy of Medical Sciences

ChiCTR2400094549

/ SuspendedNot ApplicableIIT

Clinical study of Mitoxantrone hydrochloride liposome injection combined with bendamustine, etoposide and cytarabine for the preconditioning of autologous hematopoietic stem cell transplantation in patients with lymphoma

Start Date01 Jan 2025

Sponsor / Collaborator

The First Affiliated Hospital of Ningbo University

NCT06758726

/ Not yet recruitingNot ApplicableIIT

Mitoxantrone Hydrochloride Liposome Injection Combined With Bu/Cy Conditioning on Acute Myeloid Leukaemia Patients With Intermediate/Adverse Risk Disease or Persistently Positive MRD Undergoing Allogeneic Haematopoietic Stem-cell Transplantation: a Prospective, Single-center, Exploratory Clinical Study

The goal of this study is to evaluate the efficacy and safety of a conditioning regimen of Mitoxantrone Hydrochloride Liposome in combination with Bu/Cy (M+Bu/Cy) on acute myeloid leukaemia (AML) patients with intermediate/adverse risk disease or persistently positive MRD undergoing allogeneic haematopoietic stem-cell transplantation (allo-HSCT)

Start Date31 Dec 2024

Sponsor / Collaborator

Hematology Hospital of Chinese Academy of Medical Sciences

100 Clinical Results associated with Mitoxantrone liposomal(CSPC Pharmaceutical Group Ltd.)

100 Translational Medicine associated with Mitoxantrone liposomal(CSPC Pharmaceutical Group Ltd.)

100 Patents (Medical) associated with Mitoxantrone liposomal(CSPC Pharmaceutical Group Ltd.)

5,948

Literatures (Medical) associated with Mitoxantrone liposomal(CSPC Pharmaceutical Group Ltd.)

01 Feb 2025·BIOMATERIALS

Napabucasin deactivates STAT3 and promotes mitoxantrone-mediated cGAS-STING activation for hepatocellular carcinoma chemo-immunotherapy

Article

Author: Yu, Shihan ; Li, Yutong ; Gao, Yuqiong ; Li, Zhuo ; Yang, Leilei ; Zou, Yifang ; Zhou, Xinyi ; Wang, Lingzhi ; Bi, Shengnan ; Shi, Jia ; Yu, Zhuo ; Liao, Anqi ; Zhang, Xuemei ; Liu, Xiaobo ; Guo, Jianfeng

The immune resistance of tumor microenvironment (TME) causes immune checkpoint blockade therapy inefficient to hepatocellular carcinoma (HCC). Emerging strategies of using chemotherapy regimens to reverse the immune resistance provide the promise for promoting the efficiency of immune checkpoint inhibitors. The induction of cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) in tumor cells evokes the adaptive immunity and remodels the immunosuppressive TME. In this study, we report that mitoxantrone (MIT, a chemotherapeutic drug) activates the cGAS-STING signaling pathway of HCC cells. We provide an approach to augment the efficacy of MIT using a signal transducer and activator of transcription 3 (STAT3) inhibitor called napabucasin (NAP). We prepare an aminoethyl anisamide (AEAA)-targeted polyethylene glycol (PEG)-modified poly (lactic-co-glycolic acid) (PLGA)-based nanocarrier for co-delivery of MIT and NAP. The resultant co-nanoformulation can elicit the cGAS-STING-based immune responses to reshape the immunoresistant TME in the mice orthotopically grafted with HCC. Consequently, the resultant co-nanoformulation can promote anti-PD-1 antibody for suppressing HCC development, generating long-term survival, and inhibiting tumor recurrence. This study reveals the potential of MIT to activate the cGAS-STING signaling pathway, and confirms the feasibility of nano co-delivery for MIT and NAP on achieving HCC chemo-immunotherapy.

01 Feb 2025·BIOORGANIC CHEMISTRY

Identification of mitoxantrone as a potent inhibitor of CDK7/Cyclin H via structure-based virtual screening and In-Vitro validation by ADP-Glo kinase assay

