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.
- Conditions
- Patients with ER+ HER2- advanced breast cancer and patients with high-grade serious ovarian cancer (HGSOC)Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-507305-33-00
- Lead Sponsor
- Astrazeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 204
Participant must be 18 years of age or more at the time of signing the informed consent form., Provision of consent to enable submission of archival tumor tissue, and availability of appropriate tissue., Participants must be female., 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 by CT, MRI, or plain X-ray, or clinical examination. Blastic-only lesions in bone are not considered assessable., Female participants of childbearing potential must agree to use one highly effective contraceptive measure., Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol., Provision of signed and dated written optional genetic research information informed consent prior to collection of samples for optional genetic research that supports the Genomic Initiative.
Intervention with any of the following: a. Any cytotoxic chemotherapy, investigational agents, or other anticancer 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). Chemowarhead ADCs are considered to be myelosuppressive in this context. b. 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 2 weeks or 5 half-lives (whichever is longer) prior to first dose of IMP and withheld throughout the study until 2 weeks after the last dose of study drug, excluding CDK4/6is under study. c. Participants must be excluded who are unable to comply with the prohibited concomitant medication restrictions specific to each module of study. Drugs that have a known risk of Torsades de Pointes, as indicated in CredibleMeds® list (www.crediblemeds.org). d. Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of IMP, with the exception of participants receiving radiation to more than 30% of the bone marrow or a wide field of radiation within 4 weeks of the first dose of IMP. e. Major surgical procedure or significant traumatic injury, as judged by the Investigator, 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, Inability to swallow oral medications., 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, which in the Investigator's opinion makes it undesirable for the participant to participate in the study or which would jeopardize compliance with the protocol, 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: a. Mean resting QTcF > 470 msec obtained from a triplicate ECG b. 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. c. Any clinically significant 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. d. LVEF < 50%, and/or experience of any of the following procedure
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method