Treatment Resistance Following Anti-cancer Therapies

The TRANSLATE study aims to better understand why tumors become resistant to standard anti-cancer therapies.

New tumor biopsy and blood samples are collected after disease progression on standard-of-care anti-cancer treatment and compared to the initial (archival) tumor biopsy sample taken from the same patient.

Annotated reports of results from clinical Next Generation Sequencing (NGS) gene panel tests of both tumor and blood are sent directly from the testing lab to the study physician for discussion with the patient during the study.

Patients may participate in interventional treatment clinical trials at the same time as participating in the TRANSLATE study.

Primary data will be publicly available after the study to support further research.

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. The TRANSLATE 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.

Eligible Tumor Type and Most Recent SOC Therapy:

• Non-small-cell lung and Anti-PD-1/-L1 monotherapy
• Non-small-cell lung and Anti-PD-1/-L1 + platinum
• Clear cell renal cell carcinoma and Anti-PD-1/-L1 monotherapy
• Clear cell renal cell carcinoma and Doublet anti-PD-1/-L1 + anti-CTLA-4
• Clear cell renal cell carcinoma and Pembrolizumab + axitinib
• Clear cell renal cell carcinoma and Avelumab + axitinib
• HR+ HER2- breast and Palbociclib + hormonal therapy
• germline mutated BRCA breast and Olaparib or talazoparib monotherapy
• Castration-resistant prostate and Enzalutamide
• Castration-resistant prostate and Abiraterone + prednisone

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 post-progression tumor lesion that is safely accessible for a new biopsy.

The results from clinical NGS panel testing may help inform subsequent treatment plan or identification of relevant interventional clinical trials.

Patients are enrolled after disease progression on SOC and before change in treatment and participate in 3 study visits within approximately 3 months.

Next-generation sequencing results from analysis of tumor tissue and blood will be returned to the study physician and patient for review at a subsequent study visit within this timeframe.

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.

Primary data will be publicly available after the study to support further research.

Sponsored by Pfizer Inc.; EudraCT: 2018-003612-45.

• Procedure: De novo tumor tissue biopsy
  De novo tissue biopsy performed following disease progression
• Procedure: Research blood draws
  Blood biospecimens collected following disease progression

Inclusion Criteria:

• Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors treated as follows:
• Non small cell lung carcinoma (NSCLC) monotherapy: Disease progression (PD) on 1st line monotherapy anti PD-1/ L1.
• NSCLC combination: PD on 1st line anti PD-1/ L1 plus standard doublet platinum containing regimen; or PD on 1st-line anti-PD-1/-L1 plus standard doublet platinum-containing regimen followed by continuation of single agent anti-PD-1/-L1).
• Renal cell carcinoma (RCC) with clear cell component: PD on 2nd line monotherapy anti PD-1/ L1; or PD on 1st line combination of doublet anti-PD-1/ L1 with anti-CTLA-4; or PD on 1st-line combination of avelumab with axitinib or pembrolizumab with axitinib.
• HR+ HER2 adenocarcinoma of the breast: PD on 1st line combination of doublet palbociclib with hormonal therapy.
• Castrate resistant adenocarcinoma of the prostate: PD on enzalutamide monotherapy.
• Castrate resistant adenocarcinoma of the prostate: PD on abiraterone in combination with prednisone.
• germline mutated BRCA (gBRCAm), HER2- breast cancer: PD on a PARP inhibitor monotherapy in patients previously treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting.
• Radiographic evidence of PD, including the target lesion being subjected to biopsy for the study, on the most recent regimen that requires a change in anti-cancer treatment.

Exclusion Criteria:

• Tumor biopsy taken from a bone or an irradiated target lesion.
• Discontinuation of current or most recent anti cancer therapy due to toxicity and not progressive disease.
• Initiation of new anti-cancer therapy after disease progression prior to planned biopsy.