Phase I Clinical Study to Assess Safety and Efficacy of Repotrectinib Combined With Osimertinib in Patients With Advanced, Metastatic EGFR Mutant NSCLC (TOTEM).

This is a Phase I study of repotrectinib in combination with osimertinib in patients with advanced or metastatic EGFR mutant non small cell lung cancer (NSCLC).
The study will be conducted in 2 parts, Part Ia and Part Ib, and its purpose will be to find the incidence of dose-limiting toxicities (DLTs) as defined by the primary safety and tolerability endpoint. The Phase Ia study will also determine the impact of repotrectinib on osimertinib pharmacokinetics (PK) and the maximum tolerated dose (MTD), if reached, of repotrectinib given in combination with osimertinib and the recommended Phase II dose (RP2D). Dose escalation will be conducted according to a 'Rolling-6' based study design with 3 dose levels for repotrectinib: 80 mg once a day (QD), 160 mg QD or 160 mf QD during 14 days followed by 160 mg twice a day (BID); in combination with 80 mg QD of osimertinib. A total of 6 patients will be enrolled in each dose level cohort.
In addition, this Phase Ib study will test early drug activity (efficacy) of the proposed combination treatment in an expansion cohort at the RP2D.

开始日期2022-02-11

申办/合作机构

Instituto Oncológico Dr. Rosell

[+1]

NCT04487756

/ Active, not recruiting临床1/2期IIT

Phase Ib/II Trial of the Combination of Atezolizumab With Dendritic Cell Vaccination as Maintenance Treatment in Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC) After Induction Treatment

This is a single-arm Phase Ib/II multicenter open-label study, with translational sub-study, of atezolizumab plus autologous dendritic cell vaccine as maintenance treatment in extensive-stage small cell lung cancer (ES-SCLC). It is expected that three Spanish sites will include patients in this study.
Patients will receive standard treatment with carboplatin and etoposide, plus atezolizumab for four 21-day cycles (induction phase), followed by a maintenance phase during which they will receive the dendritic cell vaccine (6 doses maximum) in combination with atezolizumab until they had unacceptable toxic effects, disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, or no additional clinical benefit.
The two primary endpoints are the investigator-assessed toxicity and the 6 months PFS, both in the intention-to-treat population. Secondary Outcome Measures include: Duration of clinical benefit (DCB), Overall survival (OS) and Overall response rate (ORR)
The translational substudy will include:
Analysis of tumor tissue samples will consist of PD-L1 Immunohistochemistry testing, RNA expression, Work Environmental Scale (WES) analysis, and flow cytometry in pretreatment fresh tumor tissue.
The analysis will consist of T cell immunophenotyping, DC immunophenotyping, Tumoral RNA analysis by nanostring and tumoral cell-free DNA analysis by WES and cytokine analysis

开始日期2021-03-17

申办/合作机构

Instituto Oncológico Dr. Rosell

[+1]

NCT04537130

/ Unknown status临床1期IIT

Phase Ib Controlled Exploratory Trial for Treatment of Fibrosing Interstitial Lung Disease Patients Secondary to SARS-CoV-2 Infection With IN01 Vaccine (COVINVAC)

Methodology:
This is a controlled, randomized, multicenter open-label Phase Ib clinical exploratory trial in patients with fibrosing interstitial lung disease secondary to SARS-CoV-2 infection.
Patients who give informed consent will be screened for enrolment in the study. Patients that meet the eligibility criteria will be enrolled and randomly allocated in the control arm (best standard of care) or the experimental arm (best standard of care plus IN01 vaccination).
The patients enrolled in the control arm of the study will receive standard of care.
The primary endpoint is safety, measured by the Frequency and severity of AEs graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 criteria. Biochemical and blood count alterations will be also monitored. Safety will be defined based on the frequency and severity of adverse events (AEs) throughout the patient's participation in the study comparing between control and experimental arms.
Efficacy will be measured as function of the annual rate of decline in the Forced Vital Capacity (FVC) at 1 year after patient inclusion in the study and the blood oxygen saturation levels at days 1, 14 (w2), d 28 (w4), 42 (w6) and 92 (w12); week 24, week 36 and week 52. High-resolution Computed Tomography (CT) scans will be taken at at baseline and weeks, 12, 24, and 52 to evaluate the resolution of the fibrosing interstitial lung disease.
A translational substudy will be included.
Objectives:
Primary Objective
● To evaluate the safety and tolerability of IN01 vaccine in diagnosed ex-COVID-19 patients that develop fibrotic lung syndrome after infection.
Secondary Objectives
* To evaluate the effect of IN01 vaccine on Oxygen saturation, pulmonary function, quality of life and fibrosing status in ex-COVID-19 patients that developed fibrosing lung disease after infection.
* To assess biomarkers and molecular markers related to the IN01 vaccine mechanism of action.

