ER+ HER2- Advanced Breast CancerPhase 1/2CYCAD-1NCT06188520
A First-in-human Dose Escalation and Expansion Study to Evaluate the Safety, and Tolerability of AZD8421 Alone or in Combination in Participants With Selected Advanced or Metastatic Solid Tumors
A Phase 1/2 study testing AZD8421, Camizestrant and Ribociclib in people with ER+ HER2- Advanced Breast Cancer and High-grade Serous Ovarian Cancer (HGSOC), run by AstraZeneca at 13 sites in 5 countries.
Trial summary
This study is designed to evaluate AZD8421 alone and in combination with selected targeted anti-cancer drugs in patients with ER+HER2- advanced breast cancer, and patients with metastatic high-grade serious ovarian cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- ER+ HER2- Advanced Breast Cancer, High-grade Serous Ovarian Cancer (HGSOC)
- What is being tested?
- AZD8421, Camizestrant and Ribociclib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 13 sitesin 5 countries
- Study dates
- 5 Dec 2023to 30 Jun 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female participants only, aged 18 or above
- Participants with advanced solid tumors must have received prior adequate therapy in accordance with local practice for their tumor type and stage of disease, or, in the opinion of the Investigator, a clinical study is the best option for their next treatment based on response to and/or tolerability of prior therapy.
- Metastatic or locoregionally recurrent disease and radiological or objective evidence of progression on or after the last systemic therapy prior to starting IMP.
- ECOG/WHO performance status 0 to 1, and a minimum life expectancy of 12 weeks.
- At least one lesion that is measurable and/or non-measurable, as per RECIST v1.1 and that can be accurately assessed at baseline and is suitable for repeated assessment.
Who cannot join
- Intervention with any of the following:
- Any cytotoxic chemotherapy, investigational agents, or other anti-cancer drugs for the treatment of advanced cancer from a previous treatment regimen or clinical study within 14 days or 5 half-lives (whichever is shorter) of the first dose of IMP (21 days for myelosuppressive therapies) other than GnRHa (eg, goserelin) and bone-stabilizing agents (eg, zoledronic acid, denosumab).
- Any prescription or non-prescription drugs or other products, including herbal products, known to be moderate or strong inhibitors/inducers of CYP3A4/5 which cannot be discontinued prior to first dose of IMP and withheld throughout the study until 2 weeks after the last dose of study drug.
- Drugs that have a known risk of Torsades de Pointes.
- Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of IMP.
- Major surgical procedure or significant traumatic injury, within 4 weeks of the first dose of IMP, or an anticipated need for major surgery and/or any surgery requiring general anesthesia during the study.
Show all 20Show fewer
- Any unresolved toxicities of Grade ≥ 2 from prior anti-cancer therapy (with the exception of alopecia). Participants with stable ≤ Grade 2 neuropathy are eligible.
- Presence of life-threatening metastatic visceral disease, as judged by the Investigator, uncontrolled CNS metastatic disease. Participants with spinal cord compression and/or brain metastases may be enrolled if definitively treated (eg, surgery or radiotherapy) and stable off steroids for at least 4 weeks prior to start of IMP.
- Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, or eg, infection requiring IV antibiotic therapy, or active infection including hepatitis B, hepatitis C, and HIV (active viral infection is defined as requiring antiviral therapy; screening for chronic conditions is not required).
- Any of the following cardiac criteria:
- Mean resting QTcF > 470 msec obtained from a triplicate ECG
- Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (eg, complete left bundle branch block, second- and third-degree heart block), or clinically significant sinus pause. Participants with controlled atrial fibrillation can be enrolled.
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as symptomatic heart failure, hypokalemia, congenital long QT syndrome, immediate family history of long QT syndrome or unexplained sudden death at < 40 years of age. Hypertrophic cardiomyopathy and clinically significant stenotic valve disease.
- LVEF < 50%, and/or experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, unstable angina pectoris, congestive heart failure NYHA Grade ≥ 2, cerebrovascular accident, or transient ischemic attack.
- Uncontrolled hypertension.
- Inadequate bone marrow reserve or organ function as demonstrated by relevant laboratory values:
- Refractory nausea and vomiting, uncontrolled chronic gastrointestinal diseases, or previous significant bowel resection that would preclude adequate absorption of IMP(s).
