Abstract 1976TiP
Background
Development of new cancer treatments requires better understanding of why tumors develop resistance to standard-of-care (SOC) therapies. However, post-progression tumor biopsies are not routinely collected, limiting the tissue available to characterize mechanisms of treatment resistance. This translational clinical study is specifically designed to address these critical gaps.
Trial design
TRANSLATE is a global, multicenter, translational study designed to collect and compare archival pre-treatment tumor tissue with paired de novo tumor and blood samples obtained following disease progression on SOC therapies, targeting therapeutically important areas of cancer biology (Table). Eligibility criteria include adults with locally advanced or metastatic tumors; radiographic evidence of progressive disease during the most recent SOC regimen; sufficient archival tumor tissue; and a safely accessible de novo post-progression tumor biopsy site. Patients are permitted to participate in interventional treatment clinical trials at the same time as participating in this study, with prior sponsor agreement. Patients are enrolled after disease progression on SOC and before change in treatment. Next-generation sequencing results from analysis of tumor tissue and blood are returned to the study physician and patient for review at a subsequent study visit. The primary endpoint is the change in frequency of gene alterations between pre-treatment and post-progression tumor biopsies. Secondary endpoints address prioritized scientific hypotheses specific to each target area of biology and indication. Clinical study data will be made available to the research community. Status: enrolling patients. Table: 1976TiP
Target biology & disease cohorts
| Inhibitor target | Eligible tumor type | Most recent therapy | Indication | Cohort |
| Immune checkpoint | ||||
| Non-small cell lung | Anti-PD-1/-L1 monotherapy | 1st line | 1 | |
| Anti-PD-1/-L1 + platinum | 1st line | 2 | ||
| Clear cell renal cell carcinoma | Anti-PD-1-L1 monotherapy or | 2nd line | 3 | |
| Doublet anti-PD-1/-L1 + anti–CTLA-4 or | 1st line | |||
| Pembrolizumab + axitinib or avelumab + axitinib | 1st line | |||
| CDK4/6 | ||||
| HR+ HER2– breast | Palbociclib + hormonal therapy | 1st line | 4 | |
| Androgen receptor | ||||
| Castration-resistant prostate | Enzalutamide | Any line | 5 | |
| Abiraterone + prednisone | Any line | 6 | ||
| PARP | ||||
| gBRCAm breast | Olaparib or talazoparib monotherapy | gBRCAm, HER2– | 7 |
CDK, cyclin-dependent kinase; gBRCAm, germline mutated BRCA
Clinical trial identification
EudraCT: 2018-003612-45; NCT04436120.
Editorial acknowledgement
Medical writing support was provided by Ben Scott, PhD, of Scott Medical Communications, CMC AFFINITY, and McCann Health Medical Communications, and was funded by Pfizer.
Legal entity responsible for the study
Pfizer Inc.
Funding
Pfizer Inc.
Disclosure
C. Helissey: Advisory/Consultancy: Roche; Advisory/Consultancy: Janssen; Advisory/Consultancy: Astellas; Advisory/Consultancy: Sanofi; Advisory/Consultancy: AstraZeneca. J-F. Martini, A. Thall, N. Cossons, S. Ho: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer Inc. All other authors have declared no conflicts of interest.