- |||||||||| zongertinib (BI 1810631) / Boehringer Ingelheim
Zongertinib demonstrates potent efficacy against cancer cells harboring HER2 non-tyrosine kinase domain mutations (Section 35; Poster Board No: 26) - Mar 25, 2025 - Abstract #AACR2025AACR_8999;
Consistent with our results obtained using Ba/F3 models, HCC4006 HER2 V659E cells were sensitive to HER2 inhibition with zongertinib. Our findings indicate that zongertinib demonstrates comparable or more potent inhibitory activity for HER2 non-TKD mutants (e.g TMD and JMD) as HER2 TKD mutations, providing a potential therapeutic option for patients with these HER2 non-TKD mutant cancers.
- |||||||||| ONC212 / Chimerix, ONC206 / Chimerix, Zepzelca (lurbinectedin) / PharmaMar, Jazz
Preclinical analysis of ONC206 and ONC212 with lurbinectedin in pancreatic cancer (Section 35; Poster Board No: 18) - Mar 25, 2025 - Abstract #AACR2025AACR_8989;
Future studies will analyze whether a combination of lurbinectedin and ONC212 or lurbinectedin and ONC206, another imipridone and chemical analogue of ONC201, proves more efficient at killing pancreatic tumor cells in vitro. Our results are developing insights into novel combinatorial therapeutic regimens while investigating the molecular mechanisms underlying synergism.
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
New therapeutic approaches in NUT carcinoma: An unmet need (Section 34; Poster Board No: 23) - Mar 25, 2025 - Abstract #AACR2025AACR_7780;
LUR offers a biologically informed therapeutic strategy in NC. These findings highlight the importance of leveraging tumor biology to guide treatment development for rare and aggressive cancersCharacteristicsAge38 (0-69)MenWomen44 (63%)26 (37%)ThoracicHead/NeckOther4026 4LocalisedLocally AdvancedMetastatic9 2437MolecularBRD4BRD3OtherUnknown193840
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Lurbinectedin/Irinotecan as a new therapeutic combination for small cell lung cancer (Section 34; Poster Board No: 13) - Mar 25, 2025 - Abstract #AACR2025AACR_7770;
Short term treatment of PDX models, as well as 3D cultures of organoids (PDXDO) and spheroids (CDXDS) and 2D cultures of SCLC cell lines, helped us determine that the treatment causes elevated levels of DNA Damage, a blockade in DNA Replication, and finally apoptosis. The results from this study highlight the relevance of the combination of these two already approved drugs in the treatment of SCLC.
- |||||||||| prexasertib (ACR-368) / Acrivon Therap, dordaviprone (ONC201) / Chimerix, Zepzelca (lurbinectedin) / PharmaMar, Jazz
A novel triple combination therapy in small cell lung cancer targeting DNA damage repair as a mechanism of resistance (Section 15; Poster Board No: 21) - Mar 25, 2025 - Abstract #AACR2025AACR_6846;
Prexasertib is a dual inhibitor of Chk1 and 2, protein kinases in the DDR pathway that regulate downstream cell cycle checkpoint (CCC) proteins particularly implicated in G1/S transition and G2 entry. Synergy scores and western blot data from experiments in four cell lines (H1048, H1882, H1105, H1417) point to the role of the DDR-CCC pathway in SCLC treatment resistance and offer a novel treatment modality for testing in vivo, with the ultimate view to progress into the clinic.
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
PM54, a novel transcription inhibitor with promising broad-spectrum antitumor activity (Section 22; Poster Board No: 25) - Mar 25, 2025 - Abstract #AACR2025AACR_4391;
PM54, a novel synthetic member of the ecteinascidin family, is derived from lurbinectedin, a marine-derived compound recognized for its potential in cancer therapy...Median overall survival (OS) times in PM54-treated groups were markedly longer than in controls, highlighting PM54's potential as an effective therapeutic agent. In conclusion, PM54 demonstrates robust antitumor effects across various cancers by impairing mRNA synthesis and inducing DNA damage, underscoring its therapeutic promise.
