- |||||||||| Bavencio (avelumab) / EMD Serono, Trodelvy (sacituzumab govitecan-hziy) / Gilead, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Trial completion date, Trial primary completion date, Tumor mutational burden, Metastases: InCITe: Avelumab With Binimetinib, Sacituzumab Govitecan, or Liposomal Doxorubicin in Treating Stage IV or Unresectable, Recurrent Triple Negative Breast Cancer (clinicaltrials.gov) - Dec 15, 2023
P2, N=150, Recruiting,
Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025
- |||||||||| chloroquine phosphate / Generic mfg., doxorubicin hydrochloride / Generic mfg.
Journal: In Doxorubicin-Adapted Hodgkin Lymphoma Cells, Acquiring Multidrug Resistance and Improved Immunosuppressive Abilities, Doxorubicin Activity Was Enhanced by Chloroquine and GW4869. (Pubmed Central) - Dec 9, 2023
HRSdx cells developed cross-resistance to vinblastine, bendamustin, cisplatin, dacarbazine, gemcitabine, brentuximab vedotin (BV), and ?-radiation...HDLM-2dx acquired cross-resistance to caelyx...Both the autophagy inhibitor chloroquine and extracellular vesicle (EV) release inhibitor GW4869 enhanced doxorubicin activity and counteracted doxorubicin resistance. In conclusion, this study identifies common modulated antigens in HRSdx cells, the associated cross-resistance patterns, and new potential therapeutic options to enhance doxorubicin activity and overcome resistance.
- |||||||||| Elahere (mirvetuximab soravtansine-gynx) / ImmunoGen, Takeda
Journal: Mirvetuximab Soravtansine in FR?-Positive, Platinum-Resistant Ovarian Cancer. (Pubmed Central) - Dec 6, 2023
P3
Among participants with platinum-resistant, FR?-positive ovarian cancer, treatment with MIRV showed a significant benefit over chemotherapy with respect to progression-free and overall survival and objective response. (Funded by ImmunoGen; MIRASOL ClinicalTrials.gov number, NCT04209855.).
- |||||||||| Focus V (anlotinib) / Advenchen, Sino Biopharm
Enrollment closed, Metastases: Phase 1/2a/3 Evaluation of Adding AL3818 to Standard Platinum-Based Chemotherapy in Subjects With Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma (AL3818-US-002) (clinicaltrials.gov) - Nov 8, 2023
P3, N=294, Active, not recruiting,
N=50 --> 10 | Trial completion date: Dec 2025 --> Feb 2024 | Trial primary completion date: Dec 2024 --> Feb 2024 Recruiting --> Active, not recruiting
- |||||||||| CDX-1140 / Celldex, Mobista (CDX-301) / Celldex
Phase I trial of pegylated liposomal doxorubicin chemotherapy in combination with CD40 agonist and Flt3 ligand in metastatic triple-negative breast cancer (Hall 2-3) - Nov 4, 2023 - Abstract #SABCS2023SABCS_645;
P1
Key eligibility criteria are unresectable stage III or stage IV TNBC (ER ?10%, PR ?10%, HER2/neu negative), 1st to 3rd line treatment for metastatic disease (1st line patients need to be PD-L1 negative by 22C3 assay), measurable disease by RECIST 1.1 criteria, consent for pre-treatment and on-treatment biopsies of amenable soft tissue tumor lesions, no prior treatment with an anti-CD40 antibody or a Flt3 ligand, no anthracycline treatment in the metastatic setting, no prior progression while on anthracycline-based therapy or within 6 months of completing neoadjuvant chemotherapy, and no history of non-infectious pneumonitis or current pneumonitis. This trial will enroll up to 45 patients across multiple sites (NCT05029999) and is currently open at University of Texas Southwestern Medical Center, Texas Oncology, University of Chicago, University of Texas San Antonio, Sarah Cannon Research Institute, and Johns Hopkins.
- |||||||||| Rituxan (rituximab) / Biogen, Zenyaku Holdings, Roche
A Multicenter, Prospective Clinical Study of the R-CDOP Regimen in Previously Untreated Non-Hodgkin Lymphoma with High Tumor Burden (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_2156;
P=N/A
Pegylated liposomal doxorubicin (PLD) is a promising alternative drug to the current regimen, with a safety and efficacy profile through the enhanced permeability and retention effect and longer circulation1-3, and especially less cardiotoxic compared with traditional anthracyclines4...The patients received PLD (30-35mg/ m2, d1) plus Rituximab (375mg/m2, d0), Cyclophosphamide (750mg/ m2, d1), Vindesine (3mg/ m2, d1) / Vincristine (1.4mg/m2, d1) and Prednisone (60mg/ m2, d1-5) Q3W for 4 (Limited-stage lymphoma) or 6 (Advanced lymphoma) cycles with an additional 2 cycles of Rituximab therapy... The preliminary results of the study indicate that the R-CDOP regimen is safe and shows promising efficacy for treating TN NHL with a high tumor burden.
