- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Efficacy and safety of lurbinectedin (LUR) with irinotecan (IRI) in patients (Pts) with relapsed small cell lung cancer (SCLC): Results from a phase 2 expansion cohort. (Hall A; Poster Bd #: 356) - Apr 24, 2024 - Abstract #ASCO2024ASCO_3352; P1/2, P3 ORR will be analyzed using a Cochran-Mantel-Haenszel test at a 2-sided 1% alpha level, and OS will be analyzed using a log-rank test at a 2-sided 4% significance level, under a 2-look group sequential design. The LUR/IRI combination showed promising antitumor activity and a manageable safety profile in these pts with poor prognosis, particularly those with CTFI>30 d. These encouraging results reinforce the rationale for including this combination as an experimental arm in the ongoing pivotal phase 3 LAGOON trial (NCT05153239) in relapsed SCLC with CTFI>30 d.
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Trial completion date, Trial initiation date, Trial primary completion date, Metastases: Neoadjuvant Lurbinectedin and Preoperative Radiation for Treating Soft Tissue Sarcomas (clinicaltrials.gov) - Apr 23, 2024 P1/2, N=70, Not yet recruiting, These results reinforce the rationale for assessing the activity of LUR combined with IRI in SS and other tumor types. Trial completion date: Oct 2031 --> Jul 2027 | Initiation date: Apr 2024 --> Jul 2024 | Trial primary completion date: Oct 2026 --> Jan 2026
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Phase classification: Lurbinectedin + Doxorubicin In Leiomyosarcoma (clinicaltrials.gov) - Apr 16, 2024 P1/2, N=62, Recruiting, Trial completion date: Jan 2028 --> Feb 2029 | Trial primary completion date: Jul 2026 --> Apr 2027 Phase classification: P1b/2 --> P1/2
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Enrollment open, Trial completion date, Trial primary completion date, Real-world evidence, Real-world: EMERGE 402: To Assess the Effectiveness and Safety of Zepzelca in Adult Patients With Extensive Stage Small Cell Lung Cancer (SCLC) (clinicaltrials.gov) - Apr 9, 2024 P=N/A, N=300, Recruiting, Phase classification: P1b/2 --> P1/2 Active, not recruiting --> Recruiting | Trial completion date: Jan 2026 --> Jun 2030 | Trial primary completion date: Oct 2025 --> Jun 2030
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Lurbinectedin induces multimodal immune activation and augments the anti-tumor immune response in small-cell lung cancer (Ballroom 20 CD - Upper Level - Convention Center) - Mar 5, 2024 - Abstract #AACR2024AACR_8780; We provide the first mechanistic insight into the lurbinectedin-induced multimodal immune modulation in SCLC leading to a dramatic anti-tumor activity accompanied by the establishment of a strong anti-tumor immune microenvironment. Since lurbinectedin is already approved as a second-line agent in SCLC, our preclinical data provide a strong rationale for combining this regimen with inhibitors of the PD-L1 pathway and also highlight the immune subsets that the combination targets.
- |||||||||| ONC212 / Chimerix, Zepzelca (lurbinectedin) / PharmaMar, Jazz
Synergistic combinations of lurbinectedin with ONC212 in pancreatic cancer (Section 23) - Mar 5, 2024 - Abstract #AACR2024AACR_6706; We also recently discovered a synergistic interaction between lurbinectedin and ONC201/TIC10, a novel compound that induces the TRAIL apoptotic pathway, in small cell lung cancer cell lines...We further hypothesize a combination of lurbinectedin and ONC212 will sensitize the tumor cells to CD8+ T-cell killing, which will be examined via co-culture assays. Our results are developing insights into a novel combinatorial therapeutic regimen while investigating the molecular mechanisms underlying synergism.
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Chk1/2 inhibition enhances response to lurbinectedin treatment in small cell lung cancer (Section 23) - Mar 5, 2024 - Abstract #AACR2024AACR_5325; Western blot analysis of intracellular proteins from the same SCLC cell lines treated with both drugs demonstrate dose-dependent effects on cell death marker cPARP, DNA damage marker ?H2AX, and DDR/cell cycle pathway kinases cdk1 and 2. Ongoing experiments seek to replicate results using alternative Chk1/2 inhibitors, and to explore the effect of lurbinectedin-Chk1/2 inhibitor combination treatment on antitumor immune effector function by in vitro co-culture.
