topotecan

P3, N=705, Recruiting, PharmaMar | Trial completion date: Jun 2025 --> Apr 2026 | Trial primary completion date: Jun 2025 --> Apr 2026

P3, N=440, Not yet recruiting, Suzhou Suncadia Biopharmaceuticals Co., Ltd.

P3, N=478, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

P3, N=448, Recruiting, Mural Oncology, Inc | Active, not recruiting --> Recruiting | Trial completion date: Dec 2026 --> May 2027 | Trial primary completion date: Dec 2025 --> May 2026

P3, N=468, Not yet recruiting, Daiichi Sankyo | Trial completion date: Jan 2028 --> Feb 2029 | Trial primary completion date: Jul 2026 --> Apr 2027

Moreover, marein can significantly sensitize the ABCG2-expressing tumor cells to chemotherapeutic drugs such as topotecan, mitoxantrone, and Olaparib. This study reveals a novel role and mechanism of marein in modulating drug resistance, and may have important implications in treatment of cancers that are resistant to chemotherapeutic drugs that belong to the substrates of ABCG2 transporters.

Trilaciclib is a first-in-class, intravenous cyclin-dependent kinase 4 and 6 inhibitor approved for reducing the incidence of chemotherapy-induced myelosuppression in adult patients with extensive-stage small cell lung cancer receiving a platinum/etoposide-containing or topotecan-containing regimen. Ad hoc analysis using National Cancer Institute classification showed similar results. The US Food and Drug Administration-approved trilaciclib dose of 240 mg/m2 should be reduced by ∼30%, to 170 mg/m2, for patients with moderate or severe HI.

P2, N=42, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Sep 2024

Patients were allocated to 3 arms; Arm 1, BVAC-C injection at 0, 4, 8 weeks; Arm 2, BVAC-C injection at 0, 4, 8, 12 weeks; Arm 3, BVAC-C injection at 0, 4, 8, 12 weeks with topotecan at 2, 6, 10, 14 weeks. Further studies are needed to identify potential biomarkers of response. ClinicalTrials.gov, identifier NCT02866006.

P2/3, N=600, Recruiting, Sutro Biopharma, Inc. | Phase classification: P2 --> P2/3 | N=140 --> 600

P2, N=25, Active, not recruiting, National Cancer Institute (NCI) | N=60 --> 25 | Trial completion date: Jun 2023 --> Dec 2024

P1/2, N=38, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting | N=183 --> 38

P2/3, N=650, Recruiting, Daiichi Sankyo | Not yet recruiting --> Recruiting

Furthermore, we demonstrated that the multicellular architecture altered cancer cell response to chemotherapeutic agents: the inhibition of sphere formation by topotecan was 74.92 ± 4.56 % for PC3 spheres and 45.95 ± 7.84 % for CSS spheres (p < 0.01), docetaxel showed 37,51± 20,88 % and 15,67± 14,08 % inhibition, respectively (p < 0.05). Thus, CSS present an effective in vitro model for examining the extracellular matrix composition and cell-to-cell interactions within the tumor, as well as for evaluating the antitumor activity of drugs.

P1, N=25, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024

P3, N=200, Active, not recruiting, Hospital JP Garrahan | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2023 --> Dec 2024

We find that ZNF827 accumulates at stalled forks and DNA damage sites, where it activates ATR and promotes the engagement of homologous recombination-mediated DNA repair. Additionally, we demonstrate that ZNF827 depletion inhibits replication initiation and sensitizes cancer cells to the topoisomerase inhibitor topotecan, revealing ZNF827 as a therapeutic target within the DNA damage response pathway.

P3, N=686, Recruiting, Luye Pharma Group Ltd. | Not yet recruiting --> Recruiting

P3, N=376, Active, not recruiting, Mural Oncology, Inc | Recruiting --> Active, not recruiting

P1, N=12, Active, not recruiting, National Cancer Institute (NCI)

As single agent, M1774 suppressed cancer cell viability at nanomolar concentrations, showing greater activity than ceralasertib and berzosertib, but less potency than gartisertib and elimusertib in the small-cell lung cancer H146, H82, and DMS114 cell lines. Low dose of M1774 was found highly synergistic with a broad spectrum of clinical DDAs including TOP1 inhibitors (SN-38/irinotecan, topotecan, exatecan, and exatecan), the TOP2 inhibitor etoposide, cisplatin, the RNA polymerase II inhibitor lurbinectedin, and the PARP inhibitor talazoparib in various models including cancer cell lines, patient-derived organoids, and mouse xenograft models. Furthermore, we demonstrate that M1774 reverses chemoresistance to anticancer DDAs in cancer cells lacking SLFN11 expression, suggesting that SLFN11 can be utilized for patient selection in upcoming clinical trials.