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Pan-inhibition of super-enhancer-driven oncogenic transcription by novel synthetic ecteinascidins yields potent anti-cancer activity (Section 21; Poster Board No: 13) - Mar 25, 2025 - Abstract #AACR2025AACR_4369;
Mechanistically, our extensive RNA-seq and chem-map assays reveal that synthetic ecteinascidins significantly suppress SE-mediated oncogene expression in melanoma cells by directly binding to and inhibiting the promoters of genes encoding ubiquitous transcription factors and coactivators that are highly enriched at oncogenic SE sites. Overall, our study provides the first evidence that the clinically approved drug, lurbinectedin, as well as its derivatives, can target and disrupt SE-dependent oncogenes, highlighting their potential as therapeutic options for cancers with transcriptionally heterogeneous landscapes where conventional therapies face significant challenges.
- |||||||||| GQ1033 / GeneQuantum Healthcare, GQ1030 / GeneQuantum Healthcare
Novel EGFR x cMET bispecific ADC GQ1033 and DLL3-ADC GQ1030 demonstrated promising therapeutic efficacy in preclinical studies (Section 16; Poster Board No: 14) - Mar 25, 2025 - Abstract #AACR2025AACR_2968;
Using the platforms, we created a broad ADC library targeting EGFR x cMET and DLL3, combining antibodies with various formats, different linkers, and payloads like MMAE, Eribulin, Exatecan, Lurbinectedin, and TopoIx...In an osimertinib-resistant NSCLC PDX trial, involving ~10 models with diverse EGFR/cMET expression levels, GQ1033 demonstrated robust antitumor activity with an overall ORR of ~70%... GQ1033 and GQ1030, developed through high-throughput screening leveraging our iGDC
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Healthcare Resource Utilization (HCRU), Costs, and Outcomes Among Patients With Extensive-Stage (ES) Small Cell Lung Cancer (SCLC) in the United States: A Retrospective, Real-World Analysis of Administrative Claims Data () - Mar 24, 2025 - Abstract #ISPOR2025ISPOR_1511;
Patients with lung cancer were included if they had a diagnosis of metastatic disease and initiated treatment indicative of ES?SCLC (any first-, second-, or third-line regimen containing carboplatin/cisplatin plus etoposide/irinotecan, or lurbinectedin) between January 1, 2018 and December 31, 2022 (Medicare) or July 31, 2023 (MORE 2 ). These results highlight the substantial financial burden and poor outcomes among patients with ES-SCLC throughout the treatment journey.
- |||||||||| Baituowei (goserelin acetate sustained-release microspheres for injection) / Luye Group
Journal: Nano and liposome cancer chemotherapy: A review of advances in drug delivery with applications. (Pubmed Central) - Mar 21, 2025
The development of efficient and safe co-delivery systems that facilitate the effective transport and precise release of drugs within the cancerous tissues while also elucidating the internalization of nanoparticles into tumor cells and their functional mechanisms represents critical areas for future research. Concurrently, advancements in nanocarriers and tumor treatment are anticipated to yield superior therapeutic outcomes and improved quality of life for cancer patients.
- |||||||||| Imfinzi (durvalumab) / AstraZeneca, Zepzelca (lurbinectedin) / PharmaMar, Jazz, Tecentriq (atezolizumab) / Roche
Review, Journal, PD(L)-1 Biomarker, IO biomarker: Current and future perspectives in extensive-stage small-cell lung cancer. (Pubmed Central) - Mar 17, 2025
Advances in molecular profiling and the identification of biomarkers are aiding in the development of personalized treatment approaches. This review focuses on these recent advancements and emerging strategies in the treatment of ES-SCLC.
