- |||||||||| Yondelis (trabectedin) / Otsuka, PharmaMar, Valeo Pharma, J&J, Zepzelca (lurbinectedin) / PharmaMar, Jazz
Review, Journal, Tumor microenvironment: Trabectedin and Lurbinectedin Modulate the Interplay between Cells in the Tumour Microenvironment-Progresses in Their Use in Combined Cancer Therapy. (Pubmed Central) - Jan 27, 2024 Finally, the novel therapeutic venues that are currently under exploration, in combination with a plethora of different immunotherapeutic strategies or specific molecular-targeted inhibitors, are reviewed, with particular emphasis on the usage of immune checkpoint inhibitors, or other bioactive molecules that have shown synergistic effects in terms of tumour regression and ablation. These approaches intend to tackle the complexity of managing cancer patients in the context of precision medicine and the application of tailor-made strategies aiming at the reduction of undesired side effects.
- |||||||||| Pozenveo (poziotinib) / Assertio
Trial completion date, Trial termination, EGFR exon 20, HER2 exon 20, Metastases: ZENITH20: Phase 2 Study of Poziotinib in Participants With NSCLC Having EGFR or HER2 Exon 20 Insertion Mutation (clinicaltrials.gov) - Jan 25, 2024 P2, N=648, Terminated, These approaches intend to tackle the complexity of managing cancer patients in the context of precision medicine and the application of tailor-made strategies aiming at the reduction of undesired side effects. Trial completion date: Dec 2023 --> Apr 2023 | Active, not recruiting --> Terminated; Strategic business decision (unrelated to safety)
- |||||||||| Journal, EGFR exon 20: The Impact of On-Target Resistance Mediated by EGFR-T790M or EGFR-C797S on EGFR Exon 20 Insertion Mutation Active Tyrosine Kinase Inhibitors. (Pubmed Central) - Jan 17, 2024
This report highlights that poziotinib and mobocertinib are susceptible to on-target resistance mediated by EGFR-T790M or -C797S in the background of the most prevalent EGFR exon 20 insertion mutations. Furmonertinib, sunvozertinib, and to a less extent zipalertinib can overcome EGFR-T790M compound mutants, whereas EGFR-C797S leads to covalent inhibitor cross-resistance-robust data that support the limitations of mobocertinib and should further spawn the development of next-generation covalent and reversible EGFR exon 20 insertion mutation active inhibitors with favorable therapeutic windows that are less vulnerable to on-target resistance.
- |||||||||| Imdelltra (tarlatamab) / Amgen
Trial primary completion date: DeLLphi-304: Study Comparing Tarlatamab With Standard of Care Chemotherapy in Relapsed Small Cell Lung Cancer (clinicaltrials.gov) - Jan 3, 2024 P3, N=700, Recruiting, Furmonertinib, sunvozertinib, and to a less extent zipalertinib can overcome EGFR-T790M compound mutants, whereas EGFR-C797S leads to covalent inhibitor cross-resistance-robust data that support the limitations of mobocertinib and should further spawn the development of next-generation covalent and reversible EGFR exon 20 insertion mutation active inhibitors with favorable therapeutic windows that are less vulnerable to on-target resistance. Trial primary completion date: Nov 2024 --> Sep 2025
- |||||||||| Pozenveo (poziotinib) / Spectrum Pharma, Luye Group, foretinib (GSK1363089) / Exelixis, pexmetinib (ARRY-614) / Pfizer
Preclinical, Journal, IO biomarker: Screening of potent RIPK3 inhibitors to attenuate necroptosis and inflammation in mouse traumatic brain injury models. (Pubmed Central) - Jan 3, 2024 In our study, we explored the role of NBCs in neuroprotection after traumatic brain injury. It's effectiveness in traumatic brain injury animal models and favorable safety profiles make it a potential candidate for the advances of new therapies for necroptosis-associated neuroinflammatory disorders.