- History of hypersensitivity to active or inactive excipients of AZD8421 or drugs with a similar chemical structure or class to AZD8421.
- Previous treatment with AZD8421 or with any CDK2-selective inhibitor, or protein kinase membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase 1 (PKMYT1) inhibitor, or WEE1 inhibitor.
- Currently pregnant (confirmed with positive pregnancy test), breast feeding, or planning to become pregnant. Participants of childbearing potential must agree to use one highly effective contraceptive measure.
Trial locations and contacts
13 sites in 5 countries.
13 sites in 5 countries
United States4 sites
Research Site
Houston, Texas, 77030
Research Site
Nashville, Tennessee, 37201
Research Site
Providence, Rhode Island, 02903
Research Site
St Louis, Missouri, 63141
Spain3 sites
Research Site
Barcelona, 8035
Research Site
Pamplona, 31005
Research Site
Valencia, 46010
United Kingdom3 sites
Research Site
Cambridge, CB2 0XY
Research Site
London, EC1A 7BE
Research Site
Manchester, M20 4BX
About this study
Official title: A Phase I/IIa, First-in-human, Open-label, Dose Escalation and Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of AZD8421 Alone or in Combination in Participants With Selected Advanced or Metastatic Solid Tumors
This study is designed to evaluate AZD8421 alone and in combination with selected targeted anti-cancer drugs in patients with ER+HER2- advanced breast cancer, and patients with metastatic high-grade serious ovarian cancer.
Read the detailed description
This is a first in-human study of AZD8421 administered to participants with advanced or metastatic solid tumors. The study will evaluate the safety, tolerability, preliminary efficacy, pharmacokinetics, and pharmacodynamics of AZD8421 alone and in combination with selected targeted anti-cancer drugs.
AZD8421 monotherapy (M1) will evaluate the safety, tolerability and pharmacokinetics of AZD8421 as monotherapy to identify a recommended Phase II dose (RP2D) in participants with ER+ HER2- advanced breast cancer previously treated with a CDK4/6i (Parts A and B) and participants with metastatic high-grade serous ovarian cancer previously treated with a platinum-based chemotherapy in the metastatic setting (Part B).
AZD8421 combination therapy (M2) will evaluate the safety, tolerability, and pharmacokinetics of different formulations of AZD8421 in combination with a CDK4/6 inhibitor (one or more of abemaciclib, ribociclib and palbociclib) and camizestrant (next generation oral SERD; referred to throughout as 'camizestrant') in participants with ER+ HER2- advanced breast cancer previously treated with a CDK4/6 inhibitor.
- Being tested
- AZD8421, Camizestrant, Ribociclib, Palbociclib, Abemaciclib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD8421Drug
CDK2 inhibitor
CamizestrantDrug
Also called AZD9833
SERD
RibociclibDrug
Also called Kisqali
CDK4/6 inhibitor
PalbociclibDrug
Also called Ibrance
CDK4/6 inhibitor
AbemaciclibDrug
Also called Verzenios
CDK4/6 inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Module 1 | Experimental | AZD8421 monotherapy Receives: Drug: AZD8421 |
| Module 2A | Experimental | AZD8421 with camizestrant and CDK4/6 inhibitor Receives: Drug: AZD8421; Drug: Camizestrant; Drug: Ribociclib; Drug: Palbociclib; Drug: Abemaciclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose limiting toxicities (DLTs) as defined in the protocol.
Percentage of participants with incidence of DLTs.
Measured: From start of treatment until the end of DLT period, assessed up to 28 days.
Incidence of AEs/SAEs
Percentage of participants with incidence of AEs/SAEs.
Measured: From start of treatment until the end of safety follow-up, approximately 18 months.
Clinically significant changes from baseline in clinical laboratory parameters, vital signs and ECGs.
Percentage of participants with clinically significant changes from baseline in clinical laboratory parameters, vital signs and ECGs.
Measured: From start of treatment until the end of safety follow-up, approximately 18 months.
Discontinuation of AZD8421 due to toxicity
Percentage of participants that have discontinued AZD8421 due to toxicity.