- |||||||||| Tecentriq (atezolizumab) / Roche
Trial completion, Trial completion date, Trial primary completion date, Tumor mutational burden, IO biomarker, Metastases: ALICE: Atezolizumab Combined With Immunogenic Chemotherapy in Patients With Metastatic Triple-negative Breast Cancer (clinicaltrials.gov) - Nov 1, 2023
P2, N=68, Completed,
positive PROC. Active, not recruiting --> Completed | Trial completion date: Dec 2028 --> Sep 2023 | Trial primary completion date: Dec 2023 --> Apr 2023
- |||||||||| Adcetris (brentuximab vedotin) / Seagen, Takeda
Trial completion: Brentuximab for Newly Diagnosed Hodgkin Disease (clinicaltrials.gov) - Oct 26, 2023
P2, N=40, Completed,
An inherent treatment bias in favor of first-line taxanes cannot be excluded, thus calling for prospective validation. Active, not recruiting --> Completed
- |||||||||| Journal: Enterolactone and trabectedin suppress epithelial ovarian cancer synergistically via upregulating THBS1. (Pubmed Central) - Oct 22, 2023
In animal experiments, combined use of ENL and Trabe showed superior inhibitory effects to either single agent and significantly suppressed tumor growth, and the overexpression of THBS1 further enhanced the anti-cancer activities of the drug combination group. ENL and Trabe synergistically suppress EOC and THBS1 could remarkably facilitate the synergistic anticancer effects of ENL and Trabe.
- |||||||||| pegylated liposomal doxorubicin / Generic mfg.
Preclinical, Journal: Reexamining the effects of drug loading on the in vivo performance of PEGylated liposomal doxorubicin. (Pubmed Central) - Oct 16, 2023
Moreover, it was even more beneficial for mitigating the undesired biological effects caused by PLDs, through prolonging blood circulation and alleviating cutaneous accumulation in the presence of pre-existing anti-PEG Abs due to less opsonins (e.g. IgM and C3) deposition on per particle. Our results warn that the effects of drug loading would be much more convoluted than expected due to the complex intermediation between nanocarriers and bodies, urging independent investigation for each individual delivery platform to facilitate clinical translation and application.
- |||||||||| pegylated liposomal doxorubicin / Generic mfg.
Regression of an immunologically (Exhibit Hall B) - Sep 27, 2023 - Abstract #SITC2023SITC_1186;
This underlines the significance of combination therapies to overcome resistance to immunotherapy in hard to treat cancer models. Ongoing studies are further defining the specific mechanisms by which DOXIL modulates the TME.
- |||||||||| pegylated liposomal doxorubicin / Generic mfg.
Preclinical, Journal: Drug delivery by sonosensitive liposome and microbubble with acoustic-lens attached ultrasound: an in vivo feasibility study in a murine melanoma model. (Pubmed Central) - Sep 26, 2023
Tumor-bearing mice were randomly assigned to one of the following groups: (1) G1: IMP301 only (n?=?9); (2) G2: IMP301?+?LENS (n?=?9); (3) G3: IMP301?+?MB?+?LENS (n?=?9); (4) G4: DOXIL only (n?=?9); and (5) G5: IMP301 without DOXIL group as a control group (n?=?4)...Therefore, this study effectively demonstrates the feasibility of the synergistic combination of IMP301, MBs, and LENS-application for tumor-targeted treatment. Thus, this study can enable efficient tumor-targeted treatment by combining therapy such as IMP301?+?MBs?+?LENS-application.
- |||||||||| Herceptin (trastuzumab) / Roche
Preclinical, Journal: Efficacy of copper nanoparticles encapsulated in soya lecithin liposomes in treating breast cancer cells (MCF-7) in vitro. (Pubmed Central) - Sep 25, 2023
There are several drugs approved by FDA used in breast cancer treatment like Cyclophosphamide, Doxorubicin Hydrochloride, Femara, Herceptin, etc. Each has several side effects as well as treatment, which limits the use of drugs due to heart failure, pulmonary dysfunction, or immunodeficiency...Some drugs have been approved for use in cancer treatment under the concept of drug delivery, such as Doxil (liposomal loaded doxorubicin)...The cytotoxicity assay showed that the IC of Cu/SLP is smaller than that of free CuNPs. These results give clear evidence of the efficacy of using the combined Cu/SLP rather than CuNPs alone as a model drug carrier prepared from plant origin against cancer, both medically and economically.
- |||||||||| pegylated liposomal doxorubicin / Generic mfg.
Trial completion date, Trial primary completion date: CAELYX (clinicaltrials.gov) - Sep 21, 2023
P2, N=63, Active, not recruiting,
These results give clear evidence of the efficacy of using the combined Cu/SLP rather than CuNPs alone as a model drug carrier prepared from plant origin against cancer, both medically and economically. Trial completion date: Mar 2021 --> Dec 2023 | Trial primary completion date: Mar 2021 --> Dec 2023
- |||||||||| pegylated liposomal doxorubicin / Generic mfg.
