- |||||||||| 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.
- |||||||||| Avastin (bevacizumab) / Roche, utidelone IV (UTD1) / Beijing Biostar Technologies
Utidelone plus bevacizumab for the treatment of HER2-negative breast cancer brain metastases (U-BOMB): A multicenter, single-arm phase II study. (Hall A; Poster Bd #: 59) - Apr 24, 2024 - Abstract #ASCO2024ASCO_2511;
P2
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. This study preliminarily shows promising efficacy and manageable safety of the combination of utidelone and bevacizumab in the treatment of HER2-negative metastatic breast cancer patients with brain metastases.
- |||||||||| 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
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,
No.NCT03693547; https://classic.clinicaltrials.gov. Active, not recruiting --> Recruiting | Trial completion date: Jan 2026 --> Jun 2030 | Trial primary completion date: Oct 2025 --> Jun 2030
- |||||||||| lithium carbonate ER / Generic mfg.
Journal: Drugs for bipolar disorder. (Pubmed Central) - Apr 9, 2024
Active, not recruiting --> Recruiting | Trial completion date: Jan 2026 --> Jun 2030 | Trial primary completion date: Oct 2025 --> Jun 2030 No abstract available
- |||||||||| Bavencio (avelumab) / EMD Serono, Zepzelca (lurbinectedin) / PharmaMar, Jazz
Enrollment open: Lurbinectedin With or Without Avelumab in Small Cell Carcinoma of the Bladder (LASER) (clinicaltrials.gov) - Apr 4, 2024
P2, N=35, Recruiting,
These results represent the first to confirm the binding of toludesvenlafaxine to DAT in both rats and humans using PET/CT, and its elevation of brain DA level, which may help understand the unique pharmacological and functional effects of triple reuptake inhibitors such as toludesvenlafaxine. Not yet recruiting --> Recruiting
- |||||||||| BA1104 (nivolumab biosimilar) / Luye Group
Enrollment open, Metastases: A Study to Compare the Efficacy and Safety of LY01015 and Opdivo (clinicaltrials.gov) - Mar 15, 2024
P3, N=510, Recruiting,
This finding will better guide the clinical practice of lurbinectedin and provide valuable evidence for future research. Not yet recruiting --> Recruiting
- |||||||||| irinotecan hydrochloride liposome injection (LY01610) / Luye Group
Enrollment open, Trial completion date, Trial initiation date, Trial primary completion date: Study of LY01610 in Patients With Recurrent Small Cell Lung Cancer (clinicaltrials.gov) - Mar 15, 2024
P3, N=686, Recruiting,
Not yet recruiting --> Recruiting Not yet recruiting --> Recruiting
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Enrollment closed, 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) - Mar 5, 2024
P=N/A, N=300, Active, not recruiting,
Additionally, Donepezil and Memantine demonstrate cognitive benefits, as measured by MMSE. Recruiting --> Active, not recruiting
- |||||||||| 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.
- |||||||||| Pozenveo (poziotinib) / Assertio, Enhertu (fam-trastuzumab deruxtecan-nxki) / Daiichi Sankyo, AstraZeneca, Perjeta (pertuzumab) / Roche
HER2 TKIs enhance the anti-tumor activity of HER2-targeting CAR-T and CAR-NK cells against NSCLC (Section 2) - Mar 5, 2024 - Abstract #AACR2024AACR_6967;
Current HER2-targeting approaches, including antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan, have shown promising response rates...We engineered a series of HER2 CAR constructs utilizing scFvs derived from trastuzumab, pertuzumab, and FRP5, recognizing distinct domains of HER2...Using a HER2 YVMA duplication patient-derived xenograft (PDX) NSCLC model, we observed that the in vivo combination of poziotinib with HER2 CAR-NK cells exhibited superior anti-tumor activity as compared to poziotinib treatment alone. In conclusion, HER2 CAR-T and CAR-NK cells effectively target HER2-mutant and HER2-positive NSCLC, and their combination with HER2 TKIs enhances vulnerability to HER2-targeting strategies.
- |||||||||| 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.
- |||||||||| EGFR and mTOR signaling facilitate RET-independent resistance to selective RET-TKIs (Section 25) - Mar 5, 2024 - Abstract #AACR2024AACR_4117;
To determine whether EGFR or MET signaling facilitate RET inhibitor resistance, LC-2/ad and NCCE-TH1101 (KIF5B-RET) NSCLC cells were treated with increasing concentrations of selpercatinib or pralsetinib with or without ligands for these receptors, EGF or HGF respectively, and after five days cell viability was measured by CellTiter Glo...Next, to evaluate whether blockade of EGFR or MET signaling could enhance the activity of RET inhibitors, we treated LC-2/ad and NCCE-TH1101 cells with RET TKIs alone or in combination with the EGFR TKI erlotinib or poziotinib, or the MET inhibitor SU11274...We observed that treatment of LC-2/ad and NCCE-TH1101 cells with an mTOR inhibitor (everolimus) or a MEK inhibitor (trametinib) in combination with RET TKIs increased the anti-tumor activity or RET inhibitors...RET TKI resistant cells were sensitive to mTOR or MEK inhibitors in combination with RET TKIs. Collectively, our findings indicate that in RET-fusion positive NSCLC tumor cells, activation of bypass pathways including the EGFR, MAPK, mTOR pathways may facilitate RET inhibitor resistance and that blockade of bypass pathways may enhance the efficacy of selective RET inhibitors and overcome acquired RET TKI resistance.
- |||||||||| 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, PARP Biomarker, IO biomarker: Recent advances and future strategies in first-line treatment of ES-SCLC. (Pubmed Central) - Feb 23, 2024
This review delves into the current and evolving treatment landscape for ES-SCLC, focusing on the most promising therapeutic strategies under investigation. We discuss the latest developments in the use of newer ICIs, antiangiogenic agents, PARP inhibitors (PARPi), lurbinectedin, and anti-DLL3 agents, offering insights into potential future directions in the management of this aggressive cancer.
- |||||||||| Imdelltra (tarlatamab) / Amgen
Enrollment change, Trial primary completion date: DeLLphi-304: Study Comparing Tarlatamab With Standard of Care Chemotherapy in Relapsed Small Cell Lung Cancer (clinicaltrials.gov) - Feb 21, 2024
P3, N=490, Recruiting,
We discuss the latest developments in the use of newer ICIs, antiangiogenic agents, PARP inhibitors (PARPi), lurbinectedin, and anti-DLL3 agents, offering insights into potential future directions in the management of this aggressive cancer. N=700 --> 490 | Trial primary completion date: Sep 2025 --> Aug 2027
- |||||||||| 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, Combination therapy: 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.
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