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz, Tecentriq (atezolizumab) / Roche
Trial completion date, Trial primary completion date, Metastases: 2SMALL: Study to Assess Safety,Tolerability,Efficacy of PM01183 and Atezolizumab in Patients w/ Advanced Small Cell Lung Cancer. (clinicaltrials.gov) - Dec 31, 2023 P1/2, N=184, Recruiting,
- |||||||||| Enrollment open, Metastases: ORIENTA: Organoid-based Functional Precision Therapy for Advanced Breast Cancer (clinicaltrials.gov) - Dec 29, 2023
P2, N=252, Recruiting, It's effectiveness in traumatic brain injury animal models and favorable safety profiles make it a potential candidate for the advances of new therapies for necroptosis-associated neuroinflammatory disorders. Not yet recruiting --> Recruiting
- |||||||||| Journal: In brief: Three new injectable antipsychotic drugs. (Pubmed Central) - Dec 26, 2023
Exposure differences were mainly attributed to body weight, while dose adjustments were not needed for patients of different racial identities. No abstract available
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Lurbinectedin in prostatic small cell and neuroendocrine carcinoma. (Level 1, West Hall; Poster Bd # G14) - Dec 13, 2023 - Abstract #ASCOGU2024ASCO_GU_349; L is a well-tolerated and active treatment option for patients with SC/NEPC. Prospective studies are needed to determine the role of L in the treatment of SC/NEPC.
- |||||||||| Cosela (trilaciclib) / G1 Therap, Zepzelca (lurbinectedin) / PharmaMar, Jazz
SCS-04: Harnessing the Power of the Latest Clinical and Research Advances in SCLC: How to Accelerate Progress and Improve Patient Outcomes With Current and Emerging Therapies (Chicago Ballroom ABCD) - Nov 29, 2023 - Abstract #IASLCNACLC2023IASLC_NACLC_94; However, our research indicates healthcare and practice gaps persist in SCLC, partly due to the nature of the disease, the pace of scientific advancements, and their translation into practice. Addressing these gaps requires well-designed educational programs to improve the knowledge, skills, and competence of oncology and multidisciplinary professionals, ensuring that all patients with SCLC can benefit from the latest therapeutic advances.
- |||||||||| 5-fluorouracil / Generic mfg., Zepzelca (lurbinectedin) / PharmaMar, Jazz, irinotecan / Generic mfg.
Preclinical, Journal, Combination therapy: Preclinical Synergistic Combination Therapy of Lurbinectedin with Irinotecan and 5-Fluorouracil in Pancreatic Cancer. (Pubmed Central) - Nov 28, 2023 We further demonstrate that the triple combination between lurbinectedin, irinotecan, and 5-fluorouracil (5-FU) results in a highly efficient killing of tumor cells. Our results are developing insights regarding molecular mechanisms underlying the therapeutic efficacy of a novel combination drug treatment for pancreatic cancer.
- |||||||||| Review, Journal: Management of Brain Metastases: A Review of Novel Therapies. (Pubmed Central) - Nov 28, 2023
Novel systemic therapies with intracranial utility include new anaplastic lymphoma kinase inhibitors like brigatinib and ensartinib; selective "rearranged during transfection" inhibitors like selpercatinib and pralsetinib; B-raf proto-oncogene inhibitors like encorafenib and vemurafenib; Kirsten rat sarcoma viral oncogene inhibitors like sotorasib and adagrasib; ROS1 gene rearrangement (ROS1) inhibitors, anti-neurotrophic tyrosine receptor kinase agents like larotrectinib and entrectinib; anti-human epidermal growth factor receptor 2/epidermal growth factor receptor exon 20 agent like poziotinib; and antibody-drug conjugates like trastuzumab-emtansine and trastuzumab-deruxtecan. This review highlights the modern multidisciplinary management of BM, emphasizing the integration of systemic and local therapies.
