PAveMenT: Phase Ib Study of Palbociclib and Avelumab in Metastatic AR+ Triple Negative Breast Cancer

Plain English Summary

PAveMenT: Palbociclib and Avelumab in Metastatic AR+ Triple Negative Breast Cancer is a Phase 1 clinical trial sponsored by Royal Marsden NHS Foundation Trust studying Triple Negative Breast Cancer, Locally Advanced Breast Cancer, Recurrent Breast Cancer, Metastatic Breast Cancer, ER+ Breast Cancer, HER2-positive Breast Cancer. This trial tests a combination of two drugs, palbociclib and avelumab, to find the safest doses and see how effective they are. It is for patients with advanced or recurrent triple-negative breast cancer that has specific characteristics (AR+). Participation involves receiving the study drugs and regular medical check-ups, including blood tests and scans. Alternative treatments may include standard chemotherapy or other targeted therapies, depending on prior treatments and cancer type. The trial aims to enroll 45 participants.

Official Summary

This clinical study is aiming to determine the safest doses and schedule for the combination of two drugs named palbociclib and avelumab. The study will also be investigating how effective the combination is for a subgroup of breast cancer patients whose cancer expresses the androgen receptor (AR) but not the oestrogen (hormone) or HER2 receptors. Palbociclib is a drug used in routine care for hormone-receptor (HR) positive and HER2 negative advanced breast cancer, the most common subtype of breast cancer. It is possible that the combination of palbociclib and avelumab will be a more effective cancer treatment than each drug separately, but this is unknown and this study is needed to establish the best dosage and schedule of each drug as well as how effective the combination is.

Who Can Participate

Here is what you need to know about eligibility for this trial. You may be eligible if you have advanced or recurrent breast cancer that is triple-negative and tests positive for the androgen receptor (AR). You must have had at least one, but no more than two, prior chemotherapy treatments for advanced disease. You must be 18 years or older and have a good general health status (WHO performance status 0 or 1). You cannot join if you have certain other health conditions or if you are pregnant or breastfeeding. This trial is studying Triple Negative Breast Cancer, Locally Advanced Breast Cancer, Recurrent Breast Cancer, Metastatic Breast Cancer, ER+ Breast Cancer, HER2-positive Breast Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures will determine the safest dosage of the drug combination and how well it shrinks tumors or stops their growth in patients with AR+ triple-negative breast cancer. The specific primary outcome measures are: Part A: Determine maximum tolerated dose (MTD) of palbociclib plus avelumab in advanced breast cancer (18 month recruitment period); Part B: Determine the confirmed objective response rate of AR+ TNBC patients treated with palbociclib plus avelumab (Up to 24 month recruitment period). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial addresses a significant unmet need in treating a specific subtype of triple-negative breast cancer (AR+), exploring a novel drug combination that may offer a more effective treatment option This research targets Triple Negative Breast Cancer, Locally Advanced Breast Cancer, Recurrent Breast Cancer, Metastatic Breast Cancer, ER+ Breast Cancer, HER2-positive Breast Cancer, where improved treatment options are needed.

Investor Insight

This Phase 1 study is exploring a novel combination for a difficult-to-treat breast cancer subtype, potentially opening a new treatment avenue and indicating future market opportunities if successful. Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of palbociclib and avelumab, and how this trial fits with other treatment options. Participation requires regular visits for drug administration, blood tests, imaging scans, and monitoring for side effects. You will need to use effective contraception during the trial and for a period afterward if you are of childbearing potential. This trial is currently recruiting participants. The trial is being conducted at 9 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 45 participants

Interventions

• DRUG: Palbociclib — Highly selective oral inhibitor of CDK4 and CDK6.
• DRUG: Avelumab — Fully human IgG1 monoclonal antibody (mAb) binds to the PD-L1 cell surface ligand and blocks its interaction with the PD-1 cell surface receptor.

Primary Outcomes

• Part A: Determine maximum tolerated dose (MTD) of palbociclib plus avelumab in advanced breast cancer (18 month recruitment period)
• Part B: Determine the confirmed objective response rate of AR+ TNBC patients treated with palbociclib plus avelumab (Up to 24 month recruitment period)

Secondary Outcomes

• Determine the clinical benefit rate (CR/PR/SD for a minimum of 24 weeks) in AR+ TNBC patients treated with palbociclib plus avelumab (Total 42 month recruitment period)
• Determine the median PFS in AR+ TNBC patients treated with palbociclib plus avelumab (Total 42 month recruitment period)
• Assess the safety and tolerability of palbociclib plus avelumab by recording adverse events until 30 days after the last dose of either study treatment (Total 42 month recruitment period)
• Assess overall survival in both parts A & B (Total 42 month recruitment period)

Full Eligibility Criteria

Inclusion Criteria Part A:

1. Patients with recurrent inoperable locally advanced or metastatic breast cancer.
2. Previously treated with at least one prior line of chemotherapy for advanced disease, but no more than two prior lines of chemotherapy for advanced disease. Patients with ER+ breast cancer must have received at least one prior line of hormone therapy for advanced disease. Patients with HER2+ breast cancer must have received at least one prior line of HER2 directed therapy.
3. Measurable disease (RECIST 1.1)
4. Haematological and biochemical indices within the ranges stated in the study protocol. These measurements must be performed within one week (Day -7 to Day 1) before the patient goes in the trial.
5. Women/female patients with child-bearing potential (defined as the fertile status following menarche and until becoming post-menopausal unless permanently sterile by methods that include hysterectomy, bilateral salpingectomy and bilateral oophorectomy) must have a negative urine or serum pregnancy test within 7 days prior to start of trial.

   Women/females of child bearing potential or their male partners must use a highly effective method of contraception for 2 weeks before starting the study treatment, throughout the treatment period and for 1 month after discontinuation of treatment with palbociclib and avelumab (women/female patients) or 14 weeks (men/male patients). Highly effective methods are defined as methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods, such methods include:
   * Oral, intra-vaginal or transdermal combined hormonal contraception
   * Oral, injectable or implantable progesterone-only contraception
   * Intrauterine device
   * Intrauterine hormone-releasing system,
   * Bilateral tubal occlusion
   * Vasectomised partner
   * True abstinence:\* When this is in line with the preferred and usual lifestyle of the subject

   Key: \* it is only considered highly effective if the patient is refraining from sexual intercourse during the entire period of risk associated with the study treatments
6. 18 years of age or over.
7. World Health Organisation (WHO) performance status 0 or 1
8. Estimated life expectancy of at least 3 months in the opinion of the investigator
9. Signed and dated informed consent.
10. Patients willing and able to comply with scheduled visits, treatment plans, laboratory tests, follow up and other procedures

Inclusion Criteria Part B:

1. Patients with recurrent inoperable locally advanced or metastatic AR+ triple negative breast cancer with ER, PgR and HER2 status determined locally and AR determined centrally on archival metastatic tissue. Archival tissue from the primary tumour (which must have been ER/PgR negative and collected within 5 years prior to metastatic relapse) may be used for AR testing if no archival metastatic tissue is available.
2. Previously treated with at least one prior line of chemotherapy for advanced disease, but no more than two prior lines of chemotherapy for advanced disease.
3. Measurable disease (RECIST 1.1) amenable to fresh biopsy
4. Haematological and biochemical indices within the ranges stated in the study protocol. These measurements must be performed within one week (Day -7 to Day 1) before the patient goes in the trial.
5. Female patients with child-bearing potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.

   Women/females of child bearing potential or their male partners must use a highly effective method of contraception for 2 weeks before starting the study treatment, throughout the treatment period and for 1 month after discontinuation of treatment with palbociclib and avelumab (women/female patients) or 14 weeks (men/male patients). Highly effective methods are defined as methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods, such methods include:
   * Oral, intra-vaginal or transdermal combined hormonal contraception
   * Oral, injectable or implantable progesterone-only contraception
   * Intrauterine device
   * Intrauterine hormone-releasing system,
   * Bilateral tubal occlusion
   * Vasectomised partner
   * True abstinence:\* When this is in line with the preferred and usual lifestyle of the subject

   Key: \* it is only considered highly effective if the patient is refraining from sexual intercourse during the entire period of risk associated with the study treatments
6. Age 18 years of age or over
7. World Health Organisation (WHO) performance status 0 or 1
8. Estimated life expectancy of at least 3 months in the opinion of the investigator
9. Signed and dated informed consent
10. Patients willing and able to comply with scheduled visits, treatment plans, laboratory tests, follow up, and other procedures
11. Available archival breast primar

Trial Locations

• The Christie NHS Foundation Trust, Manchester, Greater Manchester, United Kingdom
• Addenbrooke's Hospital Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
• Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom
• Hope Clinical Trials Cancer Centre, Leicester, United Kingdom
• Barts Cancer Institute, London, United Kingdom
• Royal Marsden NHS Foundation Trust, London, United Kingdom
• University College London Hospitals NHS Foundation Trust, London, United Kingdom
• Nottingham University Hospital, Nottingham, United Kingdom
• Weston Park Hospital, Sheffield, United Kingdom

Frequently Asked Questions

Related Conditions

• Triple Negative Breast Cancer
• Metastatic Breast Cancer
• Locally Advanced Breast Cancer
• Recurrent Breast Cancer
• Hormone Receptor Positive Breast Cancer
• HER2-positive Breast Cancer
• Breast Cancer
• Oncology
• Cancer Therapy
• Immunotherapy

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