Measured: From start of treatment until the end of safety follow-up, approximately 18 months.
Secondary outcomes (30)
Overall Response Rate (ORR)
The percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR), according to RECIST v1.1, that occur prior to disease progression and/or initiation of subsequent anti-cancer therapy.
Measured: 8 weeks from start of treatment until end of treatment or objective disease progression, approximately 18 months.
Duration of Response (DoR)
The time from the date of first documented objective response (which is subsequently confirmed) until date of first documented disease progression or death (by any cause in the absence of disease progression).
Measured: 8 weeks from start of treatment until end of treatment or objective disease progression, approximately 18 months.
Disease control rate (DCR)
The percentage of participants who have a best objective response of confirmed CR or PR or who have SD for at least 23 weeks after start of treatment.
Measured: 24 weeks after the start of treatment.
Percentage change in tumor size
The largest decrease (or smallest increase) in tumor size from baseline for a participant, using RECIST v1.1 assessments
Measured: From start of treatment through to EOT, progressive disease, death (in the absence of progression), start of subsequent anti-cancer therapy, whichever occurs first, approximately 18 months.
Progression Free Survival (PFS)
Progression-free survival is defined as the time from the start of treatment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the participant withdraws from therapy or receives another anti-cancer therapy prior to progression.
Measured: From start of treatment through to progressive disease, death (in the absence of progression), EOT (last evaluable disease assessment), whichever occurs first, approximately 18 months.
PK of AZD8421 (Cmax)
To characterize the PK profiles and parameters of AZD8421 and its metabolites after monotherapy and also in combination with other anti-cancer drugs after single and multiple doses when administered to participants with ER+ HER2- metastatic breast cancer and other advanced solid tumors.
Descriptive statistics of following PK parameters:
After single dose; Cmax; to measure maximum plasma concentration after oral administration.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (Tmax)
To characterize the PK profiles and parameters of AZD8421 and its metabolites after monotherapy and also in combination with other anti-cancer drugs after single and multiple doses when administered to participants with ER+ HER2- metastatic breast cancer and other advanced solid tumors.
Descriptive statistics of following PK parameters:
After single dose; Tmax; to measure time to reach maximum plasma concentration.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (AUCinf)
To characterize the PK profiles and parameters of AZD8421 and its metabolites after monotherapy and also in combination with other anti-cancer drugs after single and multiple doses when administered to participants with ER+ HER2- metastatic breast cancer and other advanced solid tumors.
Descriptive statistics of following PK parameters:
After single dose; AUCinf; to measure the area under the plasma concentration-time curve from time 0 to infinity.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (AUClast)
To characterize the PK profiles and parameters of AZD8421 and its metabolites after monotherapy and also in combination with other anti-cancer drugs after single and multiple doses when administered to participants with ER+ HER2- metastatic breast cancer and other advanced solid tumors.
Descriptive statistics of following PK parameters:
After single dose; AUClast; to measure area under the plasma concentration-time curve from time zero to last PK sample.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (T1/2λZ)
To characterize the PK profiles and parameters of AZD8421 and its metabolites after monotherapy and also in combination with other anti-cancer drugs after single and multiple doses when administered to participants with ER+ HER2- metastatic breast cancer and other advanced solid tumors.
Descriptive statistics of following PK parameters:
After single dose; T1/2λZ; to measure the terminal elimination half-life.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (CL/F)
To characterize the PK profiles and parameters of AZD8421 and its metabolites after monotherapy and also in combination with other anti-cancer drugs after single and multiple doses when administered to participants with ER+ HER2- metastatic breast cancer and other advanced solid tumors.
Descriptive statistics of following PK parameters:
After single dose; CL/F; to measure apparent clearance after oral administration.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (Cssmax)
To characterize the PK profiles and parameters of AZD8421 and its metabolites after monotherapy and also in combination with other anti-cancer drugs after single and multiple doses when administered to participants with ER+ HER2- metastatic breast cancer and other advanced solid tumors.
Descriptive statistics of following PK parameters:
After multiple doses; Cssmax; to measure maximum concentration after oral administration at steady state.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (Tssmax)
To characterize the PK profiles and parameters of AZD8421 and its metabolites after monotherapy and also in combination with other anti-cancer drugs after single and multiple doses when administered to participants with ER+ HER2- metastatic breast cancer and other advanced solid tumors.