- |||||||||| Avastin (bevacizumab) / Roche, Zepzelca (lurbinectedin) / PharmaMar, Jazz
Enrollment open, Phase classification, Combination therapy: Phase 1b of Lurbinectedin in Combination With Weekly Paclitaxel and Bevacizumab in Platinum-resistant Ovarian Cancer (clinicaltrials.gov) - Nov 18, 2023 P1, N=34, Recruiting, However, outcomes for relapsed SCLC remain suboptimal, particularly for patients with a shorter chemotherapy-free interval and central nervous system metastases. Not yet recruiting --> Recruiting | Phase classification: P1b --> P1
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz, Tecentriq (atezolizumab) / Roche
Phase classification, Enrollment change, Metastases: 2SMALL: Study to Assess Safety,Tolerability,Efficacy of PM01183 and Atezolizumab in Patients w/ Advanced Small Cell Lung Cancer. (clinicaltrials.gov) - Nov 18, 2023 P1/2, N=184, Recruiting, Not yet recruiting --> Recruiting | Phase classification: P1b --> P1 Phase classification: P1 --> P1/2 | N=25 --> 184
- |||||||||| Pozenveo (poziotinib) / Spectrum Pharma, Luye Group, Nerlynx (neratinib) / Puma, Knight Therap, Pierre Fabre
Journal: The uncharted role of HER2 mutant alleles in breast cancer. (Pubmed Central) - Nov 5, 2023 Herein, we discuss the under-explored effects of individual HER2 mutant alleles on therapeutic response, a role for HER2 mutation in metastatic propensity, and differences in patient outcomes in ER+ invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC). The preclinical efficacy of additional agents is also discussed, particularly the pan-HER inhibitor poziotinib.
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Trial completion date, Trial primary completion date: Lurbinectedin + Doxorubicin In Leiomyosarcoma (clinicaltrials.gov) - Oct 31, 2023 P1b/2, N=62, Recruiting, The preclinical efficacy of additional agents is also discussed, particularly the pan-HER inhibitor poziotinib. Trial completion date: Jan 2025 --> Jul 2025 | Trial primary completion date: Jan 2024 --> Jul 2024
- |||||||||| LYB001 / Luye Group
Trial completion date, Trial termination: Efficacy and Safety of COVID-19 Vaccine as Booster Vaccination in Adults 18 Years of Age or Older (clinicaltrials.gov) - Sep 26, 2023 P3, N=3000, Terminated, Trial completion date: May 2028 --> Sep 2027 | Trial primary completion date: Jul 2025 --> Nov 2024 Trial completion date: Jan 2024 --> Jun 2023 | Active, not recruiting --> Terminated; According to the development of the novel coronavirus epidemic situation and the company's R&D decision
- |||||||||| LYB001 / Luye Group
Enrollment change, Trial completion date, Trial initiation date, Trial withdrawal, Trial primary completion date: Immunogenicity and Safety of COVID-19 Vaccine in Population Aged 18 Years and Above (clinicaltrials.gov) - Sep 26, 2023 P2, N=0, Withdrawn, Trial completion date: Jan 2024 --> Jun 2023 | Active, not recruiting --> Terminated; According to the development of the novel coronavirus epidemic situation and the company's R&D decision N=720 --> 0 | Trial completion date: Jun 2024 --> Jun 2023 | Initiation date: Jun 2023 --> Jan 2023 | Not yet recruiting --> Withdrawn | Trial primary completion date: Dec 2023 --> Jun 2023
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Journal, BRCA Biomarker, Metastases: Pooled Safety Analysis of Single-Agent Lurbinectedin in Patients With Advanced Solid Tumours. (Pubmed Central) - Sep 18, 2023 This analysis confirms a manageable safety profile for lurbinectedin in patients with advanced solid tumours. Findings are consistent with those reported in patients with relapsed SCLC, Ewing sarcoma, germline BRCA1/2 metastatic breast cancer, neuroendocrine tumours and ovarian cancer.
- |||||||||| Pozenveo (poziotinib) / Spectrum Pharma, Luye Group, Exkivity (mobocertinib) / Takeda, Nerlynx (neratinib) / Puma, Knight Therap, Pierre Fabre
Journal: Acquired secondary HER2 mutations enhance HER2/MAPK signaling and promote resistance to HER2 kinase inhibition in breast cancer. (Pubmed Central) - Sep 18, 2023 HER2 mutations drive the growth of a subset of breast cancers and are targeted with HER2 tyrosine kinase inhibitors (TKI) such as neratinib...Cells expressing double HER2 mutations exhibited resistance to most HER2 TKIs but retained sensitivity to mobocertinib and poziotinib...Double-mutant cells showed enhanced MEK/ERK signaling, which was blocked by combined inhibition of HER2 and MEK. Together, these findings reveal the driver function of secondary HER2 mutations in resistance to HER2 inhibition and provide a potential treatment strategy to overcome acquired resistance to HER2 TKIs in HER2-mutant breast cancer.
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