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. 2025 Oct 20.
doi: 10.1097/COC.0000000000001263. Online ahead of print.

A Phase 2 Trial of Protein Kinase C Iota Inhibition With the Combination of Auranofin and Sirolimus in Patients With Recurrent Ovarian Cancer

Aminah Jatoi  1 , Nathan R Foster  2 , Andrea Wahner Hendrickson  1 , Matthew S Block  1 , S John Weroha  1 , Erik J Asmus  2 , Nicole R Murray  3 , Alan P Fields  3
Affiliations

A Phase 2 Trial of Protein Kinase C Iota Inhibition With the Combination of Auranofin and Sirolimus in Patients With Recurrent Ovarian Cancer

Aminah Jatoi et al. Am J Clin Oncol. .

Abstract

Objectives: This trial served as a proof-of-concept for whether inhibition of protein kinase C iota (PKCι) with auranofin and sirolimus provide antineoplastic effects in patients with recurrent high-grade serous ovarian cancer.

Methods: This drug combination was administered to patients with recurrent high-grade serous ovarian cancer. Dosing was based on unpublished phase 1 data and consisted of auranofin 6 mg and sirolimus 5 mg both orally per day of a 28-day cycle. The primary endpoint was tumor response. Available tumor tissue was assessed for PKCι protein expression by immunohistochemistry (IHC) and PRKCI copy number by fluorescence in-situ hybridization (FISH) after the start of cancer therapy.

Results: Twenty-two patients were enrolled, and 21 were evaluable for all clinical trial endpoints. One patient was unevaluable because she did not receive a full chemotherapy cycle. No tumor responses were seen in the first 21 patients, resulting in early trial termination per a priori trial design. The median progression-free survival was 2.1 months (95% CI: 1.8-3.7). The median overall survival was 4.4 months (95% CI: 2.6-12.5). Fourteen (67%) patients had at least one grade 3 or worse adverse event. Nineteen of 21 evaluable patients had available tumor tissue, which showed the median PKCι copy number averaged per cell of 3 (range: 2 to 7), and PKCι expression (at least 1+) in all.

Conclusions: As prescribed here, auranofin and sirolimus manifested no antineoplastic activity in patients with recurrent high-grade serous ovarian cancer that expressed PKCι.

Trial registration: ClinicalTrials.gov NCT03456700 NCT01737502.

Keywords: auranofin; ovarian cancer; response; sirolimus.

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Conflict of interest statement

AJ is the Betty J. Foust, M.D. and Parents’ Professor of Oncology. APF is the Monica Flynn Jacoby Endowed Professor of Cancer Biology. MSB declares institutional research support from Alkermes, Bristol-Myers Squibb, Genentech, Merck, nFerence, Perspective Therapeutics, Pharmacyclics, Regeneron, Sorrento, TILT Biotherapeutics, and Transgene; is a consultant for Perspective Therapeutics, Sorrento Therapeutics, and TILT Biotherapeutics; and is listed as an inventor on patents filed by Mayo Clinic: “Dendritic Cell-Based Vaccines and Uses Thereof”, and “Combinations of Dendritic Cell-Based Vaccines and Checkpoint Inhibitors.” None of these relationships are related to the research described in this manuscript. The remaining authors declare no conflicts of interest.

References

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    1. Jatoi A, Radecki Breitkopf C, Foster NR, et al. A mixed-methods feasibility trial of protein kinase C iota inhibition with auranofin in asymptomatic ovarian cancer patients. Oncology. 2015;88:208–213.

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