Descriptive statistics of following PK parameters:
After multiple doses; Tssmax; to measure time it takes to achieve maximum plasma concentration at steady state.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (ARCmax)
To characterize the PK profiles and parameters of AZD8421 and its metabolites after monotherapy and also in combination with other anti-cancer drugs after multiple doses when administered to participants with ER+ HER2- metastatic breast cancer and other advanced solid tumors.
Descriptive statistics of following PK parameters:
After multiple doses; ARCmax; to measure accumulation ratio of Cmax.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (AUCsslast)
To characterize the PK profiles and parameters of AZD8421 and its metabolites after monotherapy and also in combination with other anti-cancer drugs after single and multiple doses when administered to participants with ER+ HER2- metastatic breast cancer and other advanced solid tumors.
Descriptive statistics of following PK parameters:
After multiple doses; AUCsslast; to measure the area under plasma-concentration time curve from time zero to last PK sample at steady state.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (T1/2λssz)
To characterize the PK profiles and parameters of AZD8421 and its metabolites after monotherapy and also in combination with other anti-cancer drugs after single and multiple doses when administered to participants with ER+ HER2- metastatic breast cancer and other advanced solid tumors.
Descriptive statistics of following PK parameters:
After multiple doses; T1/2λssz; to measure terminal elimination half-life at steady state.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (CLss/F)
To characterize the PK profiles and parameters of AZD8421 and its metabolites after monotherapy and also in combination with other anti-cancer drugs after single and multiple doses when administered to participants with ER+ HER2- metastatic breast cancer and other advanced solid tumors.
Descriptive statistics of following PK parameters:
After multiple doses; CLss/F; to measure apparent oral clearance at steady state.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421, camizestrant, and CDK4/6i (Cmax) (M2 only)
Evaluate pharmacokinetics profiles of AZD8421, camizestrant, and CDK4/6i when administered in combination.
For AZD8421 and where possible CDK4/6i and their metabolites, and camizestrant; descriptive statistics of the following PK parameters:
After single dose: Cmax; to measure maximum plasma concentration after oral administration.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421, camizestrant and CDK4/6i.
PK of AZD8421, camizestrant, and CDK4/6i (Tmax) (M2 only)
Evaluate pharmacokinetics profiles of AZD8421, camizestrant, and CDK4/6i when administered in combination.
For AZD8421 and where possible CDK4/6i and their metabolites, and camizestrant; descriptive statistics of the following PK parameters:
After single dose: Tmax; to measure the time it takes to achieve maximum plasma concentration after oral administration.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421, camizestrant and CDK4/6i.
PK of AZD8421, camizestrant, and CDK4/6i (AUCinf) (M2 only)
Evaluate pharmacokinetics profiles of AZD8421, camizestrant, and CDK4/6i when administered in combination.
For AZD8421 and where possible CDK4/6i and their metabolites, and camizestrant; descriptive statistics of the following PK parameters:
After single dose: AUCinf; to measure area under plasma concentration-time curve from time zero to infinity.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421, camizestrant and CDK4/6i.
PK of AZD8421, camizestrant, and CDK4/6i (T1/2λ) (M2 only)
Evaluate pharmacokinetics profiles of AZD8421, camizestrant, and CDK4/6i when administered in combination.
For AZD8421 and where possible CDK4/6i and their metabolites, and camizestrant; descriptive statistics of the following PK parameters:
After single dose: T1/2λZ; to measure terminal elimination half-life.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421, camizestrant and CDK4/6i.
PK of AZD8421, camizestrant, and CDK4/6i (CL/F) (M2 only)
Evaluate pharmacokinetics profiles of AZD8421, camizestrant, and CDK4/6i when administered in combination.
For AZD8421 and where possible CDK4/6i and their metabolites, and camizestrant; descriptive statistics of the following PK parameters:
After single dose: CL/F; to measure apparent clearance after oral administration.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421, camizestrant and CDK4/6i.
PK of AZD8421, camizestrant, and CDK4/6i (Cssmax) (M2 only)
Evaluate pharmacokinetics profiles of AZD8421, camizestrant, and CDK4/6i when administered in combination.
