Instituto Oncológico Dr. Rosell

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.

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

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.