Article

Author: Patekar, Rohan R ; Bharate, Sandip B ; Somarowthu, Tejaswi

Cyclin-dependent kinases, CDK7 and CDK9 play critical roles in cancer by regulating transcriptional processes essential for cell proliferation and survival. Their dysregulation leads to aberrant gene expression, promoting oncogenic pathways and contributing to tumor growth and progression. This study aimed to identify a new chemotype for CDK7/9 inhibitors using a structure-based virtual screening approach. Our research led to the discovery of mitoxantrone as an inhibitor of CDK7/H and CDK9/T1 from a library of FDA-approved small molecule drugs. Mitoxantrone, a chemotherapy agent used to treat acute nonlymphocytic leukemia, works by disrupting DNA synthesis and repair, thus inhibiting cancer cell growth. The study found that mitoxantrone effectively inhibits both CDK7/H and CDK9/T1 with IC₅₀ values of 0.675 µM and 5.15 µM, respectively, while showing no inhibition of CDK2/E1 (IC₅₀ > 100 µM) in in-vitro ADP-Glo kinase assay. It binds to the ATP pocket of CDK7 and CDK9, forming crucial H-bonds with MET 94 and CYS 106, respectively. It achieves dock scores of - 12.93 and - 12.59 kcal/mol, and MMGBSA binding energies of - 82.87 and - 81.59 kcal/mol, respectively. Molecular dynamics simulations over 100 ns confirmed stable interactions with MET 94 and CYS 106 in the hinge region of CDK7 and CDK9. The active site sequence alignment helped to understand the differential activity of mitoxantrone for CDK7, 9 and 2 inhibitions. The findings of the paper reveal a novel mechanism of mitoxantrone action that may contribute to its anticancer efficacy.

01 Feb 2025·Journal of Environmental Sciences

Catalytic detoxification of mitoxantrone by graphitic carbon nitride (g-C3N4) supported Fe/Pd bimetallic nanoparticles

Article

Author: Lei, Liyu ; Fu, Haoyang ; Ling, Lan ; Xu, Qianyu ; Gu, Jiyuan

The overuse of antibiotics and antitumor drugs has resulted in more and more extensive pollution of water bodies with organic drugs, causing detrimental ecological effects, which have attracted attention towards effective and sustainable methods for antibiotics and antitumor drug degradation. Here, the hybrid nanomaterial (g-C₃N₄@Fe/Pd) was synthesized and used to remove a kind of both an antibiotic and antitumor drug named mitoxantrone (MTX) with 92.0% removal efficiency, and the MTX removal capacity is 450 mg/g. After exposing to the hybrid material the MTX aqueous solution changed color from dark blue to lighter progressively, and LC-UV results of residual solutions show that a new peak at 3.0 min (MTX: 13.2 min) after removal by g-C₃N₄@Fe/Pd appears, with the simultaneous detection of intermediate products indicating that g-C₃N₄@Fe/Pd indeed degrades MTX. Detailed mass spectrometric analysis suggests that the nuclear mass ratio decreased from 445.2 (M⁺1H) to 126.0 (M⁺1H), 169.1 (M⁺1H), 239.2 (M⁺1H), 267.3 (M⁺1H), 285.2 (M⁺1H), 371.4 (M⁺1H) and 415.2 (M⁺1H), and the maximum proportion (5.63%) substance of all degradation products (126.0 (M⁺1H)) is 40-100 times less toxic than MTX. A mechanism for the removal and degradation of mitoxantrone was proposed. Besides, actual water experiments confirmed that the maximum removal capacity of MTX by g-C₃N₄@Fe/Pd is up to 492.4 mg/g (0.02 g/L, 10 ppm).

News (Medical) associated with Mitoxantrone liposomal(CSPC Pharmaceutical Group Ltd.)

18 Nov 2024

·www.prnewswire.com

Actinium Pharmaceuticals Highlights Antibody Radiation Conjugate Program Developments and Reports Financial Results for the Third Quarter 2024

