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  • PO003/#269  Ignite: a phase II signal-seeking trial of adavosertib targeting recurrent high grade serous ovarian cancer with cyclin E1 over-expression with and without gene amplification

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Plenary 01: Oral Abstract Presentations
AS11. Ovarian cancer
PO003/#269  Ignite: a phase II signal-seeking trial of adavosertib targeting recurrent high grade serous ovarian cancer with cyclin E1 over-expression with and without gene amplification
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  1. George Au-Yeung1,
  2. Mathias Bressel2,
  3. Owen Prall3,
  4. Petra Opar2,
  5. John Andrews4,
  6. Sally Mongta5,
  7. Yeh Chen Lee6,
  8. Bo Gao7,
  9. Tarek Meniawy8,
  10. Sally Baron-Hay9,
  11. Allison Black10,
  12. Ganessan Kichenadasse11,
  13. Sumitra Ananda12,
  14. Peter Fox13,
  15. David Bowtell14 and
  16. Linda Mileshkin1
  1. 1Peter MacCallum Cancer Centre, Medical Oncology, Melbourne, Australia
  2. 2Peter MacCallum Cancer Centre, Biostatistics and Clinical Trials, Melbourne, Australia
  3. 3Peter MacCallum Cancer Centre, Pathology, Melbourne, Australia
  4. 4Australia New Zealand Gynaecological Oncology Group, Research, Camperdown, Australia
  5. 5Peter MacCallum Cancer Centre, Parkville Cancer Clinical Trials Unit, Melbourne, Australia
  6. 6Royal Hospital for Women, Gynaecologic Oncology Department, Sydney, Australia
  7. 7Westmead and Blacktown Hospital, Medical Oncology, Westmead, Australia
  8. 8Sir Charles Gairdner Hospital, Medical Oncology, Nedlands, Australia
  9. 9Royal North Shore Hospital, Medical Oncology, St Leonards, Australia
  10. 10Royal Hobart Hospital, Medical Oncology, Hobart, Australia
  11. 11Flinders Medical Centre, Medical Oncology, Bedford Park, Australia
  12. 12Sunshine Hospital, Medical Oncology, St Albans, Australia
  13. 13Orange Health Service, Medical Oncology, Orange, Australia
  14. 14Peter MacCallum Cancer Centre, Research Division, Melbourne, Australia

Abstract

Introduction Cyclin E1 amplification and over-expression is associated with platinum resistance in high grade serous ovarian cancer (HGSC), and may predict response to WEE1 inhibition. Adavosertib, a WEE1 inhibitor, has activity in unselected women with recurrent ovarian and endometrial cancer. We aimed to evaluate the efficacy of adavosertib in women with recurrent platinum resistant HGSC (PR-HGSC) with cyclin E1 over-expression, with and without gene amplification.

Methods IGNITE is a multicentre, Phase 2 trial with 2 cohorts of PR-HGSC patients. Cohort 1 were cyclin E1 amplified (≥8 copies by FISH) and over-expressed (H-score>50), and Cohort 2 were non-amplified. Adavosertib 300 mg PO was given daily on days 1–5 and 8–12 q21-day cycle (dose was reduced to 200 mg after n=71 due to safety concerns). The primary endpoint was clinical benefit (CB) defined as no progression for ≥ 18 weeks. Here we present the 18-week CB rate (CBR) and overall response rate (ORR), with data cut-off of Apr-2023.

Results From Jan-2020 to Oct-2022, 80 patients (Cohort 1 n=21; Cohort 2 n=59) were accrued. Median age was 64 years (range 42–84), 83% had ≥2 prior chemotherapy lines. For Cohort 1, ORR=38% and CBR=53%. For Cohort 2, ORR=45% and CBR=48%. Treatment related adverse events occurred in 78 patients (97%). Dose reduction was required in 36 (45%) patients, mostly for neutropenia or diarrhoea. Four patients (5%) died from treatment (sepsis n=3; thrombocytopenia n=1).

View this table:
Abstract PO003/#269 Table 1

Response and clinical benefit (amplified – all patients)

View this table:
Abstract PO003/#269 Table 2

Response and clinical benefit (non-amplified – all patients)

Conclusion/Implications Adavosertib demonstrated activity in biomarker selected patients with PR-HGSC. Study accrual was halted early due to concern regarding rates of myelotoxicity.

https://doi.org/10.1136/ijgc-2023-IGCS.3

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