Cohort 1 enrolled patients with relapsed SCLC across Arms A (bintrafusp alfa 2400 mg q3 wks), B (bintrafusp alfa 2400 mg on D1 plus topotecan 1 mg/m2/day on D1-5 q3 wks), and C (bintrafusp alfa 1200 mg on D1 q2 wks plus temozolomide 200 mg/m2/day on D1-5 q4 wks). Concomitant TGF-beta and PD-L1 blockade is associated with a high frequency of HPD in SCLC patients. cfDNA could be critical for monitoring HPD. Tumor and blood immune signatures may inform the likelihood of HPD, with immune excluded tumors more likely to develop HPD.NCT Number: NCT03554473Bintrafusp alfa was provided by EMD Serono (CrossRef Funder ID: 10.13039/100004755)

The study suggests that the application of novel BET PROTACs in combination with chemotherapeutics could represent a new therapeutic option to improve the therapy of osteosarcomas. First orally available PROTACs have reached clinical trials.

P3, N=107, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: Jan 2024 --> Jan 2025

P1/2, N=128, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | N=184 --> 128

Each model was tested in vivo against three clinical regimens: cisplatin plus etoposide, olaparib plus temozolomide, and topotecan. Genomic and transcriptional profiles of the full PDX panel revealed that MYC paralog amplifications on ecDNAs were recurrent in relapsed cross-resistant SCLC, and this was corroborated in tumor biopsies from relapsed patients. We conclude that ecDNAs with MYC paralogs are recurrent drivers of cross-resistance in SCLC.

P1/2, N=184, Recruiting, Pfizer | Trial primary completion date: Feb 2024 --> Aug 2024 | Phase classification: P2 --> P1/2

P3, N=490, Recruiting, Amgen | N=700 --> 490 | Trial primary completion date: Sep 2025 --> Aug 2027

P1, N=96, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Feb 2025

P1, N=65, Active, not recruiting, New Approaches to Neuroblastoma Therapy Consortium | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=30, Active, not recruiting, New Approaches to Neuroblastoma Therapy Consortium | Trial completion date: Dec 2023 --> Dec 2024

P1, N=18, Active, not recruiting, New Approaches to Neuroblastoma Therapy Consortium | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1/2, N=80, Recruiting, National Cancer Institute (NCI) | Phase classification: P2 --> P1/2 | Trial primary completion date: Jan 2024 --> Jan 2025

Trabectedin did not improve median OS and showed a worse safety profile in comparison with physician's choice control chemotherapy.

P1, N=44, Recruiting, Boehringer Ingelheim | Not yet recruiting --> Recruiting

Further, Sp1 knockdown or inhibition suppresses GSDME expression, thus reducing chemotherapy drugs (topotecan, etoposide, doxorubicin, sorafinib and cisplatin) induced cell pyroptosis. The regulation process synergizes with STAT3 (Signal transducer and activator of transcription 3) activity and antagonizes with DNA methylation but barely affects GSDMD-mediated pyroptosis or TNF-induced necroptosis. Our current finding reveals a new regulating mechanism of GSDME expression, which may be a viable target for the intervention of GSDME-dependent inflammatory diseases and cancer therapy.

This study, for the first time, furnishes compelling evidence that MA and TPT synergistically reduce cellular proliferation and induce apoptosis in SCLC cells. Combinations of these drugs holds promise as a potential therapeutic strategy to improve efficacy and reduce the side effects associated with TPT.

P2, N=153, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: Dec 2023 --> Dec 2024

P2, N=81, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2023 --> Jan 2025

P3, N=468, Not yet recruiting, Daiichi Sankyo, Inc.

P3, N=421, Active, not recruiting, Jiangsu Simcere Pharmaceutical Co., Ltd. | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Dec 2024

P2, N=149, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Jan 2025 | Trial primary completion date: Dec 2023 --> Jan 2023