- Aligned with FDA on operationally seamless Phase 2/3 trial for Actimab-A + CLAG-M in relapsed/refractory acute myeloid leukemia - Actimab-A selected for National Cancer Institute's recently opened myeloMATCH precision medicines program for patients with acute myeloid leukemia and myelodysplastic syndromes - Two Iomab-ACT INDs cleared by FDA: Commercial CAR-T trial at University of Texas Southwestern and sickle cell transplant trial at Columbia University; proof-of-concept safety and efficacy data expected in 2025 - Actinium seeking U.S. strategic partner for Iomab-B to conduct dose optimization and head-to-head Phase 3 trial based on FDA guidance in adult patients with active relapsed or refractory acute myeloid leukemia - Accomplished biopharma industry executive June Almenoff, M.D., Ph.D., appointed to Actinium's Board of Directors - Cash and cash equivalents of approximately $78.6 million as of September 30, 2024, is expected to fund operations into 2027 NEW YORK, Nov. 18, 2024 /PRNewswire/ -- Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of Antibody Radiation Conjugates (ARCs) and other targeted radiotherapies, today highlighted recent regulatory and development updates for its Iomab-B, Actimab-A and Iomab-ACT ARC clinical programs as well as its financial results for the third quarter ended September 30, 2024. Iomab-B is a first in class CD45 targeted conditioning agent to enable bone marrow transplant (BMT) and has been studied in over four hundred patients including the completed Phase 3 SIERRA trial for patients with relapsed or refractory acute myeloid leukemia (r/r AML). Actimab-A is a targeted radiotherapeutic that uses the Actinium-225 (Ac-225) isotope payload directed against CD33 with broad potential for development in AML and other myeloid indications including in collaboration with the National Cancer Institute (NCI) under a Cooperative Research and Development Agreement (CRADA). Iomab-ACT is a next-generation CD45 targeted conditioning agent being developed for cell and gene therapies for both malignant and non-malignant hematologic indications. Actinium is executing cutting-edge R&D focused on ARCs and other targeted radiotherapies for blood cancer and solid tumor indications leveraging its strong intellectual property portfolio of 230 patents and patent applications including several patents related to the manufacture of the isotope Ac-225 in a cyclotron. Sandesh Seth, Actinium's Chairman and CEO, stated, "During the third quarter and over the last several weeks, we have made significant progress with our three ARC clinical programs. Actinium is now positioned to advance exciting clinical trials for Actimab-A and Iomab-ACT in large indications with high unmet needs that can deliver impactful clinical data in 2025. Actimab-A's backbone therapy potential is poised to be realized with the operationally seamless Phase 2/3 trial following alignment with the FDA, additional clinical trials being planned under the NCI CRADA including the myeloMATCH program and via our R&D efforts to further elucidate Actimab-A's mutation agnostic mechanism of action. The clinical data anticipated from Iomab-ACT in 2025 from the commercial CAR-T and sickle cell transplant trials has the potential to establish Iomab-ACT as a best-in-class targeted conditioning agent for both malignant and non-malignant hematology indications. In addition, our recent meeting with the FDA regarding Iomab-B established a clear development pathway, which will be incredibly valuable in securing a U.S. strategic partner. Finally, I am delighted to welcome Dr. June Almenoff to our Board of Directors, who brings over 25 years of biopharma industry experience with a proven track record of leading drug development through approvals and executing value enhancing business development transactions." Actimab-A Regulatory and Development Update Actinium met with the FDA in the third quarter and aligned with the FDA on an operationally seamless randomized Phase 2/3 trial to study Actimab-A + CLAG-M In the Phase 2 portion of the study, the Actimab-A dose will be optimized in combination with CLAG-M The Phase 3 portion will study the optimized dose of Actimab-A + CLAG-M versus CLAG-M alone in patients with r/r AML Operationally seamless trial design is expected to reduce the required time and resources compared to separate Phase 2 and Phase 3 trials Actinium continues to evaluate and develop additional Actimab-A clinical trials under its CRADA with the NCI, investigator initiated, or Actinium sponsored studies Actimab-A selected by NCI for recently opened myeloMATCH precision medicine program for patients with AML and myelodysplastic syndrome (MDS) Iomab-ACT Program Update In the third quarter, the FDA cleared the investigational new drug (IND) applications for both the commercial CAR-T study led by the University of Texas Southwestern (UTSW) and the sickle cell trial being led by Columbia University The UTSW commercial CAR-T trial expected to initiate patient enrollment in 1Q 2025 with proof-of-concept clinical data expected by year end Commercial CAR-T sales exceeded $3.5 billion in 2023 with multiple CAR-T therapies approved for patients with lymphomas, leukemias and multiple myeloma Columbia University sickle cell transplant trial to study Iomab-ACT for targeted conditioning prior to BMT for the first time in a non-malignant hematology setting, which is a rapidly growing indication