Related Experiment Video

Updated: Jan 22, 2026

Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics
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Camonsertib, an ATRi, in Combination with Low-Dose Gemcitabine in Solid Tumors with DNA Damage Response Aberrations:

Ezra Y Rosen1, Timothy A Yap2, Elisa Fontana3

  • 1Early Drug Development and Breast Medicine Services, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|January 21, 2026
PubMed
Abstract

Insights

Combination treatment with camonsertib and gemcitabine showed preliminary activity in advanced solid tumors. Further research is needed to optimize dosing for better tolerability and identify patient subsets benefiting from this DNA damage repair inhibitor combination.

Area of Science:

  • Oncology
  • Pharmacology
  • Genetics

Background:

  • Combination therapy with gemcitabine and camonsertib, a novel ATR inhibitor, was explored for cancer treatment.
  • Preclinical models indicated potential for tumor cell death with this combination.
  • A Phase 1b study (TRESR) was initiated to assess safety and efficacy in patients with advanced solid tumors.

Purpose of the Study:

  • To evaluate the safety and tolerability of combining gemcitabine and camonsertib in patients with advanced solid tumors.
  • To assess the preliminary efficacy of this combination therapy.
  • To identify an optimal dosing regimen for the combination treatment.

Main Methods:

  • Preclinical testing of cell lines and tumor xenografts across various doses and schedules.
  • Phase 1b clinical trial involving 76 patients with DNA damage repair (DDR) gene alterations.
  • Intermittent dosing regimens of camonsertib and de-escalating gemcitabine were administered.

Main Results:

  • Preclinical studies showed tumor regression with low-dose camonsertib and gemcitabine, with good tolerability.
  • Patients experienced synergistic toxicities, primarily myelosuppression, necessitating gemcitabine dose reduction.
  • An intermittent schedule (1 week on/1 week off) improved tolerability and neutrophil recovery, with notable responses in gynecological cancers.

Conclusions:

  • The combination of camonsertib and low-dose gemcitabine demonstrated preliminary clinical activity.
  • Challenging tolerability necessitates further investigation to determine the optimal dosing regimen.
  • Identifying specific patient subsets who benefit most from this combination is crucial for future clinical application.

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