- |||||||||| Ruoxinlin (toludesvenlafaxine extended release) / Luye Group
Review, Journal: Efficacy, Tolerability, and Safety of Toludesvenlafaxine for the Treatment of Major Depressive Disorder-A Narrative Review. (Pubmed Central) - Mar 30, 2023
In conclusion, this review highlights the favorable clinical results of toludesvenlafaxine in only two short-term trials that enrolled patients with major depressive disorder (MDD) (efficacy and tolerability were good for up to eight weeks), indicating the need for more good quality, larger-sample, and longer-term trials. Exploring new antidepressants, such as TRI, can be considered a priority for clinical research due to the high rates of TRD, but also due to the significant percentages of relapse in patients with MDD.
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
¿Lurbinectedin? (Twitter) - Mar 30, 2023
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Enrollment change, Trial completion date, Trial termination, Trial primary completion date, Checkpoint inhibition: Immune Checkpoint Inhibition With Lurbinectedin Relapsed/Recurrent SCLC (clinicaltrials.gov) - Mar 27, 2023
P1/2, N=9, Terminated,
Exploring new antidepressants, such as TRI, can be considered a priority for clinical research due to the high rates of TRD, but also due to the significant percentages of relapse in patients with MDD. N=57 --> 9 | Trial completion date: Oct 2025 --> Mar 2023 | Recruiting --> Terminated | Trial primary completion date: Oct 2024 --> Mar 2023; DLTs
- |||||||||| Pozenveo (poziotinib) / Spectrum Pharma, Luye Group
P2 data, Journal, HER2 exon 20: Poziotinib in Treatment-Na (Pubmed Central) - Mar 25, 2023
N=57 --> 9 | Trial completion date: Oct 2025 --> Mar 2023 | Recruiting --> Terminated | Trial primary completion date: Oct 2024 --> Mar 2023; DLTs Poziotinib demonstrated clinically meaningful efficacy with a manageable toxicity profile for treatment-na
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Review, Journal, PD(L)-1 Biomarker, IO biomarker: Emerging Strategies for the Treatment of Small Cell Lung Cancer: A Review. (Pubmed Central) - Mar 21, 2023
For second-line treatment, a novel alkylating agent, lurbinectedin, which inhibits oncogenic transcription, has been approved for use in patients with metastatic SCLC...Advances in research have revealed critical information regarding biologic characteristics of the disease, which may lead to the identification of vulnerabilities and the development of new therapies. Further research focused on identifying biomarkers and evaluating innovative therapies will be paramount to improving treatment outcomes for patients with SCLC.
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Lurbinectedin shows potent activity in all four molecular subtypes of small cell lung cancer (SCLC) and POU2F3 and SLFN11 are biomarkers for a better response (Section 19; Poster Board #17) - Mar 14, 2023 - Abstract #AACR2023AACR_8450;
P2
Trial completion date: Jun 2024 --> Jan 2026 | Trial primary completion date: Jun 2024 --> Oct 2025 The aim of this study was to analyze the activity of lurbinectedin in the different SCLC molecular subtypes and to investigate new biomarkers of response.Methods and Results - We have characterized a panel of 20 SCLC human cell lines based on the expression of ASCL1, NEUROD1, YAP1 and POU2F3, where lurbinectedin yielded a mean IC50 value of 6.52 nM, which is considerable greater than the activity exerted by topotecan, irinotecan, carboplatin, etoposide, olaparib, alisertib and navitoclax (IC50 100
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Lurbinectedin exhibits combinatorial activity with BCL2/BCL2L1 inhibitors in vitro and in vivo by modulation of MCL1 expression (Section 16; Poster Board #17) - Mar 14, 2023 - Abstract #AACR2023AACR_8393;
Correspondingly in vivo, enhancement in the efficacy of lurbinectedin was observed in combination with venetoclax in SCLC models, while in solid tumor models other than SCLC the combination with a specific BCL2L1 inhibitor enhanced efficacy. Collectively, these data identify MCL1 as a specific lurbinectedin target and suggest that combinations that target other pro-survival proteins may represent a viable strategy to enhance the anti-tumor activity of lurbinectedin.
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Exportin 1 inhibition synergizes with lurbinectedin by altering the response to DNA damage in neuroendocrine lung tumors (Section 17; Poster Board #17) - Mar 14, 2023 - Abstract #AACR2023AACR_8340;
These data indicates that inhibition of exportin 1 with selinexor in combination with lurbinectedin is a promising therapeutic strategy in lung NECs. Subsequent In vivo testing in patient-derived xenograft to study efficacy and toxicity of this combination will provide preclinical rationale for clinically exploring this combination in patients with lung NECs who have failed chemotherapy regimen.
- |||||||||| Role of individual HER family members and pan-HER targeting treatment strategy in NRG1 fusion positive cancer (Section 21; Poster Board #16) - Mar 14, 2023 - Abstract #AACR2023AACR_6231;
Treatment with cetuximab, an antibody that targets EGFR, in combination with trastuzumab and pertuzumab yielded a synergistic effect on tumor cell killing. These data indicate that HER4 and EGFR can play a role in NRG1 fusion-driven signaling through crosstalk with HER2/HER3 and thus, pan-HER/EGFR inhibitors are more effective than EGFR/HER2 or HER2/HER4-selective inhibitors, highlighting the therapeutic potential of targeting multiple members of the HER family in NRG1 fusion driven cancers.