for BMT; patient enrollment expected to commence in the first half of 2025 Iomab-B Regulatory Status and Program Update Actinium is seeking a U.S. strategic partner to advance clinical development of Iomab-B including the Phase 3 trial Actinium met with the FDA in the fourth quarter and aligned on the patient population for the head-to-head Phase 3 trial to evaluate allogeneic BMT using Iomab-B plus a reduced intensity conditioning regimen of fludarabine and total body irradiation (Flu/TBI) versus allogeneic BMT using reduced intensity conditioning comprised of cyclophosphamide plus Flu/TBI Head-to-head Phase 3 trial to enroll adult patients aged 18 and above with active AML with blasts counts greater than 5% and less than 20%, representing a broader patient population than that in the SIERRA trial Dose optimization trial to be completed prior to initiating the head-to-head Phase 3 trial to determine the dose for Iomab-B based on radiation to the bone marrow rather than the maximum tolerable dose of 24 Gy of radiation to the liver as was done in the SIERRA trial based on several interactions with the FDA before starting the SIERRA trial Mr. Seth added, "We are excited by our recent progress and committed to delivering on several milestones in the near-term and throughout 2025. Our current balance sheet provides strong runway into 2027, which enables us to deliver important clinical data and further realize our vision of being a leading fully integrated specialty radiopharmaceutical company." Third Quarter 2024 Financial Results Cash and cash equivalents of approximately $78.6 million as of September 30, 2024. Based on Actinium's current operating plan, cash and cash equivalents are expected to fund operations into 2027. Research and Development Expense, net of reimbursements Research and development expenses of $9.8 million for the three months ended September 30, 2024 decreased $1.8 million from $11.6 million for the three months ended September 30, 2023. The decrease is primarily a result of a decline in Chemistry, manufacturing and controls, or CMC, expenses of $5.5 million and lower consulting expenses of $0.5 million, both due to lower activity in 2024 related to Iomab-B. These declines were partially offset by increased preclinical expenses of $3.9 million. General and administrative expense General and administrative expenses of $2.8 million for the three months ended September 30, 2024 increased by $0.1 million from $2.7 million for the three months ended September 30, 2023, primarily due to higher non-cash stock compensation expense of $0.5 million, partially offset by lower compensation expense of $0.3 million due to lower headcount. In the third quarter of 2024, our overall headcount reduced by approximately twenty percent, with a majority of these former employees being from our clinical and CMC groups. As a result of these departures, we expect our personnel expenses to be reduced by approximately $3.7 million in 2025, which may be offset by additional hires or consultants. We do not expect these departures to have a material impact on our operations or ability to execute our operating plan and we are actively seeking a strategic partner for Iomab-B in the U.S. to advance the clinical development activity for Iomab-B including the planned Phase 3 trial. Other income Other income is comprised of net interest income in both reporting periods. The amount for the three months ended September 30, 2024 and 2023 of $1.0 million in each reporting period was virtually unchanged from the same time period in the prior year. Net loss Net loss of $11.6 million for the three months ended September 30, 2024 decreased by $1.7 million from $13.3 million for the three months ended September 30, 2023 due to lower research and development expenses partially offset by higher general and administrative expenses. About Actinium Pharmaceuticals, Inc. Actinium develops Antibody Radiation Conjugates (ARCs) and other targeted radiotherapies intended to meaningfully improve outcomes for people who have failed existing oncology therapies. The company continues to advance its development for product candidate Actimab-A, a therapeutic agent that has demonstrated potential activity in r/r AML patients. In addition, Actinium is engaged with the National Cancer Institute (NCI) under the Cooperative Research and Development Agreement (CRADA) for development of Actimab-A in AML and other myeloid malignancies. Iomab-ACT, Actinium's next generation conditioning candidate, is being developed with the goal of improving patient access and outcomes for potentially curative cell and gene therapies. Iomab-B is an induction and conditioning agent prior to bone marrow transplant in patients with relapsed and refractory acute myeloid leukemia (r/r AML), which Actinium is seeking a potential strategic partner for in the U.S. In addition, the company's R&D efforts are primarily focused on advancing several preclinical programs for solid tumor indications. Actinium holds 230 patents and patent applications including several patents related to the manufacture of the isotope Ac-225 in a cyclotron. For more information, please visit: Forward-Looking Statements This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time. Investors: [email protected] SOURCE Actinium Pharmaceuticals, Inc. 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Phase 3Financial StatementPhase 2Radiation Therapy

