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RecruitingLast updated: 19 January 2024

CYCAD-1: This study is evaluating a new drug (called AZD8421) alone and in combination with selected targeted anti-cancer drugs in people with ER+, HER- advanced breast cancer, and people with metastatic high-grade serious ovarian cancerA 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

Clinical summary

Summary

This study has two modules: M1 and M2.

Cohort M1 (monotherapy), will evaluate how safe and tolerable a new drug called AZD8421 is when given alone, and will identify a recommended phase 2 dose (RP2D) in people with ER+ HER- advanced breast cancer who have previously been treated with 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 will also be evaluated as a combination therapy in M2. In M2, AZD8421 will be administered with a CDK4/6 inhibitor - one or more of abemaciclib, ribociclib and palbociclib and camizestrant (a next generation oral SERD) - in people with ER+ HER- advanced breast cancer who have previously been treated with a CDK4/6 inhibitor. 

Conditions

This trial is treating patients with ER+/HER- advanced breast cancer and metastatic high-grade serous ovarian cancer

Cancer

Multi-Cancer Multi-Cancer

Age

People18+

Phase

I/II

Trial Acronym

CYCAD-1

More information

Trial Identifiers

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Trial sponsor

AstraZeneca

Scientific 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

Eligibility

Inclusion

  • 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.

Exclusion

  • 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.

Inclusion

  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • You have had treatment, but your cancer has come back.
  • Your cancer has not spread to other parts of the body.
  • Your cancer has spread to other parts of the body.

Exclusion

  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria.

Ask your doctor if this trial could be right for you.

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