pegylated liposomal doxorubicin

Two hundred sixty-six patients were randomly assigned 2:1 to olaparib tablets (300 mg twice daily; n = 178) or physician's choice of single-agent nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan; n = 88). BRCA reversion mutations might have contributed to this finding. No patient randomly assigned to olaparib with a BRCA reversion mutation detected at baseline (6 of 170 [3.5%]) achieved an objective tumor response.

P2, N=28, Recruiting, University of Colorado, Denver | Trial completion date: Nov 2025 --> Nov 2026 | Trial primary completion date: Nov 2024 --> Nov 2025

P=N/A, N=24, Active, not recruiting, Fox Chase Cancer Center | Trial completion date: Oct 2024 --> Oct 2027 | Trial primary completion date: Jun 2021 --> Oct 2026

P2/3, N=260, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Oct 2025

P1, N=12, Terminated, Swiss Group for Clinical Cancer Research | N=30 --> 12 | Trial completion date: Oct 2024 --> Dec 2023 | Recruiting --> Terminated; The premature termination is based on the unexpectedly low patient accrual to the clinical trial and the strategic considerations in the development of the TLD-1 after having included 13 out of 14 patients in the comparative PK part.

P2, N=90, Active, not recruiting, Bristol-Myers Squibb | Recruiting --> Active, not recruiting

P1/2, N=10, Terminated, Pfizer | Phase classification: P2 --> P1/2

P3, N=453, Completed, ImmunoGen, Inc. | Active, not recruiting --> Completed

P2, N=49, Not yet recruiting, Fudan University

P3, N=340, Active, not recruiting, Merck Sharp & Dohme LLC | N=800 --> 340 | Trial completion date: Jul 2028 --> Mar 2025 | Trial primary completion date: Jul 2028 --> Mar 2025

P2, N=10, Terminated, Pfizer | Phase classification: P1/2 --> P2

P2/3, N=650, Active, not recruiting, Daiichi Sankyo | Recruiting --> Active, not recruiting

P2, N=136, Active, not recruiting, AGO Research GmbH | Recruiting --> Active, not recruiting

P1, N=47, Completed, Gustave Roussy, Cancer Campus, Grand Paris | Active, not recruiting --> Completed

P1, N=24, Recruiting, Case Comprehensive Cancer Center | Trial completion date: Nov 2024 --> Apr 2025 | Trial primary completion date: Oct 2024 --> Apr 2025

P2, N=120, Recruiting, Université de Sherbrooke | Initiation date: Sep 2024 --> Dec 2024

P2, N=38, Not yet recruiting, OHSU Knight Cancer Institute

P1, N=86, Active, not recruiting, Shattuck Labs, Inc. | Trial completion date: Apr 2025 --> Nov 2024

P3, N=530, Not yet recruiting, Genmab

For patients with pCR, the differences in EFS (log-rank p = 0.47) and OS (log-rank p = 0.38) were not statistically significant among the three groups, and the EFS (log-rank p = 0.59) and OS (log-rank p = 0.14) of non-pCR patients in the PLD group were similar to those in the epirubicin and pirarubicin groups. PLD had a similar therapeutic response and prognosis compared to epirubicin or pirarubicin in NAC for patients with HR ⩽ 10%/HER2 negative breast cancer, which means that PLD represents a potential NAC option.

P2, N=252, Recruiting, Guangdong Provincial People's Hospital | Initiation date: Jan 2024 --> Sep 2024

P3, N=579, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2024 --> Aug 2025

P3, N=417, Completed, Grupo Español de Investigación en Cáncer de Ovario | Trial completion date: Jan 2024 --> Aug 2024 | Trial primary completion date: Jan 2024 --> Aug 2024 | Active, not recruiting --> Completed

P2/3, N=600, Recruiting, Sutro Biopharma, Inc. | Trial completion date: Feb 2026 --> Feb 2028 | Trial primary completion date: Sep 2025 --> Aug 2027

P2, N=31, Recruiting, Haider Mahdi | Trial completion date: Dec 2027 --> Dec 2031 | Trial primary completion date: Sep 2025 --> Sep 2029