- |||||||||| Review, Journal, PD(L)-1 Biomarker, IO biomarker: Top advances of the year: Small cell lung cancer. (Pubmed Central) - Mar 5, 2025
Finally, they conclude with the exciting role of advocacy with the newly formed advocacy group Small Cell SMASHERS, amplifying support for SCLC. In 2024, the scientific revolution for SCLC has arrived, spearheading a new era of change for this disease.
- |||||||||| Risperdal Consta (risperidone depot formulation) / J&J
PK/PD data, Journal: Pharmacokinetics and Safety of a Novel Extended-Release Microsphere Formulation of Risperidone in Patients with Schizophrenia or Schizoaffective Disorder. (Pubmed Central) - Feb 27, 2025
Risperidone extended-release injectable suspension (R-ERIS; marketed as RYKINDO) is a novel immediate-release version of risperidone formulated as extended-release microspheres for biweekly intramuscular injection to treat schizophrenia in adults...Eligible patients (N = 108) 18 to 65 years old were randomized (1:1) to receive IM injections of R-ERIS 25 mg or the comparator, a biweekly risperidone long-acting injectable (BW-RLAI; marketed as RISPERDAL CONSTA) 25 mg for a total of 5 injections...R-ERIS was safe and well tolerated. Overall, R-ERIS exhibited a faster onset and offset than BW-RLAI and statistical analysis of exposure parameters demonstrated bioequivalence at steady state.
- |||||||||| phenelzine / Generic mfg., reboxetine / Generic mfg., Ruoxinlin (toludesvenlafaxine extended release) / Luye Group
Journal: Uncovering the Elusive Structures and Mechanisms of Prevalent Antidepressants. (Pubmed Central) - Feb 27, 2025
Their modes of binding are investigated by molecular docking, revealing the essential contacts and conformational changes into the biologically active state. This study underscores the combined use of MicroED and molecular docking to uncover elusive drug structures and mechanisms to aid in further drug development pipelines.
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Lurbinectedin-induced Pneumonitis and DAH in Recurrent Stage IV SCLC: Possible Pulmonary Toxicity From a Novel Alkylating Agent (Area K, Hall F (North Building, Exhibition Level), Moscone Center; Poster Board # P1283) - Feb 24, 2025 - Abstract #ATS2025ATS_1494;
Lurbinectedin has become a preferable second-line option in recurrent stage IV SCLC due to its favorable side-effect profile and non-inferior efficacy, particularly in the elderly population1,5,7. As its use become increasingly common, more investigation is needed to further explore this novel drug's potential pulmonary toxicity14.
- |||||||||| Pozenveo (poziotinib) / Assertio
Journal: The Brain-Penetrant Pan ErbB Inhibitor Poziotinib Effectively Targets HER2+ Breast Cancer Brain Metastases. (Pubmed Central) - Feb 11, 2025
Despite effective HER2-targeted treatments of peripheral HER2+ breast cancer with trastuzumab and HER2 inhibitors, limited brain permeability renders these treatments inefficient for HER2+ breast cancer brain metastasis (BCBM)...The clinical receptor tyrosine kinase inhibitor (RTKi) lapatinib blocked phosphorylation of all ErbB receptors (ErbB1-4) and induced the intrinsic apoptosis pathway in BCBM94...Two weeks of poziotinib treatment successfully ablated BCBM94 and BT474 HER2+ brain tumors in vivo. In conclusion, this study established a patient-derived HER2+ BCBM model and identified poziotinib as highly efficacious RTKi with excellent brain penetrability that eliminated HER2+ BCBM.
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Trial completion date, Trial primary completion date: Palliative Radiotherapy with Lurbinectedin in Patients with Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - Jan 30, 2025
P1, N=22, Recruiting,
In conclusion, this study established a patient-derived HER2+ BCBM model and identified poziotinib as highly efficacious RTKi with excellent brain penetrability that eliminated HER2+ BCBM. Trial completion date: Jan 2025 --> Jul 2025 | Trial primary completion date: Jan 2025 --> Jul 2025
- |||||||||| Review, Journal: Emerging treatments for sarcoma: from 2024 onward. (Pubmed Central) - Jan 28, 2025
While these strategies have demonstrated some success, the overall improvements in survival have often been modest, irrespective of the therapeutic modality. This underscores critical concerns regarding the true cost-benefit balance and the potential for adverse effects, particularly when evaluated over extended follow-up periods.