15 Sep 2024

·www.globenewswire.com

Immunocore presents Phase 1 data of brenetafusp, an ImmTAC bispecific targeting PRAME, in patients with ovarian cancer

Immunocore presents Phase 1 data of brenetafusp, an ImmTAC bispecific targeting PRAME, in patients with ovarian cancer Brenetafusp is clinically active as monotherapy and in combination with chemotherapy in heavily pre-treated, platinum-resistant ovarian cancer patients T cell fitness gene expression signature in blood is an important parameter of clinical activity for tebentafusp in uveal melanoma and for brenetafusp across different tumor types 14 September 2024 -- Immunocore Holdings plc (Nasdaq: IMCR) (“Immunocore” or the “Company”), a commercial-stage biotechnology company pioneering and delivering transformative immunomodulating medicines to radically improve outcomes for patients with cancer, infectious diseases and autoimmune diseases, today presented Phase 1 data with brenetafusp in patients with platinum resistant ovarian cancer at the 2024 European Society for Medical Oncology (ESMO) Congress. In a proffered session to be held on Monday, September 16, 2024, the Company will present translational Phase 1/2 data with KIMMTRAK® (tebentafusp-tebn) and brenetafusp demonstrating that T cell fitness gene expression signature in blood is an important parameter associated with clinical activity for both therapies in metastatic uveal melanoma. “Brenetafusp monotherapy is active in heavily pre-treated, platinum resistant ovarian cancer patients and can be combined safely with chemotherapy. We see the hallmarks of ImmTAC clinical activity in this Phase 1 data, such as disease control, ctDNA molecular response, and association with T cell fitness, which increases our confidence in the potential for brenetafusp in ovarian cancer,” said David Berman, Head of Research and Development. “While early, the promising efficacy data from chemotherapy plus brenetafusp led us to expand the combinations we are studying, including in earlier-line platinum sensitive disease.” Dr. Claire Friedman, Gynecologic Medical Oncologist & Early Drug Development Specialist at Memorial Sloan Kettering Cancer Center, said: “While many solid tumors have benefited from the advances in immunotherapy, the treatment of recurrent ovarian cancer has remained an ongoing challenge. These data offer proof of concept that patients with advanced, platinum-resistant ovarian cancer can benefit from brenetafusp, alone or in combination with chemotherapy, and support further development of the drug in this patient population.” Thirty-seven patients with heavily pre-treated (median 5 prior lines) serous ovarian cancer were treated with brenetafusp monotherapy, including four patients previously presented in the efficacy data set at ESMO 2022. A majority of patients had received prior bevacizumab (81%) and PARP inhibitors (59%). Brenetafusp was well tolerated with no treatment-related discontinuation or death observed. The most frequent treatment-related adverse event was reversible and manageable cytokine release syndrome, observed in 57% of patients, with the majority being Grade 1. Thirty-one of the 37 monotherapy patients were evaluable for RECIST v1.1 tumor assessment, 58% of whom demonstrated disease control (partial response and stable disease), including two confirmed partial responses (6.5% RECIST response rate). Of patients who had tumor progression, 64% were treated beyond progression (median of 2 additional months). Across all 37 patients, the median progression-free survival (PFS) was 3.3 months, and the overall survival (OS), while still maturing, was 73% at 6 months. Of the 29 monotherapy patients evaluable for circulating tumor DNA (ctDNA) response, 31% (9/29) had a molecular response (≥0.5 log reduction by week 9). Twenty-eight monotherapy patients were evaluable for baseline blood T cell fitness (TCF) gene expression signature. There was greater activity in patients with a TCF signature above median versus those at or below the median, respectively, including: disease control (80% vs 38%), PFS (3.7 months vs 2.2 months) and six-month OS (93% vs 47%). As presented today at ESMO in a pre-clinical study poster (1021P), the combination of chemotherapy with brenetafusp has the potential to enhance clinical activity by increasing expression of the antigen presentation machinery in cancer cells. In the Phase 1 trial, 16 patients with platinum-resistant ovarian cancer were treated with brenetafusp and either gemcitabine, nab-paclitaxel or pegylated doxorubicin chemotherapy. These patients were heavily pre-treated (median of 4 prior treatment lines) including prior bevacizumab (75%) and PARP inhibitors (75%). The safety profile of brenetafusp in combination with chemotherapy was consistent with the expected profile of each individual agent. Thirteen of the 16 combination patients were evaluable for RECIST v1.1 tumor assessment. All 13 patients received prior platinum and taxane therapy, and 6 received prior gemcitabine. Sixty nine percent (9/13) of patients achieved disease control, including three partial responses (23% RECIST response rate). Historical chemotherapy efficacy data in this heavily pre-treated patient population is sparse but indicate response rates are less than 10%, with disease control rates typically ~40-50%1. Eleven of the 16 combination patients were evaluable for ctDNA response. The molecular response rate was 82% (9/11). As previously reported for brenetafusp in cutaneous melanoma (ASCO 2024), ctDNA molecular response in this trial was also associated with longer OS and PFS. At an