P2, N=120, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2025 --> Jun 2025

P1, N=86, Active, not recruiting, Shattuck Labs, Inc. | Trial primary completion date: Jul 2024 --> Dec 2024

P2, N=90, Recruiting, Celgene | Not yet recruiting --> Recruiting

P2, N=31, Not yet recruiting, Roswell Park Cancer Institute | Trial completion date: Jun 2028 --> Sep 2028 | Initiation date: Jun 2024 --> Sep 2024 | Trial primary completion date: Jun 2028 --> Sep 2028

P3, N=453, Active, not recruiting, ImmunoGen, Inc. | Trial completion date: Apr 2024 --> Aug 2024

P1, N=36, Completed, Baxter Healthcare Corporation | Not yet recruiting --> Completed

Here, we report updated nonanalytical results based on a median follow-up of 16.7 months. 453 PROC pts with high FRα expression (VENTANA FOLR1 [FOLR1-2.1] RxDx Assay) with 1-3 prior therapies were randomized 1:1 to MIRV 6 mg/kg, adjusted ideal body weight, Day 1 of a 21-day cycle or ICC: paclitaxel (PAC), pegylated liposomal doxorubicin (PLD), or topotecan (Topo). With a median follow-up of 16.7 months, MIRV demonstrated improved efficacy vs ICC in pts with PROC. The efficacy data, along with the well-characterized safety profile, supports MIRV as the standard of care for pts with FRα positive PROC. Clinical Trial Information: NCT04209855.

Comparable efficacy and safety between adjuvant PLD and epirubicin for stage I-II HER2-negative breast cancer was observed. There was no difference in 5-year DFS and OS rate between the two treatment arms. However, less grade 3-4 AEs and a trend of favorable QoL symptom scales were observed in the LC arm, suggesting that PLD-containing regimen could become a new standard treatment for early stage HER2-negative breast cancer patients.

P2/3, N=156, Completed, Southwest Hospital, Army Medical University; Southwest Hospital, Army Medical University | Not yet recruiting --> Completed

Three dose levels of PLD (Duomeisu®) were studied (30, 40, or 50 mg/m2) in combination with cyclophosphamide (1500 mg/m2), mesna (1500 mg/m2), and vincristine (1.5 mg/m2, maximum 2 mg) once every 3 weeks. 82203303], and the Basic and Applied Basic Research Foundation of Guangdong Province [No. 2021A1515110234].

P2/3, N=587, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2024 --> Jun 2025

The distribution and accumulation of commercial pegylated liposomal doxorubicin (PLD) and PD-L1 antibody (anti-PD-L1) in the tumor were analyzed through frozen section analysis, ELISA, and in vivo fluorescence imaging...By incorporating US irradiation, the therapeutic efficacy of PLD and anti-PD-L1 was substantially boosted, leading to effective suppression of tumor growth and prolonged survival in mice. The application of US (0.8 W/cm2 for 10 min) can effectively induce vasodilation and enhance the delivery of PLD and anti-PD-L1 into tumors, thereby reshaping the immunosuppressive tumor microenvironment and optimizing therapeutic outcomes.

These findings suggest that liposomal formulations achieve therapeutic benefits through mechanisms that extend beyond the enhanced permeability and retention effect.

Unfortunately, PEGylated liposomal doxorubicin (sLip/DOX) exhibits serious dose-limiting cutaneous toxicities, which are closely related to the extravascular accumulation of sLip/DOX in the dermis...Furthermore, inhibition of complement activation either by CRIg-L-FH (a C3b/iC3b targeted complement inhibitor) or blocking the phosphate negative charge in mPEG-DSPE could significantly reduce liposome uptake by neutrophils and alleviate the cutaneous accumulation of liposomes. These results validated the liposome extravasation pathway mediated by neutrophils and provided potential solutions to the devastating cutaneous toxicities occurring during sLip/DOX treatment.

P=N/A, N=24, Active, not recruiting, Fox Chase Cancer Center | Trial completion date: May 2024 --> Oct 2024

Collectively, our findings provide evidence that ketotifen-induced TME reprograming can improve the efficacy of nanomedicine-based chemoimmunotherapy in sarcomas.

P3, N=456, Active, not recruiting, Mural Oncology, Inc | Recruiting --> Active, not recruiting