For AZD8421 and where possible CDK4/6i and their metabolites, and camizestrant; descriptive statistics of the following PK parameters:
After multiple doses: Cssmax; to measure the maximum plasma concentration after oral administration at steady state.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421, camizestrant and CDK4/6i.
PK of AZD8421, camizestrant, and CDK4/6i (Tssmax) (M2 only)
Evaluate pharmacokinetics profiles of AZD8421, camizestrant, and CDK4/6i when administered in combination.
For AZD8421 and where possible CDK4/6i and their metabolites, and camizestrant; descriptive statistics of the following PK parameters:
After multiple doses: Tssmax; to measure time it takes to achieve maximum plasma concentration after oral administration at steady state.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421, camizestrant and CDK4/6i.
PK of AZD8421, camizestrant, and CDK4/6i (AUC0-tau) (M2 only)
Evaluate pharmacokinetics profiles of AZD8421, camizestrant, and CDK4/6i when administered in combination.
For AZD8421 and where possible CDK4/6i and their metabolites, and camizestrant; descriptive statistics of the following PK parameters:
After multiple doses: AUC0-tau; to measure area under plasma-concentration-time curve within dosing interval.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421, camizestrant and CDK4/6i.
PK of AZD8421, camizestrant, and CDK4/6i (T1/2λssz) (M2 only)
Evaluate pharmacokinetics profiles of AZD8421, camizestrant, and CDK4/6i when administered in combination.
For AZD8421 and where possible CDK4/6i and their metabolites, and camizestrant; descriptive statistics of the following PK parameters:
After multiple doses: T1/2λssz; to measure terminal elimination half-life at steady state.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421, camizestrant and CDK4/6i.
PK of AZD8421, camizestrant, and CDK4/6i (CLss/F) (M2 only)
Evaluate pharmacokinetics profiles of AZD8421, camizestrant, and CDK4/6i when administered in combination.
For AZD8421 and where possible CDK4/6i and their metabolites, and camizestrant; descriptive statistics of the following PK parameters:
After multiple doses: CLss/F; to measure apparent clearance after oral administration at steady state.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421, camizestrant and CDK4/6i.
PD of AZD8421 (M1B only)
To assess pharmacodynamic activity of AZD8421 monotherapy by assessment of candidate biomarker in baseline and on-treatment tumor and blood samples in participants with ER+ HER2- metastatic breast cancer and other advanced solid tumors.
Measured: Baseline and Cycle 1 Day 15.
PK of AZD8421 (ARAUC)
To characterize the PK profiles and parameters of AZD8421 and its metabolites after monotherapy and also in combination with other anti-cancer drugs after multiple doses when administered to participants with ER+ HER2- metastatic breast cancer and other advanced solid tumors.
Descriptive statistics of following PK parameters:
After multiple doses measure accumulation ratio of AUC.
Measured: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
Best Objective Response (BOR)
The best response a participant has had following start of dosing, but prior to starting any subsequent cancer therapy and up to and including date of first documented disease progression, last evaluable assessment or death (by any cause in the absence of disease progression).
Measured: 8 weeks from start of treatment until end of treatment or objective disease progression, approximately 18 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2024
- Study start5 Dec 2023
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ER+ HER2- Advanced Breast CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Richard Baird, MD, PhD, Study chair, Cambridge University Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06188520
- Sponsor's protocol ID
- D8470C00001
- Other IDs
- 2023-507305-33-00, 2023
- Acronym
- CYCAD-1
- Status last verified
- Oct 2026
- First submitted
- 1 Dec 2023
- Last updated
- 28 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IIa, First-in-human, Open-label, Dose Escalation and Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of AZD8421 Alone or in Combination in Participants With Selected Advanced or Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT06188520
- Acronym / sponsor ID
- CYCAD-1 / D8470C00001
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 55 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 5 Dec 2023 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 3 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to evaluate AZD8421 alone and in combination with selected targeted anti-cancer drugs in patients with ER+HER2- advanced breast cancer, and patients with metastatic high-grade serious ovarian cancer.