oral proffered session on Monday, September 16, 2024, the Company will present translational data from previously treated, metastatic uveal melanoma (mUM) patients, including 132 patients treated with KIMMTRAK in a Phase 1/2 trial, and 22 patients treated with brenetafusp in a Phase 1 trial. In the KIMMTRAK cohort, patients with a TCF signature greater than or equal to the median had higher clinical activity compared to patients with a TCF signature below the median, respectively, including longer OS (28 months vs 11 months), PFS (5 months vs 2 months) and disease control (67% vs 36%). The association of TCF signature with longer OS was independent of known prognostic factors in uveal melanoma. In addition, the TCF signature was associated with greater tumor reduction and a higher rate of on-target, melanocyte-related adverse events; both are consistent with the mechanism of action, and suggest that the signature is not purely prognostic. This TCF signature, discovered for KIMMTRAK in mUM, was subsequently confirmed as an important parameter of clinical activity for brenetafusp in mUM (ESMO 2024), ovarian cancer (ESMO 2024), and cutaneous melanoma (ASCO 2024). The accumulating data suggests that ImmTAC therapies may deliver greater clinical activity in earlier line patients, where TCF is expected to be higher, leading the Company to investigate brenetafusp in these populations. Immunocore’s proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules that are designed to redirect the immune system to recognize and kill cancerous cells. ImmTAC molecules are soluble TCRs engineered to recognize intracellular cancer antigens with ultra-high affinity and selectively kill these cancer cells via an anti-CD3 immune-activating effector function. Based on the demonstrated mechanism of T cell infiltration into human tumors, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumors, regardless of mutational burden or immune infiltration, including immune “cold” low mutation rate tumors. IMC-F106C-101 is a first-in-human, Phase 1/2 dose escalation trial in patients with multiple solid tumor cancers including non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), endometrial, ovarian, cutaneous melanoma, and breast cancers. The Phase 1 dose escalation trial was designed to determine the maximum tolerated dose (MTD), as well as to evaluate the safety, preliminary anti-tumor activity and pharmacokinetics of IMC-F106C (brenetafusp), a bispecific protein built on Immunocore’s ImmTAC technology, and the Company’s first molecule to target the PRAME antigen. The Company is enrolling patients into three expansion arms in ovarian, NSCLC, and endometrial cancers. The IMC-F106C-101 trial is adaptive and includes the option for Phase 2 expansion, allowing for approximately 100 patients treated per tumor type in the Phase 1 and 2 expansion arms. Dose escalation continues in additional solid tumors as well as plans for combination arms with standards-of-care, including checkpoint inhibitors, chemotherapy, and tebentafusp. Most patients with ovarian cancer are diagnosed with advanced disease, giving it the highest mortality amongst gynecological malignancies in the US and Europe. The current standard of care is surgery followed by platinum-based chemotherapy, and although many patients initially respond, the disease often recurs and, over time, becomes resistant to further platinum therapy. There is significant unmet need for new therapies that improve clinical outcomes in both platinum-sensitive and platinum-resistant ovarian cancer patients. Uveal melanoma is a rare and aggressive form of melanoma affecting the eye. Although it is the most common primary intraocular malignancy in adults, the diagnosis is rare, and up to 50% of people with uveal melanoma will eventually develop metastatic disease. Unresectable or metastatic uveal melanoma typically has a poor prognosis and had no approved treatment until KIMMTRAK. KIMMTRAK is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. KIMMTRAK specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma. This is the first molecule developed using Immunocore’s ImmTAC technology platform designed to redirect and activate T cells to recognize and kill tumor cells. KIMMTRAK has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in the United States, European Union, Canada, Australia, and the United Kingdom. Immunocore is committed to helping patients who need KIMMTRAK obtain access via our KIMMTRAKConnect program. The program provides services with dedicated nurse case managers who provide personalized support, including educational resources, financial assistance, and site of care coordination. To learn more, visit KIMMTRAKConnect.com or call 844-775-2273. Immunocore is a commercial-stage biotechnology company pioneering the development of a novel class of TCR bispecific immunotherapies called ImmTAX – Immune mobilizing monoclonal TCRs Against X disease – designed to treat a broad range of diseases, including cancer, autoimmune diseases, and infectious diseases. Leveraging its proprietary, flexible, off-the-shelf ImmTAX platform, Immunocore is developing a deep pipeline in multiple therapeutic areas, including nine active clinical and pre-clinical programs in oncology, infectious diseases, and autoimmune diseases. The Company’s most advanced oncology TCR therapeutic, KIMMTRAK has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in the United States, European Union, Canada, Australia, and the United Kingdom. The content above comes from the network. if any infringement, please contact us to modify.