- |||||||||| TAS2940 / Otsuka
TAS2940 inhibits intracranial tumor growth and prolongs survival in HER2-aberrant and EGFR-amplified patient-derived xenograft models (Section 20; Poster Board #14) - Mar 14, 2023 - Abstract #AACR2023AACR_6207;
P1
Here, we demonstrate that TAS2940 induces downregulation of phosphorylated HER2/EGFR, reduces tumor burden, and promotes a significant increase in survival in intracranial xenograft mouse models with HER2-amplification (BC), HER2-Exon20 insertion mutation (NSCLC), and EGFR-amplification (GBM). These promising preclinical data highlight potential novel therapeutic strategies for patients with EGFR-aberrant GBM and brain metastases harboring HER2/EGFR alterations, and may help support the advancement of the ongoing first-in-human clinical trial (NCT04982926) for TAS2940 in solid tumors with EGFR and/or HER2 alterations.
- |||||||||| ONC212 / Chimerix, Zepzelca (lurbinectedin) / PharmaMar, Jazz
Synergistic combinations of lurbinectedin with irinotecan and ONC212 in pancreatic cancer (Section 14; Poster Board #10) - Mar 14, 2023 - Abstract #AACR2023AACR_4896;
This is being explored by co-culturing CD8+ T lymphoblast cells with pancreatic tumor cells treated with lurbinectedin, irinotecan, ONC212, and combination, along with molecular mechanisms of cell death and effects on cytokines in the tumor microenvironment. Our results are developing insights regarding molecular mechanisms underlying therapeutic efficacy of a novel combination drug treatment for pancreatic cancer.
- |||||||||| Biochemical inhibition profiles of 370 wild type human kinases provide a basis for selecting alternative combinations of EGFR and VEGFR inhibitors (Section 14; Poster Board #1) - Mar 14, 2023 - Abstract #AACR2023AACR_4887;
Kinase inhibition profiles were measured for 7 agents that were candidate alternatives for cediranib or erlotinib, including: vandetanib, erdafitinib, axitinib, lenvatinib, cabozantinib, poziotinib, and mobocertinib (note: Cmax values varied 58-fold among the drugs)...This project was funded in part with federal funds from the NCI, NIH, under contract no. HHSN261201500003I.
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
High SLFN11 expression correlates with sensitivity to lurbinectedin in small cell lung cancer (SCLC) models (Section 39; Poster Board #19) - Mar 14, 2023 - Abstract #AACR2023AACR_3442;
The in vivo efficacy data confirms that the SLFN11 high NCI-H1048 model is more responsive with 90% TGI compared to 35% observed in SLFN11 low models (NCI-H889 and NCI-H69) at the highest lurbinectedin dose (p-value = 0.006). Efficacy data confirms correlation to SLFN11 protein expression, consistent with the RNA level association.
- |||||||||| Pozenveo (poziotinib) / Spectrum Pharma, Luye Group, Tagrisso (osimertinib) / AstraZeneca
CD70-targeting CAR-T and CAR-NK cells demonstrate potent activity against NSCLC drug-tolerant persister cells (Section 37; Poster Board #6) - Mar 14, 2023 - Abstract #AACR2023AACR_2272;
Furthermore, we determined that CD70-targeting CAR-T and CAR-NK cells showed promising in vitro activity against the DTPCs of osimertinib-treated EGFR mutant NSCLC. These results demonstrate CAR-based cellular therapy as an effective approach to target DTPCs and identify CD70 as a novel therapeutic target for combatting DTPCs in NSCLC.
- |||||||||| Bavencio (avelumab) / EMD Serono, Zepzelca (lurbinectedin) / PharmaMar, Jazz
Trial initiation date, Metastases: Phase II Trial of Lurbinectedin Combined With Avelumab as Switch Maintenance Firstline Therapy (clinicaltrials.gov) - Mar 14, 2023
P2, N=36, Not yet recruiting,
These results demonstrate CAR-based cellular therapy as an effective approach to target DTPCs and identify CD70 as a novel therapeutic target for combatting DTPCs in NSCLC. Initiation date: Jan 2023 --> May 2023
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Cost-Effectiveness Modeling of Lurbinectedin As a Second-Line Therapy in Patients with Small Cell Lung Cancer (SCLC) () - Mar 9, 2023 - Abstract #ISPOR2023ISPOR_894;
Based on a published network meta-analysis, a subgroup analysis in platinum-sensitive patients (chemotherapy-free interval ?90 days) that compared lurbinectedin against platinum rechallenge (PR) and topotecan (intravenous [TOP-IV] and oral [TOP-oral]) was conducted. Lurbinectedin is a cost-effective second-line treatment for patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy and is under the willingness-to-pay thresholds of $100,000/QALY.
