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

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

Trial statusRecruiting

Trial phasePhase 1, Phase 2

Trial typeInterventional

Biological sexFemale

Age18+

SponsorAstraZeneca

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

AZD8421
Drug
CDK2 inhibitor
Camizestrant
Drug
SERD
Ribociclib
Drug
CDK4/6 inhibitor
Palbociclib
Drug
CDK4/6 inhibitor
Abemaciclib
Drug
CDK4/6 inhibitor

Treatment groups

564 Participants

are divided into 2 treatment groups

Group A: Module 1Experimental treatment 1 intervention

Group B: Module 2AExperimental treatment 5 interventions

Trial outcomes

Primary outcomes

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

Percentage of participants with incidence of DLTs.

Time frame

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.

Time frame

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.

Time frame

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.

Time frame

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

Secondary outcomes

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.

Time frame

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).

Time frame

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.

Time frame

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

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.