PAveMenT: Palbociclib and Avelumab in Metastatic AR+ Triple Negative Breast Cancer

NCT04360941 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CCR4884
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 9

Brief 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.

Conditions

Triple Negative Breast Cancer; Locally Advanced Breast Cancer; Recurrent Breast Cancer; Metastatic Breast Cancer; ER+ Breast Cancer; HER2-positive Breast Cancer

Keywords

Palbociclib; Avelumab; Measurable Disease; Inoperable Disease

Outcome Measures

Primary Outcomes (2)

• Part A: Determine maximum tolerated dose (MTD) of palbociclib plus avelumab in advanced breast cancer

  Define MTD of palbociclib delivered in combination with avelumab

  18 month recruitment period

• Part B: Determine the confirmed objective response rate of AR+ TNBC patients treated with palbociclib plus avelumab

  Response rate assessed by RECIST 1.1 by local radiology review

  Up to 24 month recruitment period

Secondary Outcomes (4)

• 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

Other Outcomes (8)

• RR in patients with PAM50 luminal archival primary tumours compared to PAM50 non luminal as a potential alternative companion diagnostic

  Total 42 month recruitment period

• Determine the RR in patients with PD-L1 positive compared to PDL-1 negative tumours

  Total 42 month recruitment period

• Determine the RR in patients with high versus low mutational load

  Total 42 month recruitment period

Study Arms (1)

Two-part phase 1b trial of induction palbociclib with avelumab

EXPERIMENTAL

Recruitment to Part A will be conducted at the Royal Marsden Hospital only. Up to 18 patients will be recruited for dose escalation of palbociclib in combination with fixed dose avelumab. Part B will recruit at up to 8 high volume centres. Up to 27 patients will be recruited to treatment with the maximum tolerated dose and schedule established in part A. In Part B of the study, additional selection by triple negative histology and positive androgen receptor status will define the study population.

Drug: Palbociclib; Drug: Avelumab

Interventions

Palbociclib DRUG

Highly selective oral inhibitor of CDK4 and CDK6.

Also known as: Ibrance

Two-part phase 1b trial of induction palbociclib with avelumab

Avelumab DRUG

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.

Also known as: Bavencio

Two-part phase 1b trial of induction palbociclib with avelumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with recurrent inoperable locally advanced or metastatic breast cancer.
• 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.
• Measurable disease (RECIST 1.1)
• 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.
• 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
• years of age or over.

You may not qualify if:

• Oral chemotherapy within two weeks, weekly iv chemotherapy within three weeks or any other systemic chemotherapy or investigational medicinal products during the previous four weeks.
• Hormonal therapy within 7 days except luteinizing hormone-releasing hormone (LHRH) analogues for ovarian suppression. Bisphosphonates or RANK ligand antagonists are permitted for the management of bone metastases.
• Previous exposure to immune checkpoint inhibitors or immune co-stimulatory drugs in the advanced setting. (Note: Patients who have received neoadjuvant and/or adjuvant pembrolizumab are eligible if treatment was completed at 6 months prior to metastatic relapse.)
• Previous treatment with palbociclib or any agents which inhibit CDK4/6. (Note: Patients who have received adjuvant abemaciclib or ribociclib for early breast cancer are eligible if treatment was completed at least 12 months prior to metastatic relapse.)
• Major surgery (excluding minor procedures, e.g. placement of vascular access) within 4 weeks or radiation therapy within 14 days prior to study entry
• Patients with known symptomatic brain metastases requiring steroids, untreated brain metastases, leptomeningeal disease or spinal cord compression.
• Active infection requiring systemic therapy
• Any of the following within 12 months prior to study entry: myocardial infarction, history of myocarditis, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack.
• Uncontrolled hypertension or cardiac dysrhythmia including atrial fibrillation
• Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
• Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis (even if fully resolved), pulmonary fibrosis, end stage renal disease on haemodialysis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behaviour; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
• Patients on warfarin or direct acting oral anticoagulants. Patients requiring anticoagulation for rate-controlled AF or previous venous thromboembolism should be switched to low-molecular weight heparin.
• Known HIV or AIDS-related illness, active infection requiring systemic therapy, or positive HBV or HCV test indicating acute or chronic infection
• Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI CTCAE v 5), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead
• Pfizer: collaborator
• Breast Cancer Now: collaborator

Study Sites (9)

The Christie NHS Foundation Trust

Manchester, Greater Manchester, M20 4BX, United Kingdom

RECRUITING

Addenbrooke's Hospital Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

RECRUITING

Hope Clinical Trials Cancer Centre

Leicester, LE1 5WW, United Kingdom

RECRUITING

Barts Cancer Institute

London, EC1M 6BQ, United Kingdom

RECRUITING

Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

RECRUITING

University College London Hospitals NHS Foundation Trust

London, W1T 7HA, United Kingdom

RECRUITING

Nottingham University Hospital

Nottingham, NG5 1PB, United Kingdom

RECRUITING

Weston Park Hospital

Sheffield, S10 2SJ, United Kingdom

RECRUITING

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MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

palbociclib; avelumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Alicia Okines

  The Royal Marsden Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Orla Batchelor

CONTACT

02078082887; pavement.trial@rmh.nhs.uk

Dr Alicia Okines

CONTACT

0207 811 8100; alicia.okines@rmh.nhs.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a two-part phase 1b trial of induction palbociclib with the addition of avelumab. In Part A of the study, the MTD of the study will be determined using a 3+3 design. There will be a 1-week interval between the first and second patients started at each dose level. In Part B, the MTD dose level will be expanded.

Study Record Dates

• First Submitted: April 7, 2020
• First Posted: April 24, 2020
• Study Start: August 11, 2020
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (9)