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Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies

ConditionAdvanced Solid Malignancies
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-130
SponsorAstraZeneca

About this trial

This study will assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of AZD9574 individually and in combination with anti-cancer agents in participants with advanced cancer that has recurred/progressed.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Eastern Cooperative Oncology Group performance status (ECOG PS) with no deterioration over the previous 2 weeks.

Progressive cancer at the time of enrollment.

Adequate organ and marrow function.

Must have evaluable disease.

Disqualifiers

Major surgery within 4 weeks of the first dose of study intervention.

Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study intervention.

With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study intervention.

Any known history of persisting severe pancytopenia due to any cause.

Trial design

Design model

Sequential

Treatments tested in this trial

  • AZD9574

    Drug

    Participants will receive AZD9574 orally.

  • Temozolomide (TMZ)

    Drug

    Participants will receive temozolomide orally.

  • [11C]AZ1419 3391

    Drug

    Participants will receive \[11C\]AZ1419 3391 intravenously.

  • Trastuzumab Deruxtecan (T-DXd)

    Drug

    Participants will receive T-DXd intravenously.

  • Datopotamab Deruxtecan (Dato-DXd)

    Drug

    Participants will receive Dato-DXd intravenously.

Treatment groups

695 Participants
are divided into 9 treatment groups

9

Treatment groups

See each treatment group below.

Group A: Module 1 Part A: Dose escalationExperimental treatment 1 intervention
Group B: Module 1 Part B: Dose expansionExperimental treatment 1 intervention
Group C: Module 2 Part A: Dose escalationExperimental treatment 2 interventions
Group D: Module 3 Panel 1: AZD9574 monotherapy (Sweden only)Experimental treatment 2 interventions
Group E: Module 3 Panel 2: AZD9574 + TMZ (Sweden only)Experimental treatment 3 interventions
Group F: Module 3 Panel 3: AZD9574 monotherapy (Sweden only)Experimental treatment 2 interventions
Group G: Module 4 Part A: Dose escalation (AZD9574 + T-DXd)Experimental treatment 2 interventions
Group H: Module 4 Part B : Dose expansion (AZD9574 + T-DXd)Experimental treatment 2 interventions
Group I: Module 5 Part A : Dose escalation (AZD9574 + Dato-DXd)Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Incidence of Adverse Events (AEs), and Serious Adverse Events (SAEs)

The safety and tolerability of AZD9574 as monotherapy and in combination with anti-cancer agents and TMZ in participants with advanced malignancies will be assessed.

Time frame
From first dose to post-treatment follow-up (approximately three years)
2

Changes from baseline in laboratory findings, electrocardiograms (ECGs), and vital signs

The safety and tolerability of AZD9574 as monotherapy and in combination with anti-cancer agents and TMZ in participants with advanced malignancies will be assessed.

Time frame
From last assessment prior to first dose to post-treatment follow up visit (approximately three years)
3

Change from baseline Eastern Cooperative Oncology Group performance status (ECOG PS)

The performance status of ECOG will be assessed based on an ECOG grade of 0 to 4 where '0' is a high grade while '4' is a low grade. An ECOG grade of '0' means that the participant is fully active, able to carry on all pre-disease performance without restriction. An ECOG grade of '4' means that the participant is completely disabled, cannot carry on any self-care, and is totally confined to a bed or chair.

Time frame
From last assessment prior to first dose to post-treatment follow up visit (approximately three years)
4

Incidence of Dose Limiting Toxicities (DLTs)

The safety and tolerability of AZD9574 as monotherapy and in combination with anti-cancer agents in participants with advanced malignancies will be assessed at each dose level.

Time frame
Cycle 0 and Cycle 1 (Day 1 to Day 35)

Secondary outcomes

1

Area Under the Curve (AUC)

The AUC of AZD9574 following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents will be evaluated.

Time frame
Cycle 0, Cycle 1 Day 1, Cycle 1 Day 16 (Cycle 0 = 7 days; Cycle 1 = 28 days)
2

Maximum plasma concentration (Cmax)

The Cmax of AZD9574 following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents will be evaluated.

Time frame
Cycle 0, Cycle 1 Day 1, Cycle 1 Day 16 (Cycle 0 = 7 days; Cycle 1 = 28 days)
3

Time taken to reach maximum plasma concentration (tmax)

The tmax of AZD9574 following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents will be evaluated.

Time frame
Cycle 0, Cycle 1 Day 1, Cycle 1 Day 16 (Cycle 0 = 7 days; Cycle 1 = 28 days)
4

Minimum plasma concentration at steady state (Cmin,ss)

The Cmin,ss of AZD9574 following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents will be evaluated.

Time frame
Cycle 0, Cycle 1 Day 1, Cycle 1 Day 16 (Cycle 0 = 7 days; Cycle 1 = 28 days)

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

AstraZeneca

Lead sponsor

Source ClinicalTrials.gov
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