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Elucidating the Role of ISL1 as a Predictive Biomarker for Lurbinectedin Response in Small Cell Lung Cancer (Grand Ballroom A-C) - Jan 28, 2025 - Abstract #IASLCTTLC2025IASLC_TTLC_190;
We hypothesize ISL1 regulates SOX5 and ASCL1 to cooperate in bending of the minor groove to permit lurbinectedin incorporation into the SCLC DNA, resulting in cell death and exquisite sensitivity to the drug. Mechanistic studies assessing ISL1's role to induce DNA damage by COMET assay, ISL1's interaction with SOX5 at the minor groove of DNA within SCLC, and elucidating ISL1's role to dictate neuroendocrine subtype plasticity are underway.
- |||||||||| stenoparib (2X-121) / Allarity Therap, Oncoheroes
Biomarker, Trial initiation date: Biomarker Directed Trial of Temozolomide and Stenoparib in Relapsed SCLC (clinicaltrials.gov) - Jan 28, 2025
P2, N=152, Not yet recruiting,
Mechanistic studies assessing ISL1's role to induce DNA damage by COMET assay, ISL1's interaction with SOX5 at the minor groove of DNA within SCLC, and elucidating ISL1's role to dictate neuroendocrine subtype plasticity are underway. Initiation date: Jan 2025 --> Jun 2025
- |||||||||| Imfinzi (durvalumab) / AstraZeneca, Zepzelca (lurbinectedin) / PharmaMar, Jazz
Enrollment change, Trial completion date, Trial primary completion date: Durvalumab and Lurbinectedin for the Treatment of Relapsed or Refractory Small Cell Lung Cancer (clinicaltrials.gov) - Jan 4, 2025
P2, N=46, Recruiting,
www.clinicaltrials.gov, identifier is NCT05664932. N=106 --> 46 | Trial completion date: Nov 2025 --> Nov 2026 | Trial primary completion date: Nov 2024 --> Nov 2025
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Journal: Lurbinectedin sensitizes PD-L1 blockade therapy by activating STING-IFN signaling in small-cell lung cancer. (Pubmed Central) - Dec 18, 2024
Interestingly, our study shows that lurbinectedin treatment upregulates MHC-I/II genes and CD8 in SCLC clinical samples. We provide mechanistic insights into the effect of lurbinectedin on STING-mediated multimodal immune activation and demonstrate that lurbinectedin treatment represents a promising therapeutic strategy to potentiate the efficacy of immunotherapy in SCLC.
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Journal, Combination therapy: Unveiling the Mechanism of Lurbinectedin's Action and Its Potential in Combination Therapies in Small Cell Lung Cancer. (Pubmed Central) - Dec 5, 2024
Understanding the mechanism of action (MoA) has facilitated the rational combination of lurbinectedin and anticancer therapies with complementary modes of action, in order to obtain synergistic effects that could potentially lead to improved efficacy. This review evaluates the MoA for lurbinectedin and provides an overview of the therapeutic landscape with regards to lurbinectedin combination therapies for the treatment of SCLC based on data from preclinical and clinical studies.
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Enrollment change, Trial withdrawal, Metastases: Neoadjuvant Lurbinectedin and Preoperative Radiation for Treating Soft Tissue Sarcomas (clinicaltrials.gov) - Nov 18, 2024
P1/2, N=0, Withdrawn,
This review evaluates the MoA for lurbinectedin and provides an overview of the therapeutic landscape with regards to lurbinectedin combination therapies for the treatment of SCLC based on data from preclinical and clinical studies. N=70 --> 0 | Not yet recruiting --> Withdrawn
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