开始日期2020-12-01

申办/合作机构

Instituto Oncológico Dr. Rosell

[+2]

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2025-07-01·EClinicalMedicine

Prevention of sacituzumab govitecan-related neutropenia and diarrhea in patients with HER2-negative advanced breast cancer (PRIMED): an open-label, single-arm, phase 2 trial

Article

作者: Morales, Serafin ; Martínez-Bueno, Alejandro ; Rendo, Cristina Reboredo ; González, Xavier ; Guerrero, José Antonio ; Piwowarska, Zuzanna ; Ruiz-Borrego, Manuel ; Shimizu, Eileen ; Cortez, Patricia ; Sampayo-Cordero, Miguel ; Gion, María ; Blanch, Salvador ; Llombart-Cussac, Antonio ; Cortés, Javier ; López-Miranda, Elena ; Blancas, Isabel ; Ancizar, Nerea ; Pérez-García, José Manuel ; Recalde, Sabela

Background:

Neutropenia and diarrhea are common sacituzumab govitecan-related adverse events, frequently leading to treatment modifications. PRIMED evaluated primary prophylactic granulocyte colony-stimulating factor (G-CSF) and loperamide to improve sacituzumab govitecan tolerability.

Methods:

PRIMED (NCT05520723) was an open-label, single-arm, phase II study that enrolled HER2-negative advanced breast cancer patients previously treated with 1-2 chemotherapy regimens for metastatic disease. Patients with hormone receptor positive tumors previously received CDK4/6 inhibitor in the advanced setting. Sacituzumab govitecan was administered until disease progression or unacceptable toxicity. G-CSF (5 MU/kg/day) and loperamide (2 mg/twice a day or 4 mg/day) were given during the first two cycles and at physician's discretion thereafter. Primary endpoints were (i) incidence of grade ≥3 neutropenia and (ii) incidence of grade ≥2 diarrhea, both assessed after two treatment cycles. Secondary endpoints included efficacy and extended safety.

Findings:

Between February 2023 and September 2023, 50 patients were enrolled. At data cut-off, median follow-up was 9.0 months (range, 0.2-13.5). Disease progression was the main reason for treatment discontinuation (33 patients, 66.0%). During the first two cycles, incidence of any grade neutropenia and diarrhea were 28.0% and 34.0%, respectively. Eight patients (16.0%) had ≥ grade 3 neutropenia, meeting this primary endpoint (p = 0.00023). No patients developed febrile neutropenia. Eight patients (16.0%) had ≥ grade 2 diarrhea (4.0% grade 3) (p = 0.084). The rate of adverse events associated with dose reductions and temporary treatment interruptions during the first two cycles was 14.0% and 30.0%, respectively.

Interpretation:

Primary prophylactic administration of G-CSF and loperamide resulted in a clinically relevant reduction of the incidence and severity of sacituzumab govitecan-related neutropenia and diarrhea.

Funding:

Gilead Sciences, S.L.U.

2025-06-01·Clinical Lung Cancer

Tepotinib Plus an EGFR Tyrosine Kinase Inhibitor in Patients With EGFR-Mutant MET-Altered NSCLC: A Case Series

Article

作者: Hsia, Te-Chun ; Lee, Kirsty Wai Chung ; Froesch, Patrizia ; Mazieres, Julien ; Karachaliou, Niki ; Lam, Wei-Sen ; Vlassak, Soetkin ; Raut, Nirmal Vivek ; Petrini, Iacopo ; O'Sullivan, Hazel ; Hochmair, Maximillian J ; Himpe, Ulrike ; Le, Xiuning ; van der Wekken, Anthonie J ; Chan, Oscar Siu Hong ; Farrugia, David ; Chang, Gee-Chen ; Joshi, Kirti ; Tho, Lye Mun ; González-Cao, Maria ; De Bondt, Charlotte ; Samol, Jens ; Ahmad, Azura ; Berghoff, Karin ; Yang, Tsung-Ying ; Hendriks, Lizza ; Eisert, Anna ; Popat, Sanjay

