Saruparib (AZD5305) Plus Camizestrant Compared With CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant in HR-Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH Non-amplified), BRCA1, BRCA2, or PALB2m Advanced Breast Cancer

Launched by ASTRAZENECA · Apr 18, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new combination treatment for patients with advanced breast cancer that is hormone receptor-positive and HER2-negative. The researchers want to see if the drug saruparib (AZD5305) combined with camizestrant works better than a standard treatment, which includes a CDK4/6 inhibitor along with endocrine therapy. The focus is on patients who have specific genetic mutations (BRCA1, BRCA2, or PALB2) and advanced disease that can't be treated with surgery.

To join the trial, participants need to be adults with a confirmed diagnosis of advanced breast cancer and have the required genetic mutations. They should be in good health overall, without severe complications from other conditions. Those who enroll can expect to receive either the new treatment or the standard treatment and will be monitored closely to see how well they respond. This trial is currently looking for participants of all genders between the ages of 65 and 74. It’s important to talk to a doctor about any previous treatments or medical conditions that could affect eligibility.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Adult females, pre/peri-menopausal and/or post-menopausal, and adult males
• • Histologically or cytologically documented diagnosis of HR-positive, HER2-negative breast cancer
• • Advanced breast cancer with either locally advanced disease not amenable to curative treatment or metastatic disease
• • ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks
• • FFPE tumour tissue from each participant
• • Documented germline tumour loss of function mutation in BRCA1, BRCA2, or PALB2
• • Adequate organ and marrow function
• Exclusion Criteria:
• • Participants with history of MDS/AML or with features suggestive of MDS/AML
• • Participants with any known predisposition to bleeding
• • Any history of persisting severe cytopenia
• • Any evidence of severe or uncontrolled systemic diseases or active uncontrolled infections
• • Refractory nausea and vomiting, chronic GI disease, inability to swallow the formulated product, or previous significant bowel resection
• • History of another primary malignancy
• • Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anti-cancer therapy excluding alopecia
• • Spinal cord compression, brain metastases, carcinomatous meningitis, or leptomeningeal disease
• • Evidence of active and uncontrolled hepatitis B and/or hepatitis C
• • Evidence of active and uncontrolled HIV infection
• • Active tuberculosis infection
• • Cardiac criteria, including history of arrythmia and cardiovascular disease
• • Concurrent exogenous reproductive hormone therapy or non-topical hormonal therapy for non-cancer-related conditions
• • Major surgical procedure or significant traumatic injury within 4 weeks of the first dose of study intervention or an anticipated need for major surgery during the study
• • Palliative radiotherapy with a limited field of radiation within 2 weeks or with wide field of radiation or to more than 30% of the bone marrow within 4 weeks before the first dose of study treatment
• • Prior treatment with systemic anti-cancer therapy for locoregionally recurrent or metastatic disease is not permitted, apart from treatment with ET up to 28 days before randomisation
• • Prior treatment within 28 days with blood product support or growth factor support
• • Any systemic concurrent anti-cancer treatment
• * Concomitant use of the following types of medications or herbal supplements within 21 days or at least 5 half-lives of randomisation:
• • 1. Strong and moderate CYP3A4 inducers/inhibitors
• • 2. Sensitive CYP2B6 substrates
• • 3. Substrates of CYP2C9 and/or CYP2C19 which have a narrow therapeutic index, eg, warfarin (and other coumarin-derived vitamin K antagonist anticoagulants) and phenytoin.
• • Concomitant use of drugs that are known to prolong QT and have a known risk of TdP
• • Systemic use of atropine
• * The following exclusion criteria apply to treatments administered for early breast cancer:
• • 1. Disease progression ≤ 84 days following the last dose of neo-adjuvant or adjuvant chemotherapy
• • 2. Disease progression ≤ 1 year (365 days) from the last dose of treatment with a PARPi and/or platinum agent for early breast cancer
• • 3. Disease progression ≤ 1 year (365 days) from the last dose with a CDK4/6i in the adjuvant setting
• • 4. Disease progression ≤ 1 year (365 days) from the last dose of an oral SERD including camizestrant.