Efficacy and Safety of Camizestrant Plus Ribociclib in Patients With Breast Cancer

NCT07195227 | Not Yet Recruiting Phase 2

• 1 other identifier: MEDOPP555
• Study Type: interventional
• Target: 150
• Locations: 0 countries
• Sites: N/A

Brief Summary

This trial will study a type of breast cancer defined by the expression of hormone receptor in the cancer cells (HR+). Patients will be treated with ribociclib, a cyclin-dependent kinase inhibitor, and camizestrant, a selective estrogen receptor degrader (SERD) and complete ER antagonist. The main purpose of the Study is to analyze the efficacy (to find out how effective a treatment is) of ribociclib in combination with camizestrant in patients with advanced HR+ breast cancer who have received endocrine therapy (ET) in early breast cancer setting for at least 5 years, of which at least 2 years with aromatase inhibitor (AI). Ribociclib plus camizestrant efficacy will be determined by assessing the period from treatment initiation until disease progression, defined as progression free survival (PFS). The anticipated favorable clinical benefits of the combination of ribociclib and camizestrant therapy are projected to outweigh the risks of this treatment. This Study will be performed in full compliance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and all applicable local Good Clinical Practice (GCP) and regulations.

Conditions

Hormon Receptor Positive Breast Cancer; Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS, defined as the time from the date of the first dose until the first occurrence of disease progression or death from any cause, whichever occurs first, as determined locally by the investigator using Response Evaluation Criteria In Solid Tumors (RECIST) v.1.1.

  Up to 28 months

Secondary Outcomes (9)

• Overall Response Rate (ORR)

  Up to 28 months

• Clinical Benefit Rate (CBR)

  up to 28 months

• Time to Response (TTR)

  Up to 28 months

• Duration of Response (DoR)

  Up to 28 months

• Best percentage of change

  Up to 28 months

Study Arms (2)

Experimental Arm A: Camizestrant and Ribociclib

EXPERIMENTAL

Patients will receive Camizestrant (75 mg, oral, every day on each day of the 28-day cycle) and Ribociclib (600 mg, oral, every day, on day 1 to 21 of each 28-day cycle)

Drug: Camizestrant; Drug: Ribociclib

Control Arm B: Historical Arm

NO INTERVENTION

The clinical Study comparator will be a historical control arm containing data from all or some of the following clinical trials: MONALEESA-2, MONALEESA-3, MONALEESA-7, CompLEEment-1, and RIBECCA.

Interventions

Camizestrant DRUG

Next-generation oral SERD molecule that is intended for the treatment of women and men with ER+ breast cancer. In addition to degradation of ERα, camizestrant also acts as a pure ER antagonist

Experimental Arm A: Camizestrant and Ribociclib

Ribociclib DRUG

Selective inhibitor of CDK 4 and 6, with 50% inhibition (IC50) values of 0.01 μM (4.3 ng/ml) and 0.039 μM (16.9 ng/ml) in biochemical assays, respectively. These kinases are activated by binding to D-cyclins and are crucial to cell cycle progression and cellular proliferation. The cyclin D-CDK4/6 complex regulates the cell cycle by phosphorylating the retinoblastoma protein (pRb).

Experimental Arm A: Camizestrant and Ribociclib

Eligibility Criteria

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

You may qualify if:

• Patient must be capable of understanding the purpose of the Study and have signed the written informed consent form (ICF) prior to beginning specific protocol procedures.
• Female or male patients ≥ 18 years of age at the time of signing ICF.
• Pre- or peri-menopausal women or men. are eligible if treated with a Luteinizing hormone-releasing hormone (LHRH) analogue. Treatment with a LHRH is recommended for at least 28 days prior to study treatment; if shorter, post-menopausal levels of serum estradiol/follicle-stimulating hormone \[FSH\] must be confirmed analytically prior to Study enrollment.
• Post-menopausal women, defined by any of the following criteria:
• Cessation of menses for at least 12 consecutive months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
• Documented bilateral surgical oophorectomy.
• Documented histologically confirmed HR+ and human epidermal growth factor receptor 2 (HER2)-negative breast cancer according to the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines as per local assessment on the most recent analyzed biopsy. Therefore, tumors must be:
• o HR+ defined as ≥ 10% of tumor cells stain positive for estrogen receptor (ER) on immunohistochemistry (IHC), and HER2- defined as 0 or 1+ intensity on IHC, or 2+ intensity on IHC and no evidence of amplification on in situ hybridization (ISH).
• Unresectable locally recurrent or metastatic disease confirmed by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent.
• Patients must have received at least five years of adjuvant endocrine therapy, including at least two years of an AI (capped to 30% patients with treatment-free interval \[TFI\] ≥ 12 months.
• Patients must have:
• Radiological evidence of progression while on, or within 12 months of the end of (neo)adjuvant endocrine therapy (secondary endocrine resistance criteria), or
• Radiological evidence of progression more than 12 months of the end of (neo)adjuvant endocrine therapy (endocrine sensitive criteria).
• Patients receiving a CDK4/6 inhibitor-based therapy in the (neo)adjuvant setting are eligible if disease progression is confirmed more than 12 months following CDK4/6 inhibitor treatment completion in this scenario.
• Evidence of measurable disease as per RECIST v.1.1, or non-measurable, but evaluable, disease, including bone-only disease with at least one lytic or mixed lytic-blastic bone lesion.

You may not qualify if:

• Formal contraindication to endocrine therapy defined as visceral crisis and/or rapidly or symptomatic progressive visceral disease.
• Current participation in another therapeutic clinical trial.
• Has previously been treated with any SERD, including camizestrant, experimental ETs or fulvestrant.
• Prior systemic therapy for advanced disease.
• Known active uncontrolled or symptomatic central nervous system (CNS) metastases and/or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases are eligible if they have been previously treated with local therapy, are clinically stable, and off anticonvulsants and steroids for at least 14 days before the first dose of Study treatment.
• History of another primary malignancy except for the following:
• Malignancy treated with curative intent with no known active disease ≥ 3 years before the first dose of Study treatment, and of very low potential risk for recurrence.
• Adequately treated non-melanoma skin cancer or lentigo malignancy without evidence of disease.
• Other exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin.
• Note: For other cancers considered to have a low risk of recurrence, discussion with the Medical Monitor is required.
• Known allergy or hypersensitivity reaction to any investigational medicinal products (IMPs) or their incorporated substances.
• Note: Ribociclib is contraindicated for patients with hypersensitivity/allergy to peanut or soya.
• History of malabsorption syndrome or other condition that would interfere with enteral absorption (ongoing gastrointestinal obstruction/motility disorder, malabsorption syndrome, or prior gastric bypass) or results in the inability or unwillingness to swallow pills.
• Palliative radiotherapy with a limited field of radiation within two weeks or with wide field of radiation or radiation to more than 30% of the bone marrow within four weeks prior to Study enrollment.
• Major surgical procedure or significant traumatic injury within 14 days before Study enrollment.

Sponsors & Collaborators

• MedSIR: lead

MeSH Terms

Conditions

Breast Neoplasms

Interventions

AZD9833; ribociclib

Condition Hierarchy (Ancestors)

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

Central Study Contacts

MEDSIR

CONTACT

+ 34 932 214 135; contact.trials@medsir.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2025
• First Posted: September 26, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: October 2, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share