Detailed description
This is a first in-human study of AZD8421 administered to participants with advanced or metastatic solid tumors. The study will evaluate the safety, tolerability, preliminary efficacy, pharmacokinetics, and pharmacodynamics of AZD8421 alone and in combination with selected targeted anti-cancer drugs.
AZD8421 monotherapy (M1) will evaluate the safety, tolerability and pharmacokinetics of AZD8421 as monotherapy to identify a recommended Phase II dose (RP2D) in participants with ER+ HER2- advanced breast cancer previously treated with a CDK4/6i (Parts A and B) and participants with metastatic high-grade serous ovarian cancer previously treated with a platinum-based chemotherapy in the metastatic setting (Part B).
AZD8421 combination therapy (M2) will evaluate the safety, tolerability, and pharmacokinetics of different formulations of AZD8421 in combination with a CDK4/6 inhibitor (one or more of abemaciclib, ribociclib and palbociclib) and camizestrant (next generation oral SERD; referred to throughout as 'camizestrant') in participants with ER+ HER2- advanced breast cancer previously treated with a CDK4/6 inhibitor.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Module 1 | Experimental | Drug: AZD8421AZD8421 monotherapy |
| Module 2A | Experimental | Drug: AZD8421, Drug: Camizestrant, Drug: Ribociclib, Drug: Palbociclib, Drug: AbemaciclibAZD8421 with camizestrant and CDK4/6 inhibitor |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Female participants only, aged 18 or above
- Participants with advanced solid tumors must have received prior adequate therapy in accordance with local practice for their tumor type and stage of disease, or, in the opinion of the Investigator, a clinical study is the best option for their next treatment based on response to and/or tolerability of prior therapy.
- Metastatic or locoregionally recurrent disease and radiological or objective evidence of progression on or after the last systemic therapy prior to starting IMP.
- ECOG/WHO performance status 0 to 1, and a minimum life expectancy of 12 weeks.
- At least one lesion that is measurable and/or non-measurable, as per RECIST v1.1 and that can be accurately assessed at baseline and is suitable for repeated assessment.
Key exclusion criteria (20 listed)
- Intervention with any of the following:
- Any cytotoxic chemotherapy, investigational agents, or other anti-cancer drugs for the treatment of advanced cancer from a previous treatment regimen or clinical study within 14 days or 5 half-lives (whichever is shorter) of the first dose of IMP (21 days for myelosuppressive therapies) other than GnRHa (eg, goserelin) and bone-stabilizing agents (eg, zoledronic acid, denosumab).
- Any prescription or non-prescription drugs or other products, including herbal products, known to be moderate or strong inhibitors/inducers of CYP3A4/5 which cannot be discontinued prior to first dose of IMP and withheld throughout the study until 2 weeks after the last dose of study drug.
- Drugs that have a known risk of Torsades de Pointes.
- Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of IMP.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD8421CDK2 inhibitor | Drug | Module 1, Module 2A |
| CamizestrantAlso: AZD9833SERD | Drug | Module 2A |
| RibociclibAlso: KisqaliCDK4/6 inhibitor | Drug | Module 2A |
| PalbociclibAlso: IbranceCDK4/6 inhibitor | Drug | Module 2A |
| AbemaciclibAlso: VerzeniosCDK4/6 inhibitor | Drug | Module 2A |
Primary outcome
Incidence of dose limiting toxicities (DLTs) as defined in the protocol.
Time frame: From start of treatment until the end of DLT period, assessed up to 28 days.
Percentage of participants with incidence of DLTs.
Incidence of AEs/SAEs
Time frame: From start of treatment until the end of safety follow-up, approximately 18 months.
Percentage of participants with incidence of AEs/SAEs.
Clinically significant changes from baseline in clinical laboratory parameters, vital signs and ECGs.
Time frame: From start of treatment until the end of safety follow-up, approximately 18 months.
Percentage of participants with clinically significant changes from baseline in clinical laboratory parameters, vital signs and ECGs.
Discontinuation of AZD8421 due to toxicity
Time frame: From start of treatment until the end of safety follow-up, approximately 18 months.
Percentage of participants that have discontinued AZD8421 due to toxicity.
30 secondary outcomes
Overall Response Rate (ORR)
Time frame: 8 weeks from start of treatment until end of treatment or objective disease progression, approximately 18 months.