Clinical ResultImmunotherapyDrug Approval

11 Jun 2024

·www.biospace.com

Actinium Announces Results of Actimab-A + CLAG-M Combination Trial Highlighted in Oral Presentation at the 2024 Society of Nuclear Medicine & Molecular Imaging Annual Meeting

- Novel targeted radiotherapy-based combination being studied as potential backbone therapy potential relapsed or refractory acute myeloid leukemia - Actimab-A + CLAG-M produced high rates of response, measurable residual disease negativity, bone marrow transplant access and improved survival outcomes in high-risk patients including TP53+ and venetoclax treated patients - SNMMI oral presentation highlighted dosimetry results and safety data supporting this novel radiotherapy combination NEW YORK, June 11, 2024 /PRNewswire/ --Actinium Pharmaceuticals, Inc., (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of Antibody Radiation Conjugates (ARCs) and other targeted radiotherapies, today highlighted data from the completed Phase 1b combination trial of Actimab-A + CLAG-M in patients with relapsed or refractory acute myeloid leukemia (r/r AML) at the 2024 Society of Nuclear Medicine & Molecular Imaging (SNMMI) Annual Meeting held June 8 – 11, 2024, in Toronto, Canada. Actimab-A is an ARC comprised of a CD33 targeting monoclonal antibody conjugated with the alpha-particle emitter Actinium-225 isotope payload. Actimab-A has been studied as a single agent and in combination with chemotherapies and targeted therapies in Phase 1 and Phase 2 trials. Sandesh Seth, Actinium's Chairman and CEO, said, "These results demonstrate the immense potential of targeted radiotherapy via ARCs from both an efficacy and safety perspective. Through the use of dosimetry, we can estimate radiation doses to the target organ and non-targeted healthy organs and as observed in this trial, we saw no safety signals for the kidneys, liver or other major organs. Together with the potent efficacy, particularly in these high-risk relapse and refractory patients, we are highly excited by the building clinical pro We look forward to continuing to advance our Actimab-A program as a broad-based combination approach with targeted and non-targeted therapies in collaboration with the NCI for the benefit of AML patients who are eligible for targeted radiotherapy." The Phase 1b Actimab-A + CLAG-M combination trial enrolled patients with high-risk r/r AML with the following features: Median age of 62 with patients up to 73 years old 91% of patients had intermediate (n=3, 13%) or adverse cytogenetics (n=18, 78%) Over 50% of patients had a TP53 mutation Median of 2 lines of prior therapy (range:1-5) including: Prior bone marrow transplant: 57% Prior venetoclax treatment: 57% Despite the high-risk pro the patients on the study, the combination of Actimab-A + CLAG-M produced high rates of response and measurable residual disease negativity and improved survival outcomes across all patient subsets: 64% of eligible patients proceeded to bone marrow transplant with these patients having a median overall of 24 months. Dosimetry and Safety: A validated pharmacokinetic model was used to estimate the biodistribution of Actimab-A based on the distribution of CD33+ AML blast cells based on data derived from patients in the Phase 1b study Across all dose levels including 0.75 µCi/kg, which was determined to be the optimal dose, and 1.0 µCi/kg (the highest dose in the Phase 1b study) radiation doses for key organs were well below known tolerance levels with external beam radiation therapy (EBRT) No safety signals for major organs such as liver, heart, kidneys, lungs and intestines were observed and a safety pro with that expected in heavily pre-treated r/r AML patients given salvage therapy A single 30-minute administration of Actimab-A results in rapid radiation delivery and clearance with peak concentration reached around 0.6 hours and undetectable in the blood by 48 hours after administration The dose of 0.75 µCi/kg was identified as optimal for this combination therapy and will be further evaluated in the next stage of clinical development About the SNMMI Annual Meeting The SNMMI Annual Meeting is recognized as the premier educational, scientific, research, and networking event in nuclear medicine and molecular imaging. The four-day event, taking place each June, provides physicians, technologists, pharmacists, laboratory professionals, and scientists with an in-depth view of the latest research and development in the field as well as providing insights into practical applications for the clinic. About Actinium Pharmaceuticals, Inc. Actinium develops targeted radiotherapies to meaningfully improve survival for people who have failed existing oncology therapies. Advanced pipeline candidates Iomab-B (pre-BLA & MAA (EU)), an induction and conditioning agent prior to bone marrow transplant, and Actimab-A (National Cancer Institute CRADA pivotal development path), a therapeutic agent, have demonstrated potential to extend survival outcomes for people with relapsed and refractory acute myeloid leukemia. Actinium plans to advance Iomab-B for other blood cancers and next generation conditioning candidate Iomab-ACT to improve cell and gene therapy outcomes. Actinium holds more than 230 patents and patent applications including several patents related to the manufacture of the isotope Ac-225 in a cyclotron. For more information, please visit: Forward-Looking Statements This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time. Investors: investorrelations@actiniumpharma.com Company Codes: AMEX:ATNM

Clinical ResultPhase 1Radiation Therapy

100 Deals associated with Mitoxantrone liposomal(CSPC Pharmaceutical Group Ltd.)

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KEGG	Wiki	ATC	Drug Bank
-	Mitoxantrone liposomal(CSPC Pharmaceutical Group Ltd.)	L01DB07	DB01204

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Peripheral T-Cell Lymphoma	CN	CSPC ZhongNuo Pharmaceutical (Shijiazhuang) Co. Ltd.	01 Jun 2021

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Multiple Sclerosis	NDA/BLA	US	Immunex Corp.	01 Feb 2000
Nasopharyngeal Carcinoma	Phase 3	CN	CSPC Hebei Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.	15 Feb 2023
Nasopharyngeal Cancer, Recurrent	Phase 3	-	CSPC ZhongNuo Pharmaceutical (Shijiazhuang) Co. Ltd.	01 Feb 2023
Peripheral T-cell lymphoma unspecified refractory	Phase 3	CN	CSPC Zhongqi Pharmaceutical Technology Shijiazhuang Co., Ltd.	14 Apr 2021
Myeloid Tumor	Phase 2	CN	CSPC ZhongNuo Pharmaceutical (Shijiazhuang) Co. Ltd.	29 Feb 2024
Refractory acute myeloid leukemia	Phase 2	CN	CSPC ZhongNuo Pharmaceutical (Shijiazhuang) Co. Ltd.	29 Feb 2024
Relapsing acute myeloid leukemia	Phase 2	CN	CSPC ZhongNuo Pharmaceutical (Shijiazhuang) Co. Ltd.	29 Feb 2024
Acute Lymphoblastic Leukemia	Phase 2	CN	CSPC Pharmaceutical Group Ltd.	01 Feb 2024
B-cell lymphoma refractory	Phase 2	CN	CSPC Pharmaceutical Group Ltd.	01 Feb 2024
Diffuse large B-cell lymphoma refractory	Phase 2	CN	CSPC Zhongqi Pharmaceutical Technology Shijiazhuang Co., Ltd.	27 Jul 2023