No targeted treatments are currently approved for patients with EGFR-mutant non-small-cell lung cancer (NSCLC) and MET-mediated resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).This case series describes real-world outcomes with tepotinib, a selective MET-TKI, in combination with EGFR-TKIs in patients with EGFR-mutant, MET-altered NSCLC and resistance to EGFR-TKIs.Among the 25 patients included, tepotinib was given in combination with a range of EGFR-TKIs (osimertinib, n = 18; gefitinib, n = 5; dacomitinib, n = 1; afatinib, n = 1) as second (n = 8), third (n = 9), or fourth-or-later (n = 8) line therapy.Tepotinib plus EGFR-TKIs demonstrated clin. benefit per physician′s assessment in 23/25 patients, with a partial response in 15/25 patients.Tepotinib plus EGFR-TKIs showed favorable tolerability that was consistent with previous observations, with edema reported as the most common tepotinib-related adverse event (14/25 patients).This case series, including patients with several prior treatment lines, suggest tepotinib plus an EGFR-TKI as a potential chemotherapy-sparing, oral targeted treatment option for patients with EGFR-mutated, MET-altered NSCLC after progression on EGFR-TKIs.

2025-04-01·CLINICAL CANCER RESEARCH

Elacestrant in Women with Estrogen Receptor–Positive and HER2-Negative Early Breast Cancer: Results from the Preoperative Window-of-Opportunity ELIPSE Trial

Article

作者: Bellet, Meritxell ; Cortadellas, Tomás ; Gonzalez-Farré, Xavier ; Muñoz-Mateu, Montserrat ; Falato, Claudette ; Siso, Christian ; Pascual, Tomás ; Amillano, Kepa ; Bergamino, Milana A. ; Espinosa Guerrero, Alejandra ; Luna, Miguel A. ; Salvador, Fernando ; Cebrecos, Isaac ; Galván, Patricia ; Ferrero-Cafiero, Juan M. ; Sanfeliu, Esther ; Prat, Aleix ; Margelí Vila, Mireia ; Vidal, Maria ; Sanchez-Bayona, Rodrigo ; Pare, Laia

Abstract:

Purpose::

Elacestrant has shown significantly prolonged progression-free survival compared with standard-of-care endocrine therapy in estrogen receptor–positive (ER-positive), HER2-negative metastatic breast cancer, whereas potential benefit in early-stage disease requires further exploration. The SOLTI-ELIPSE window-of-opportunity trial investigated the biological changes induced by a short course of preoperative elacestrant in postmenopausal women with early breast cancer.

Patients and Methods::

Eligible patients with untreated T1c (≥1.5 cm)-T3, N0, ER-positive/HER2-negative breast cancer with locally assessed Ki67 ≥10% received elacestrant at a daily dose of 345 mg for 4 weeks. The primary efficacy endpoint was complete cell cycle arrest, defined as Ki67 ≤2.7%, on day 28.

Results::

Overall, 22 patients were evaluable for the primary endpoint. Elacestrant was associated with a complete cell cycle arrest rate of 27.3% and a statistically significant Ki67 geometric mean change of −52.9% (P = 0.007; 95% confidence interval, −67.4 to −32.1). Notably, the treatment with elacestrant led to a shift toward a more endocrine-sensitive and less proliferative tumor phenotype based on PAM50-based gene signatures. Elacestrant increased the expression of immune-response genes (GZMB, CD4, and CD8A) and suppressed proliferation and estrogen-signaling genes (MKI67, ESR1, and AR). These biological changes were independent of the levels of Ki67 suppression on day 28. The most common adverse events were grade 1 anemia (21.7%), hot flushes (8.7%), constipation (8.7%), and abdominal pain (8.7%). One patient experienced a grade 3 cutaneous rash, leading to treatment discontinuation. No other serious adverse events were reported.

Conclusions::

Preoperative treatment with elacestrant in early breast cancer demonstrated relevant biological and molecular responses and exhibited a manageable safety profile. These findings support further investigation of elacestrant in the early setting.

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