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

NCT06188520 | Recruiting Phase 1 FDA Drug

• 1 other identifier: D8470C00001
• Study Type: interventional
• Target: 564
• Locations: 5 countries
• Sites: 14

Brief 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.

Conditions

ER+ HER2- Advanced Breast Cancer; High-grade Serous Ovarian Cancer (HGSOC)

Outcome Measures

Primary Outcomes (4)

• Incidence of dose limiting toxicities (DLTs) as defined in the protocol.

  Percentage of participants with incidence of DLTs.

  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.

  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.

  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.

  From start of treatment until the end of safety follow-up, approximately 18 months.

Secondary Outcomes (30)

• Overall Response Rate (ORR)

  8 weeks from start of treatment until end of treatment or objective disease progression, approximately 18 months.

• Duration of Response (DoR)

  8 weeks from start of treatment until end of treatment or objective disease progression, approximately 18 months.

• Disease control rate (DCR)

  24 weeks after the start of treatment.

• Percentage change in tumor size

  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)

  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.

Study Arms (2)

Module 1

EXPERIMENTAL

AZD8421 monotherapy

Drug: AZD8421

Module 2A

EXPERIMENTAL

AZD8421 with camizestrant and CDK4/6 inhibitor

Drug: AZD8421; Drug: Camizestrant; Drug: Ribociclib; Drug: Palbociclib; Drug: Abemaciclib

Interventions

AZD8421 DRUG

CDK2 inhibitor

Module 1; Module 2A

Camizestrant DRUG

SERD

Also known as: AZD9833

Module 2A

Ribociclib DRUG

CDK4/6 inhibitor

Also known as: Kisqali

Module 2A

Palbociclib DRUG

CDK4/6 inhibitor

Also known as: Ibrance

Module 2A

Abemaciclib DRUG

CDK4/6 inhibitor

Also known as: Verzenios

Module 2A

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (14)

Research Site

St Louis, Missouri, 63141, United States

RECRUITING

Research Site

Providence, Rhode Island, 02903, United States

RECRUITING

Research Site

Nashville, Tennessee, 37201, United States

RECRUITING

Research Site

Houston, Texas, 77030, United States

RECRUITING

Research Site

East Melbourne, 3002, Australia

RECRUITING

Research Site

Seoul, 03722, South Korea

RECRUITING

Research Site

Seoul, 06351, South Korea

RECRUITING

Research Site

Barcelona, 8035, Spain

RECRUITING

Research Site

Pamplona, 31005, Spain

RECRUITING

Research Site

Valencia, 46010, Spain

RECRUITING

Research Site

Cambridge, CB2 0XY, United Kingdom

RECRUITING

Research Site

Leeds, LS9 7TF, United Kingdom

RECRUITING

Research Site

London, EC1A 7BE, United Kingdom

RECRUITING

Research Site

Manchester, M20 4BX, United Kingdom

RECRUITING

MeSH Terms

Interventions

AZD9833; ribociclib; palbociclib; abemaciclib

Study Officials

• Richard Baird, MD, PhD

  Cambridge University Hospitals

  STUDY CHAIR

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2023
• First Posted: January 3, 2024
• Study Start: December 5, 2023
• Primary Completion (Estimated): August 4, 2027
• Study Completion (Estimated): August 4, 2027
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 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.
• Access Criteria: 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.

Locations

AU (1); KR (2); US (4); GB (4); ES (3)