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASH2024	Not Applicable	Non-Hodgkin Lymphoma	-	CMOP±R regimen	nqbsxabzyc(vvheremtqv) = qogpuqwdbx xnzogucorh (viqbeowcoy ) View more	-	08 Dec 2024
ASH2024	Not Applicable	Peripheral T-Cell Lymphoma	-	Lipo-MIT	iuvdxspwnx(lwsqxkuvhy) = neutropenia (66.7%), leucopenia (44.4%), anaemia (33.3%) and thrombocytopenia (11.1%) rajvtnkraz (jraqgoyslq )	-	07 Dec 2024
NCT05620862 (ASCO2024) Manual	Phase 1	Solid tumor	51	Mitoxantrone hydrochloride liposome 24mg/m2vincristineirinotecan	afdytkcjet(nfmkpciocg) = bvodgoxlee mefcoraiaw (vqozwcbpnd ) View more	Positive	24 May 2024
NCT05299164 (phase I study, EHA2024)	Phase 1	Refractory Aggressive Non-Hodgkin Lymphoma	18	GVM±R regimen with Lipo-MIT 16 mg/m2	uqydqxhqyn(wkejpdylzb) = leucopenia (94.4%), neutropenia (88.9%), thrombocytopenia (72.2%), anemia (38.9%), lymphocyte count decreased (38.9%), febrile neutropenia (16.7%) , pneumonia (16.7%) and hypokalemia (11.1%) szezacvnnf (vowhdluinh ) View more	Positive	14 May 2024
NCT05299164 (phase I study, EHA2024)	Phase 1	Refractory Aggressive Non-Hodgkin Lymphoma	18	GVM±R regimen with Lipo-MIT 18 mg/m2		Positive	14 May 2024
ASCO 12023 \| ASCO 22023 Manual	Phase 1	Sarcoma	23	Pegylated liposomal doxorubicin+ifosfamide	swvkevcgbd(nqvwckxfwr) = cvpmaftowc jypjehhlex (bysyctxpkf ) View more	Positive	26 May 2023
P013 (EBMT2023)	Not Applicable	Acute Myeloid Leukemia	20	FLAG-MITOXANTRONE (M)	jrjpbvfwjm(mgwczyhrxq) = rykkecnauf xwfihwzpsq (qaymtzaazs ) View more	-	23 Apr 2023
NCT04509466 (ESMO2022)	Phase 1/2	Extranodal NK-T-Cell Lymphoma	31	Mitoxantrone hydrochloride liposome	usblrivgii(lvbefjrbcx) = luzjssaimh szeiqhgsyu (bdbvlgjlif, 70.2% - 96.4%) View more	-	12 Sep 2022
NCT04902027 (ASCO2022) Manual	Phase 1	Recurrent Head and Neck Carcinoma \| Head and neck cancer metastatic	34	Mitoxantrone hydrochloride liposome	gzzprqobxq(ghulrlsytj) = ofbxedahdl gotkcjofiq (hgvveyequq ) View more	Positive	02 Jun 2022
NCT04902027 (ASCO2022) Manual	Phase 1		34	Mitoxantrone hydrochloride liposome (nasopharyngeal cancer)	echnaxvgcb(acznwuiqkt) = xjhwetfsqg cdztawcqed (ehjfxwlfyr ) View more	Positive	02 Jun 2022
NCT02596373 (Pubmed \| Invest New Drugs)	Phase 2	Advanced breast cancer	-	Lipo-MIT	jhyyqfjlbc(xycnjnmkhk) = sbmeikcbir ctrhqrgqbk (thshkfjfhc, 3.8 - 30.7) View more	-	11 Oct 2021
NCT02596373 (Pubmed \| Invest New Drugs)	Phase 2	Advanced breast cancer	-	MIT	jhyyqfjlbc(xycnjnmkhk) = wctuuhryxt ctrhqrgqbk (thshkfjfhc, 0.8 - 22.1) View more	-	11 Oct 2021
NCT03776279 (CSCO2021)	Phase 2	Peripheral T-Cell Lymphoma \| Extranodal NK-T-Cell Lymphoma	108	Mitoxantrone Hydrochloride Liposome	vuxhnymcva(tkvxcxtavn) = jjmsldxaxj gdhmwblcyn (kwtvzhijcu, 32.3 - 51.5) View more	Positive	25 Sep 2021

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