- |||||||||| ecubectedin (PM14) / PharmaMar, PM54 / PharmaMar
Ecubectedin and PM54 demonstrate antitumor activity in patient-derived xenograft models of soft tissue sarcoma (Section 22) - Mar 5, 2024 - Abstract #AACR2024AACR_3941; Xenografted mice were randomized to six treatment groups: 1) vehicle (VEH) (5% dextrose) 5 mL/kg once weekly (QW) intravenously (IV); 2) DOX 5 mg/kg QW IV; 3) trabectedin (TRA) 0.15 mg/kg QW IV; 4) LUR 0.18 mg/kg QW IV; 5) ECU 1.2 mg/kg QW IV; 6) PM54 1.2 mg/kg QW IV... Novel drugs exhibit promising results in the PDX models tested, supporting ongoing exploration in additional PDX models of synovial sarcoma and dedifferentiated liposarcoma.
- |||||||||| onvansertib (PCM-075) / Cardiff Oncology
The PLK1 inhibitor, onvansertib, synergizes with paclitaxel in small cell lung cancer (Section 25) - Mar 5, 2024 - Abstract #AACR2024AACR_2726; P2 The PLK1 inhibitor onvansertib in combination with paclitaxel showed synergy in multiple SCLC cell lines in vitro and potent anti-tumor activity in cisplatin-sensitive and -resistant SCLC PDX models in vivo. Tumor tissue analysis is underway to detail the mechanisms of this interaction.
- |||||||||| Yondelis (trabectedin) / Otsuka, PharmaMar, Valeo Pharma, J&J
Journal: In-Silico Identification of Novel Pharmacological Synergisms: The Trabectedin Case. (Pubmed Central) - Feb 28, 2024 Genes coherently modulated by the drugs were involved in cell cycle, PPARalpha, and Rho GTPases pathways. Our in-silico approach for drug synergism identification showed that trabectedin modulates specific pathways that are shared with other drugs, suggesting possible synergisms.
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Trial completion, Trial completion date, Trial primary completion date, Monotherapy, Metastases: Lurbinectedin Monotherapy in Participants With Advanced or Metastatic Solid Tumors (EMERGE-201) (clinicaltrials.gov) - Feb 26, 2024 P2, N=47, Completed, Our in-silico approach for drug synergism identification showed that trabectedin modulates specific pathways that are shared with other drugs, suggesting possible synergisms. Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Dec 2023 | Trial primary completion date: Mar 2024 --> Dec 2023
- |||||||||| Tracleer (bosentan) / J&J, Roche, Zepzelca (lurbinectedin) / PharmaMar, Jazz
P1 data, PK/PD data, Journal, Metastases: Impact of a Moderate CYP3A4 Inducer (Bosentan) on Lurbinectedin Pharmacokinetics and Safety in Patients with Advanced Solid Tumors: An Open-Label, Two-Way, Crossover, Phase Ib Drug-Drug Interaction Study. (Pubmed Central) - Feb 24, 2024 No differences in terms of toxicity were found between LRB with and without BOS. In summary, the magnitude of the observed changes precludes a clinically relevant effect of BOS co-administration on LRB exposure and its safety profile.
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Review, Journal: A Comprehensive Review on the Role of Lurbinectedin in Soft Tissue Sarcomas. (Pubmed Central) - Feb 19, 2024 However, preclinical and phase I and phase II trials have demonstrated the efficacy of lurbinectedin in different tumor types, including STS. The better understanding of the pathophysiology and evolution of STS as well as the mechanism of action of lurbinectedin in addition to the available data regarding the activity of this drug in this subset of patients will pave the way to newer therapeutic options and strategies.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Zepzelca (lurbinectedin) / PharmaMar, Jazz
Trial primary completion date: LUPER: Lurbinectedin (PM01183) Combined With Pembrolizumab in Small Cell Lung Cancer. (clinicaltrials.gov) - Feb 15, 2024 P1/2, N=28, Active, not recruiting, The better understanding of the pathophysiology and evolution of STS as well as the mechanism of action of lurbinectedin in addition to the available data regarding the activity of this drug in this subset of patients will pave the way to newer therapeutic options and strategies. Trial primary completion date: Feb 2024 --> Sep 2023
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz, Tecentriq (atezolizumab) / Roche
Clinical outcomes to second-line treatment, after failing chemoimmunotherapy, in ES-SCLC (Congress Hall Foyer) - Feb 6, 2024 - Abstract #ELCC2024ELCC_535; The most frequent 2L regimens were Lurbinectedin (32%), re-challenge with Carboplatin/Etoposide (21%), CAV (Cyclophosphamide/ Doxorubicin/ Vincristine) (20%), and Topotecan (9%)...Conclusions Following CIO in the first-line context, 2L survival outcomes resemble those of previously published chemotherapy-alone first-line patients. In this multicentre cohort, 2L-treatment response and survival remain poor in ES-SCLC, suggesting a limited residual impact of immunotherapy.
- |||||||||| 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.
- |||||||||| 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,
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