Duration of Response (DoR)
Time frame: 8 weeks from start of treatment until end of treatment or objective disease progression, approximately 18 months.
Disease control rate (DCR)
Time frame: 24 weeks after the start of treatment.
Percentage change in tumor size
Time frame: From start of treatment through to EOT, progressive disease, death (in the absence of progression), start of subsequent anti-cancer therapy, whichever occurs first, approximately 18 months.
Progression Free Survival (PFS)
Time frame: From start of treatment through to progressive disease, death (in the absence of progression), EOT (last evaluable disease assessment), whichever occurs first, approximately 18 months.
PK of AZD8421 (Cmax)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (Tmax)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (AUCinf)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (AUClast)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (T1/2λZ)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (CL/F)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (Cssmax)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (Tssmax)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (ARCmax)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (AUCsslast)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (T1/2λssz)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421 (CLss/F)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
PK of AZD8421, camizestrant, and CDK4/6i (Cmax) (M2 only)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421, camizestrant and CDK4/6i.
PK of AZD8421, camizestrant, and CDK4/6i (Tmax) (M2 only)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421, camizestrant and CDK4/6i.
PK of AZD8421, camizestrant, and CDK4/6i (AUCinf) (M2 only)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421, camizestrant and CDK4/6i.
PK of AZD8421, camizestrant, and CDK4/6i (T1/2λ) (M2 only)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421, camizestrant and CDK4/6i.
PK of AZD8421, camizestrant, and CDK4/6i (CL/F) (M2 only)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421, camizestrant and CDK4/6i.
PK of AZD8421, camizestrant, and CDK4/6i (Cssmax) (M2 only)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421, camizestrant and CDK4/6i.
PK of AZD8421, camizestrant, and CDK4/6i (Tssmax) (M2 only)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421, camizestrant and CDK4/6i.
PK of AZD8421, camizestrant, and CDK4/6i (AUC0-tau) (M2 only)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421, camizestrant and CDK4/6i.
PK of AZD8421, camizestrant, and CDK4/6i (T1/2λssz) (M2 only)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421, camizestrant and CDK4/6i.
PK of AZD8421, camizestrant, and CDK4/6i (CLss/F) (M2 only)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421, camizestrant and CDK4/6i.
PD of AZD8421 (M1B only)
Time frame: Baseline and Cycle 1 Day 15.
PK of AZD8421 (ARAUC)
Time frame: From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
Best Objective Response (BOR)
Time frame: 8 weeks from start of treatment until end of treatment or objective disease progression, approximately 18 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2026.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Related trials for ER+ HER2- Advanced Breast Cancer
RecruitingPhase 2
Study of PF-07248144 in Advanced or Metastatic Solid Tumors
Locally Advanced or Metastatic ER+ HER2- Breast Cancer, Locally Advanced or Metastatic Castration-resistant Prostate Cancer
RecruitingPhase 1/2
Trial of 225Ac-DOTATATE (RYZ101) in Subjects With ER+, HER2-negative Unresectable or Metastatic Breast Cancer Expressing SSTRs.
Metastatic Breast Cancer, HER2-negative Breast Cancer
RecruitingPhase 1
Phase 1 Study of OP-3136 in Advanced or Metastatic Solid Tumors
Advanced or Metastatic ER+ HER2- Breast Cancer (mBC), Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)
RecruitingPhase 1/2
The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)
Advanced Solid Tumor, Advanced Malignant Neoplasm
RecruitingPhase 3
Palazestrant in Combination With Ribociclib for the First-line Treatment of ER+/HER2- Advanced Breast Cancer
Breast Cancer, Locally Advanced Breast Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Baird, MD, PhD study chair
Cambridge University Hospitals
13 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AZD8421, Camizestrant and Ribociclib in people with ER+ HER2- Advanced Breast Cancer and High-grade Serous Ovarian Cancer (HGSOC), run by AstraZeneca at 13 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Spain, United Kingdom, South Korea, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose limiting toxicities (DLTs) as defined in the protocol. (time frame: From start of treatment until the end of DLT period, assessed up to 28 days.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026; AzTrials last refreshed its copy on 2 Nov 2026.