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Updated: Jan 21, 2026

Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel
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A phase I study of AT-101, a BH3 mimetic, in combination with paclitaxel and carboplatin in solid tumors

Mark N Stein1,2,3, Susan Goodin4,5, Murugeson Gounder4,5

  • 1Department of Medicine, Robert Wood Johnson Medical School, New Brunswick, NJ, 08903, USA. mns2146@cumc.columbia.edu.

Investigational New Drugs
|August 8, 2019
PubMed

Insights

The combination of AT-101 with paclitaxel and carboplatin showed moderate toxicity in advanced solid tumors. Clinical efficacy was modest, and this combination will not be further investigated.

Area of Science:

  • Oncology
  • Pharmacology
  • Clinical Trials

Background:

  • AT-101 is a BH3 mimetic targeting anti-apoptotic proteins like Bcl-2.
  • It aims to lower the threshold for apoptosis by inhibiting protein heterodimerization.
  • This study explores its use in advanced solid tumors.

Purpose of the Study:

  • Investigate the maximum tolerated dose (MTD) of AT-101 combined with paclitaxel and carboplatin.
  • Characterize the toxicity, efficacy, pharmacokinetics, and pharmacodynamics of this combination therapy.
  • Evaluate the potential of this combination in treating advanced solid tumors.

Main Methods:

  • A phase I clinical trial was conducted with patients receiving AT-101 (40 mg q12h on days 1-3) plus escalating doses of paclitaxel and carboplatin.
  • Two dose levels (DL1 and DL2) were evaluated, with dose-limiting toxicities (DLTs) monitored.
  • Secondary objectives included pharmacokinetic and pharmacodynamic assessments.

Main Results:

  • Twenty-four patients were enrolled; prostate cancer was the most common diagnosis (N=11).
  • Two DLTs were observed (grade 3 abdominal pain, grade 3 ALT increase), but the MTD was not determined.
  • One complete response (esophageal cancer) and four partial responses (1 NSCLC, 3 prostate) were recorded; pharmacodynamic studies showed no significant changes in target proteins or apoptosis.

Conclusions:

  • The combination of AT-101, paclitaxel, and carboplatin was found to be safe and tolerable in patients with advanced solid tumors.
  • Due to modest clinical efficacy observed in this phase I trial, further investigation of this specific combination is not planned.
  • The study provides safety and preliminary efficacy data for this novel combination therapy.
Keywords:
ApoptosisBCL-2ChemotherapyPhase IProstate

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