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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06188520




Registration number
NCT06188520
Ethics application status
Date submitted
1/12/2023
Date registered
3/01/2024

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
D8470C00001
Universal Trial Number (UTN)
Trial acronym
CYCAD-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
ER+ HER2- Advanced Breast Cancer 0 0
High-grade Serous Ovarian Cancer (HGSOC) 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AZD8421
Treatment: Drugs - Camizestrant
Treatment: Drugs - Ribociclib
Treatment: Drugs - Palbociclib
Treatment: Drugs - Abemaciclib

Experimental: Module 1 - AZD8421 monotherapy

Experimental: Module 2A_abema - AZD8421 with camizestrant and abemaciclib

Experimental: Module 2A_ribo - AZD8421 with camizestrant and ribociclib

Experimental: Module 2A_palbo - AZD8421 with camizestrant and palbociclib


Treatment: Drugs: AZD8421
CDK2 inhibitor

Treatment: Drugs: Camizestrant
SERD

Treatment: Drugs: Ribociclib
CDK4/6 inhibitor

Treatment: Drugs: Palbociclib
CDK4/6 inhibitor

Treatment: Drugs: Abemaciclib
CDK4/6 inhibitor
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of dose limiting toxicities (DLTs) as defined in the protocol.
Timepoint [1] 0 0
From start of treatment until the end of DLT period, assessed up to 28 days.
Primary outcome [2] 0 0
Incidence of AEs/SAEs
Timepoint [2] 0 0
From start of treatment until the end of safety follow-up, approximately 18 months.
Primary outcome [3] 0 0
Clinically significant changes from baseline in clinical laboratory parameters, vital signs and ECGs.
Timepoint [3] 0 0
From start of treatment until the end of safety follow-up, approximately 18 months.
Primary outcome [4] 0 0
Discontinuation of AZD8421 due to toxicity
Timepoint [4] 0 0
From start of treatment until the end of safety follow-up, approximately 18 months.
Secondary outcome [1] 0 0
Overall Response Rate (ORR)
Timepoint [1] 0 0
8 weeks from start of treatment until end of treatment or objective disease progression, approximately 18 months.
Secondary outcome [2] 0 0
Duration of Response (DoR)
Timepoint [2] 0 0
8 weeks from start of treatment until end of treatment or objective disease progression, approximately 18 months.
Secondary outcome [3] 0 0
Disease control rate (DCR)
Timepoint [3] 0 0
24 weeks after the start of treatment.
Secondary outcome [4] 0 0
Percentage change in tumor size
Timepoint [4] 0 0
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.
Secondary outcome [5] 0 0
Progression Free Survival (PFS)
Timepoint [5] 0 0
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.
Secondary outcome [6] 0 0
PK of AZD8421 (Cmax)
Timepoint [6] 0 0
From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
Secondary outcome [7] 0 0
PK of AZD8421 (Tmax)
Timepoint [7] 0 0
From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
Secondary outcome [8] 0 0
PK of AZD8421 (AUCinf)
Timepoint [8] 0 0
From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
Secondary outcome [9] 0 0
PK of AZD8421 (AUClast)
Timepoint [9] 0 0
From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
Secondary outcome [10] 0 0
PK of AZD8421 (T1/2?Z)
Timepoint [10] 0 0
From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
Secondary outcome [11] 0 0
PK of AZD8421 (CL/F)
Timepoint [11] 0 0
From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
Secondary outcome [12] 0 0
PK of AZD8421 (Cssmax)
Timepoint [12] 0 0
From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
Secondary outcome [13] 0 0
PK of AZD8421 (Tssmax)
Timepoint [13] 0 0
From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
Secondary outcome [14] 0 0
PK of AZD8421 (AUC0-tau)
Timepoint [14] 0 0
From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
Secondary outcome [15] 0 0
PK of AZD8421 (AUCsslast)
Timepoint [15] 0 0
From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
Secondary outcome [16] 0 0
PK of AZD8421 (T1/2?ssz)
Timepoint [16] 0 0
From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
Secondary outcome [17] 0 0
PK of AZD8421 (CLss/F)
Timepoint [17] 0 0
From start of treatment, at predefined intervals up to Cycle 6, approximately 6 months (each cycle is 28 days) of the administration of AZD8421.
Secondary outcome [18] 0 0
PK of AZD8421, camizestrant, and CDK4/6i (Cmax) (M2 only)
Timepoint [18] 0 0
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.
Secondary outcome [19] 0 0
PK of AZD8421, camizestrant, and CDK4/6i (Tmax) (M2 only)
Timepoint [19] 0 0
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.
Secondary outcome [20] 0 0
PK of AZD8421, camizestrant, and CDK4/6i (AUCinf) (M2 only)
Timepoint [20] 0 0
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.
Secondary outcome [21] 0 0
PK of AZD8421, camizestrant, and CDK4/6i (T1/2?) (M2 only)
Timepoint [21] 0 0
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.
Secondary outcome [22] 0 0
PK of AZD8421, camizestrant, and CDK4/6i (CL/F) (M2 only)
Timepoint [22] 0 0
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.
Secondary outcome [23] 0 0
PK of AZD8421, camizestrant, and CDK4/6i (Cssmax) (M2 only)
Timepoint [23] 0 0
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.
Secondary outcome [24] 0 0
PK of AZD8421, camizestrant, and CDK4/6i (Tssmax) (M2 only)
Timepoint [24] 0 0
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.
Secondary outcome [25] 0 0
PK of AZD8421, camizestrant, and CDK4/6i (AUC0-tau) (M2 only)
Timepoint [25] 0 0
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.
Secondary outcome [26] 0 0
PK of AZD8421, camizestrant, and CDK4/6i (T1/2?ssz) (M2 only)
Timepoint [26] 0 0
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.
Secondary outcome [27] 0 0
PK of AZD8421, camizestrant, and CDK4/6i (CLss/F) (M2 only)
Timepoint [27] 0 0
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.
Secondary outcome [28] 0 0
Overall survival (M1 and M2)
Timepoint [28] 0 0
From start of treatment through to death or study completion (last recorded date on which the subject was known to be alive), whichever occurs first, approximately 18 months.
Secondary outcome [29] 0 0
PD of AZD8421 (M1B only)
Timepoint [29] 0 0
From start of treatment, at predefined intervals throughout the administration of AZD8421 until end of treatment, approximately 18 months.

Eligibility
Key inclusion criteria
* 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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.
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/12/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
18/06/2025
Actual
Sample size
Target
204
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - East Melbourne
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Missouri
Country [2] 0 0
United States of America
State/province [2] 0 0
Rhode Island
Country [3] 0 0
United States of America
State/province [3] 0 0
Tennessee
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Korea, Republic of
State/province [5] 0 0
Seoul
Country [6] 0 0
Spain
State/province [6] 0 0
Barcelona
Country [7] 0 0
Spain
State/province [7] 0 0
Pamplona
Country [8] 0 0
Spain
State/province [8] 0 0
Valencia
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Cambridge
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Leeds
Country [11] 0 0
United Kingdom
State/province [11] 0 0
London
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Richard Baird, MD, PhD
Address 0 0
Cambridge University Hospitals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available to whom?
When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06188520