Whole-genome and transcriptome sequencing of patients with advanced solid tumors enrolled in
the NCT/DKTK MASTER (Molecularly Aided Stratification for Tumor Eradication Research) program
revealed genetic alterations in a substantial proportion of patients including (i)
alterations that lead to aberrant activation of BRAF, ERBB2, ALK, and the PI3K-AKT and MAPK
pathways and (ii) changes that predict sensitivity to immune checkpoint inhibition, such as
high tumor mutational burden and specific alterations of the PD-L1 locus.
Within this seven-arm basket phase II clinical trial, we aim to investigate the efficacy of
targeted-therapy plus immune checkpoint inhibition in patients with advanced tumors
exhibiting one of the following genetic alterations detected within the NCT/DKTK MASTER
study: (i) BRAF V600E/K, (ii)ERBB2 amplification and/or overexpression or activating ERBB2
mutation, (iii) ALK rearrangement or activating ALK mutation, (iv) activating PIK3CA or AKT
mutations or other aberration predicting increased PI3K-AKT pathway activity, (v) abberations
predicting increased RAF-MEK-ERK pathway activity; (vi) patients with high tumor mutational
burden and/or specific alteration predicting sensitivity to PD-1/PD-L1 inhibition are
eligible within this study for immune checkpoint inhibition. Recruitment of adequate patient
numbers into these well-defined molecular subgroup is achieved in a multicenter approach
including NCT Heidelberg and NCT Dresden as well as DKTK partner sites. Eligible patients
will be identified by in-depth molecular characterization of tumors within the NCT/DKTK
MASTER program. All study arms are based on similar biometrical assumptions, and sample size
as well as power calculations are based on Simon's optimal two-stage design for each study
arm separately. The overall aim is to reduce the cumulative hazard of progression-free
survival observed within the study (PFS2) compared to the cumulative hazard of the
progression-free time before inclusion into the study (PFS1) using a paired log-rank test.
The sample size of the entire trial varies according to the performance of the individual
study arms, ranging between 98 and 175 patients.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.