PHOENIX DDR/Anti-PD-L1 Trial: A Pre-surgical Window of Opportunity and Post-surgical Adjuvant Biomarker Study of DNA Damage Response Inhibition With or Without Anti-PD-L1 Immunotherapy in Patients With Neoadjuvant Treatment Resistant Residual Triple Negative Breast Cancer

Sponsor
Institute of Cancer Research, United Kingdom
Study ID
NCT03740893
Phase
PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • AZD6738 — DRUG
    PART 1: Pre-operative exposure of 160mg AZD6738 to be administered orally twice daily on Days 5 -14 of the WOP. PART 2: 12 months post-operative exposure to 160mg AZD6738 to be administered orally twice daily on Days 1 - 14 of a 28 day cycle. AZD6738 was removed as intervention under investigation as of 06 August 2024 (due to formal closure of cohort B)
  • Olaparib — DRUG
    PART 1 (cohort C, and cohorts E-G): Pre-operative exposure to 300mg of olaparib to be administered orally twice daily on Days 1-14 of the WOP. PART 2 (cohort C, and cohorts F and G): 12 months post-operative exposure to 300mg olaparib (2 x 150mg tablets) to be administered orally twice daily on a continuous schedule Day 1-28 of a 28 day cycle. Cohort C was formally closed to recruitment since 06 August 2024.
  • Durvalumab — DRUG
    PART 1 (cohort D): Pre-operative exposure to 1500mg durvalumab to be administered via intravenous (IV) infusion on Day 1 only of the WOP. PART 2 (cohorts A and D, and cohorts F and G): 12 months post-operative exposure to 1500mg durvalumab to be administered via intravenous (IV) infusion on Day 1 only of a 28 day cycle. Cohorts A and D were formally closed to recruitment since 06 August 2024.

Study Details

PHOENIX is a window of opportunity (WOP), open-label, multi-centre, phase IIa trial comprising multiple non-comparative treatment cohorts with patient allocation via minimisation (cohorts A-D) or allocation according to HRD and germline BRCA1/2 mutation status (cohorts E-G). The trial consists of two parts: a post-neoadjuvant treatment preoperative WOP component (PART 1); and a post-operative component (PART 2). Cohorts A-D: To assess whether short exposure to a DDR inhibitor or anti-PD-L1 immunotherapy in a preoperative WOP in patients with post-NACT high risk residual disease, generates a signal of anti-tumour biological activity within residual disease tissue. Cohort E: To assess whether short exposure to a DDR inhibitor with or without anti-PD-1 immunotherapy in a preoperative WOP in patients with non-HRD associated TNBC and post-neoadjuvant treatment high risk residual disease, generates a signal of anti-tumour biological activity within residual disease tissue. Cohorts F \& G: To assess whether short exposure to the DDR inhibitor olaparib with or without anti-PD-1 immunotherapy in a preoperative WOP in patients with HRD associated TNBC and post-neoadjuvant treatment high risk residual disease, generates a signal of anti-tumour biological activity within residual disease tissue.

Key Dates

Start date
Oct 15, 2019
Status verified
Aug 2025
Primary completion
Dec 31, 2026
Completion
Jun 30, 2029

Study Design

Enrollment
119 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER

Arms

  • No Intervention: Cohort A (standard care reference cohort)
    Arm formally closed to recruitment since 06 August 2024
  • Experimental: Cohort B (AZD6738 monotherapy)
    Arm formally closed to recruitment since 06 August 2024
  • Experimental: Cohort C (olaparib monotherapy)
    Arm formally closed to recruitment since 06 August 2024
  • Experimental: Cohort D (durvalumab monotherapy)
    Arm formally closed to recruitment since 06 August 2024
  • Experimental: Cohort E: non-HRD and gBRCA1gBRCA1/2 wildtype confirmed at HRD screening
  • Experimental: Cohort F: gBRCA1/2 mutation confirmed at HRD screening
  • Experimental: Cohort G: HRD & gBRCA1/2 wildtype confirmed at HRD screening

Primary Outcome Measure

Cohorts B and C co-primary endpoint #1: Change in mean proliferation index (as measured by tumour cell Ki67 staining) post WOP intervention within post-treatment biopsy compared to pre-treatment baseline biopsy. [ Time Frame: Post 2 weeks of trial treatment in the window of opportunity ]

Central Contacts

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