- |||||||||| Irene (pyrotinib) / Jiangsu Hengrui Pharma, Pozenveo (poziotinib) / Spectrum Pharma, Luye Group, Enhertu (fam-trastuzumab deruxtecan-nxki) / Daiichi Sankyo, AstraZeneca
Review, Journal: Targeting HER2 alterations in non-small cell lung cancer: Therapeutic breakthrough and challenges. (Pubmed Central) - Mar 7, 2023
In particular, pyrotinib has shown moderate efficacy as well as a manageable safety profile, and it is now being further evaluated as monotherapy or combined with other existing therapies; by contrast, while poziotinib has demonstrated promising preliminary results, the high rates of toxicity has hampered subsequent studies. Most notably, trastuzumab deruxtecan (T-DXd, DS-8201) has led to a significant breakthrough, with the most encouraging efficacy data (response rate of 55
- |||||||||| Pozenveo (poziotinib) / Assertio
Trial completion date, Trial primary completion date, EGFR exon 20, HER2 exon 20, Metastases: NCI-2017-00831: Poziotinib in EGFR Exon 20 Mutant Advanced NSCLC (clinicaltrials.gov) - Mar 6, 2023
P2, N=116, Active, not recruiting,
Most notably, trastuzumab deruxtecan (T-DXd, DS-8201) has led to a significant breakthrough, with the most encouraging efficacy data (response rate of 55 Trial completion date: Mar 2023 --> Mar 2024 | Trial primary completion date: Mar 2023 --> Mar 2024
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Zepzelca (lurbinectedin) / PharmaMar, Jazz
Enrollment closed, Enrollment change, Combination therapy: LUPER: Lurbinectedin (PM01183) Combined With Pembrolizumab in Small Cell Lung Cancer. (clinicaltrials.gov) - Mar 3, 2023
P1/2, N=28, Active, not recruiting,
Trial completion date: Mar 2023 --> Mar 2024 | Trial primary completion date: Mar 2023 --> Mar 2024 Recruiting --> Active, not recruiting | N=42 --> 28
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
CME/MOC Credit - Facilitating Progress in the Treatment of SCLC: How to Optimize the Use of Current Systemic Options and Accelerate the Clinical Transition of Investigational Approaches by PeerView (Starlight Ballroom) - Feb 19, 2023 - Abstract #IASLCTTLC2023IASLC_TTLC_183;
Notable advances such as chemo-immunotherapy in the first-line setting and lurbinectedin in the second-line setting have now become guideline-recommended standards of care and propelled the treatment of SCLC forward...In this PeerView Live Candid Conversations & Clinical Consults symposium, leading experts will weave together the latest evidence on standard-of-care therapies and the evolving data on new/emerging approaches to provide a big-picture overview of the present and future management of SCLC and how to accelerate further progress in this challenging disease. These discussions will be framed with illustrative patient cases to highlight evidence-based strategies to improve care and outcomes in SCLC.
- |||||||||| Pozenveo (poziotinib) / Assertio
Enrollment closed, Enrollment change, EGFR exon 20, HER2 exon 20, Metastases: NCI-2017-00831: Poziotinib in EGFR Exon 20 Mutant Advanced NSCLC (clinicaltrials.gov) - Feb 17, 2023
P2, N=116, Active, not recruiting,
These discussions will be framed with illustrative patient cases to highlight evidence-based strategies to improve care and outcomes in SCLC. Recruiting --> Active, not recruiting | N=80 --> 116
- |||||||||| Pozenveo (poziotinib) / Assertio, Cyramza (ramucirumab) / Eli Lilly
Enrollment change, Trial completion date, Trial withdrawal, Trial primary completion date, EGFR exon 20, Metastases: Poziotinib and Ramucirumab for the Treatment of EGFR Exon 20 Mutant Stage IV Non-small Cell Lung Cancer (clinicaltrials.gov) - Feb 16, 2023
P2, N=0, Withdrawn,
Recruiting --> Active, not recruiting | N=80 --> 116 N=36 --> 0 | Trial completion date: Dec 2024 --> Feb 2023 | Not yet recruiting --> Withdrawn | Trial primary completion date: Dec 2024 --> Feb 2023
- |||||||||| Zepzelca (lurbinectedin) / PharmaMar, Jazz
Journal: Editorial: Small cell lung cancer: New drugs and strategies. (Pubmed Central) - Feb 14, 2023
N=36 --> 0 | Trial completion date: Dec 2024 --> Feb 2023 | Not yet recruiting --> Withdrawn | Trial primary completion date: Dec 2024 --> Feb 2023 No abstract available
- |||||||||| Pozenveo (poziotinib) / Assertio
Enrollment closed, HER2 exon 20, Metastases: Study of Poziotinib in Japanese Patients With NSCLC (clinicaltrials.gov) - Jan 31, 2023
P1/2, N=76, Active, not recruiting,
Not yet recruiting --> Recruiting Recruiting --> Active, not recruiting
- |||||||||| Pozenveo (poziotinib) / Assertio
Enrollment closed, 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 31, 2023
P2, N=603, Active, not recruiting,
Recruiting --> Active, not recruiting Recruiting --> Active, not recruiting
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