CDx Clinical Trials: An Innovative Biomarker‑Driven Design to Select Patient Population Upfront
Innovative phase Ib biomarker driven selection design to select patient population upfront based on their sensitivity to a drug may help to lower the high attrition rate of new drugs.

Vivia Biotech has published the results of new indications for a novel Otsuka drug in the context of a phase Ib clinical trial https://www.spandidos-publications.com/10.3892/mi.2022.32. We use an innovative biomarker‑driven design to select the patient population upfront based on their sensitivity to a drug in a phase Ib clinical trial. This innovative phase Ib biomarker selection design may help to lower the high attrition rate of new drugs.
Vivia Biotech has developed a precision medicine (PM) ex vivo test with 92% patients predicted to be sensitive and 75% overall survival at 3 years with a backbone first line treatment in AML patients.
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A CDx clinical trial selecting patients with this ex vivo PM test would achieve 92% CR and 3-fold increase in overall survival. This is substantially higher than any AML treatment today.
Using this predicted ex vivo PM test, we have analyzed a novel Otsuka drug as CDx clinical trial. This drug was previously studied in a phase I clinical trial with 145 patients diagnosed of a great variety of cancers, but with only one response.
Vivia Biotech preliminary preclinical phase history…
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Vivia discovered that the drug was more active against proliferative cells (blue, leftward curves) than non-proliferative cell (grey, rightwards curves)

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Population Models estimate high interpatient variability and suggest a PM test as CDx could improve clinical response

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Drug is more active than Decitabine as antiproliferative agent. Decitabine is an approved drug for AML. Thus, we expect activity in AML and proposed a clinical trial.

Vivia Biotech CDx Phase Ib clinical trial…

A biomarker-driven design was used in a phase Ib clinical trial for the upfront identification and enrollment of AML patients based on the highest sensitivity to the Otsuka drug, discarding those hypothetically resistant ones and thus minimizing the likelihood of treatment failures.
Pharmacological profile at 72 h of patients with AML included in the clinical trial.
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Dose response curves of OBP-111077 drug in patient samples show those clinically sensitive (green curves) and resistant (red curves) treated patients. Dotted green lines shows the ex vivo sensitive patients who had partial response later, and the dotted red lines reflects the ex vivo less sensitive patients who had treatment failure.
Six patients (50%) were evaluable for clinical efficacy, with 3 out of 6 partial responses, which represents a substantial improvement vs initial phase I clinical trial (1 in 145 patients)

Highlights

  • Vivia Biotech is a key enabler for drug and biomarker discovery & development.
  • Vivia Biotech has profound experience & understanding drug activity in patient samples
  • 2000: Pioneers screening compounds by automated flow cytometry
  • 2007: Pioneers assessing compound activity in patient samples of hematological malignancies by flow cytometry
  • More than 500 drugs & 6.000 samples tested
  • Substantial increase of drug efficacy
  • Proprietary technology, know-how, Native Environment and IO assays
  • Align Drug Discovery & Development & Clinical with horizontal platform
  • From flow cytometry to NGS panels
  • Demonstrated capacity to deliver > 80% correlation with treatment outcome translated into clinical CDx
  • Phase Ib selecting patients with unvalidated CDx
  • The innovative phase Ib biomarker selection design may help to lower the high attrition rate of new drugs
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