Journal: Differences in Physico-Chemical Properties and Immunological Response in Nanosimilar Complex Drugs: The Case of Liposomal Doxorubicin. (Pubmed Central) - Sep 13, 2023
Although the two formulations were "similar", we detected different toxicological effects (profiles) in terms of in vitro toxicity and immunological responses at the level of cytokines release and complement activation (iC3b fragment), that could be correlated with the differences in the physicochemical properties of the formulations. Shedding light on nanosimilar key quality attributes of liposome-based materials and the need for an accurate characterization, including investigation of the immunological effects, is of fundamental importance considering their great potential as delivery system for drugs, genes, or vaccines and the growing market demand.
- |||||||||| pegylated liposomal doxorubicin / Generic mfg.
Journal: Effect of Composition and Size on Surface Properties of Anti-Cancer Nanoparticles. (Pubmed Central) - Sep 13, 2023
In addition, liposomal product manufacturing has been interrupted in the past, as was the case for Doxil (doxorubicin hydrochloride liposome injection)...In addition to interfacial tension, three data analyses were identified as able to distinguish between formulations with variations in PEG, cholesterol, and particle size: (i) polar and non-polar contribution to interfacial tension, (ii) liposomal concentration at which the polar and non-polar components were equal, and (iii) rate of interfacial tension decay after droplet formation, which is indicative of how quickly liposomes migrate from the bulk of the solution to the surface. We demonstrate for the first time that interfacial tension can be used to detect certain liposomal formulation changes, such as PEG content, encapsulated drug presence, and size variability, and may make a useful addition to physicochemical characterization during development and manufacturing of liposomal products.
- |||||||||| Zejula (niraparib) / GSK, J&J, Tecentriq (atezolizumab) / Roche
Trial completion date, Trial primary completion date, IO biomarker: ANITA: Platinum-based Chemotherapy With Atezolizumab and Niraparib in Patients With Recurrent Ovarian Cancer (clinicaltrials.gov) - Sep 13, 2023
P3, N=414, Active, not recruiting,
We demonstrate for the first time that interfacial tension can be used to detect certain liposomal formulation changes, such as PEG content, encapsulated drug presence, and size variability, and may make a useful addition to physicochemical characterization during development and manufacturing of liposomal products. Trial completion date: Jan 2025 --> Jan 2024 | Trial primary completion date: Aug 2024 --> Jan 2024
- |||||||||| pegylated liposomal doxorubicin / Generic mfg.
Journal: Orthogonal Self-Assembly of Amphiphilic Peptide Hydrogels and Liposomes Results in Composite Materials with Tunable Release Profiles. (Pubmed Central) - Sep 10, 2023
However, in one case, positively charged MDPs destabilized negatively charged liposomes and resulted in a unique release profile. Finally, we show that MDP hydrogels substantially decrease the release of chemotherapeutic doxorubicin from its liposomal formulation, Doxil, for 24 h. This work demonstrates the chemical compatibility of amphiphilic, orthogonally self-assembled systems and the range of their drug-delivering capabilities.
- |||||||||| pegylated liposomal doxorubicin / Generic mfg.
Journal: Small-Angle X-ray Scattering for PEGylated Liposomal Doxorubicin Drugs: An Analytical Model Comparison Study. (Pubmed Central) - Sep 7, 2023
This study highlights the technical features of SAXS, which provides structural information at the nanoscale for liposomal drugs. The demonstrated methods are reliable and easy-to-use for the structural analysis of liposomal drugs, which are helpful for a broader application of SAXS in the production and regulation of nanopharmaceuticals.
- |||||||||| pegylated liposomal doxorubicin / Generic mfg.
PK/PD data, Preclinical, Journal: Dose-Dependent Effect of Phenothiazines as Dynamin II Inhibitors on the Uptake of PEGylated Liposomes by Endocytic Cells and In Vivo Pharmacokinetics of PEGylated Liposomal Doxorubicin in Rats. (Pubmed Central) - Sep 7, 2023
An important class of dynII inhibitors that are used clinically are phenothiazines, such as prochlorperazine (PCZ)...This work therefore sought to investigate the impact of clinically relevant concentrations of phenothiazines, PCZ and thioridazine, on in vitro liposome endocytosis and in vivo liposome pharmacokinetics after PCZ infusion in rats...When a clinically relevant dose of PCZ was co-administered with PEGylated liposomal doxorubicin (Caelyx/Doxil) in rats, the pharmacokinetics and biodistribution of liposomes were unaltered. These data suggest that while clinically relevant doses of dynII inhibitors can inhibit the uptake of liposomes by endocytic cells in vitro, they are unlikely to significantly affect the pharmacokinetics of long-circulating, co-administered liposomes.
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