What is the mechanism of action of this treatment?

Common treatments for solid tumors, particularly targeted therapies and novel agents like AZD9574, work by interfering with specific molecular pathways essential for cancer cell growth and survival. These therapies may inhibit proteins involved in cell signaling, such as tyrosine kinases, or disrupt processes like DNA repair and cell division. For example, tyrosine kinase inhibitors block signals that promote tumor growth, while PARP inhibitors prevent cancer cells from repairing DNA damage. This targeted approach is significant for solid tumor patients as it allows for more personalized treatment, potentially improving efficacy and reducing side effects compared to conventional chemotherapy.

What side effects are associated with this type of intervention?

Common treatments for solid tumors, especially targeted therapies and novel agents like those being studied in the AZD9574 trial, often have side effects that include fatigue, nausea, diarrhea, and skin rashes. Additionally, these therapies can cause more specific toxicities such as hypertension, hypothyroidism, and cardiovascular effects. Hematologic toxicities like anemia, neutropenia, and thrombocytopenia are also frequently observed. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several targeted therapies and novel agents for the treatment of solid tumors. For instance, pembrolizumab, an immune checkpoint inhibitor, has been approved for various solid tumors, including melanoma and non-small cell lung cancer. Additionally, the combination of dabrafenib and trametinib, which targets the BRAFV600E mutation, has shown efficacy in tumors with this specific mutation. These treatments exemplify the ongoing advancements in targeted therapies aimed at improving outcomes for patients with solid tumors.

What other types of research exist?

Promising alternatives to AZD9574 for solid tumor patients include: <ol> <li>Pembrolizumab (Keytruda) - an immune checkpoint inhibitor showing efficacy in various solid tumors.</li> <li></li> </ol> Nivolumab (Opdivo) - another immune checkpoint inhibitor effective in multiple solid tumors. 3. Atezolizumab (Tecentriq) - an immune checkpoint inhibitor used in combination with bevacizumab for renal cell carcinoma. 4. Cabozantinib - a tyrosine kinase inhibitor showing promise in advanced renal cell carcinoma and other solid tumors. 5. Regorafenib - a multikinase inhibitor effective in metastatic colorectal cancer and other solid tumors. 6. Savolitinib - a MET inhibitor showing efficacy in papillary renal cell carcinoma.

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AZD9574 for Advanced Solid Tumors (CERTIS1 Trial)

Phase 1 & 2

Recruiting

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants must have progressed following at least one prior systemic treatment for metastatic or advanced disease and have no satisfactory alternative treatment option

Participants must have one of the following: Histologically or cytologically confirmed relapsed advanced ovarian, fallopian tube or primary peritoneal cancer and evidence of a predicted loss of function germline or tumour mutation in one of the following homologous recombination repair genes: BRCA1, BRCA2, PALB2, RAD51C or RAD51D; Histologically or cytologically confirmed HER2-negative carcinoma of the breast with recurrent locally advanced or metastatic disease and evidence of a predicted loss of function germline or tumour mutation in one of the following homologous recombination repair genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D; Histologically or cytologically confirmed advanced/metastatic castration-resistant prostate cancer (CRPC) and evidence of a predicted loss of function germline or tumour mutation in one of the following homologous recombination repair genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D; Histologically or cytologically confirmed advanced/metastatic pancreatic cancer and evidence of a predicted loss of function germline or tumour mutation in one of the following homologous recombination repair genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D

Must not have

History of severe brain injury or stroke

Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD9574

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from baseline to every 8 weeks until objective disease progression (approximately three years)

Awards & highlights

No Placebo-Only Group

Summary

This trial tests AZD9574, a new drug that stops cancer cells from repairing themselves. It targets patients with advanced or relapsed cancers who need new treatment options. The drug is tested alone and in combination with other cancer-fighting drugs.

Who is the study for?

This trial is for adults with advanced solid tumors that have worsened despite previous treatments. They must be in stable condition, not planning to conceive, and have specific genetic mutations related to cancer growth. People who've had certain prior therapies or severe reactions to similar drugs, uncontrolled diseases, or are unable to take oral medications cannot join.

What is being tested?

The study tests AZD9574 alone and combined with other anti-cancer agents (Trastuzumab Deruxtecan, Datopotamab Deruxtecan, Temozolomide) on 490 participants. It aims to evaluate safety and early signs of effectiveness while monitoring how the body processes these drugs.

What are the potential side effects?

Potential side effects include typical drug reactions like nausea and fatigue but may also involve more serious issues such as blood disorders or allergic responses due to the investigational nature of AZD9574 and its combinations.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My condition worsened after treatment for advanced cancer and I have no other good treatment options.

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I have advanced cancer with a specific gene mutation.

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My breast cancer is HER2-negative with a specific genetic mutation.

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My brain tumor has an IDH1 or IDH2 mutation.

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My cancer is getting worse.

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I am fully active or can carry out light work.

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My physical health hasn't worsened in the last 2 weeks.

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I have at least one cancer lesion that hasn't been treated with radiation or has grown after radiation.

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My cancer can be measured or observed.

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My cancer cannot be removed by surgery or has spread to other parts of my body.

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I can provide a tissue sample from my tumor for testing.

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I am a woman who can have children and have tested negative for pregnancy.

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I have a tumor larger than 10mm that hasn't been treated with radiation.

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My cancer has worsened after radiation and one chemotherapy treatment.

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I have a tumor larger than 10mm that hasn't been treated with radiation.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had a severe brain injury or stroke.

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I cannot take AZD9574 due to severe nausea, vomiting, gut diseases, swallowing issues, or major bowel surgery.

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I cannot have MRI with gadolinium or cannot keep my steroid dose stable.

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I am not currently on any cancer treatments or prohibited medications.

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I am prone to bleeding easily.

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I have a history of severe low blood cell counts.

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I have not had any serious illnesses in the last year.

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I have been diagnosed with MDS, AML, or have symptoms suggesting these conditions.

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I have not had major surgery in the last 4 weeks.

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I have a history of cancer.

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My spinal cord compression is stable, treated, and I haven't needed high-dose steroids for over 4 weeks.

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I have had a condition where my lymphocytes grow abnormally.

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I do not have severe illnesses or infections like HIV or hepatitis.

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I do not have uncontrolled seizures or take more than 2 seizure medications.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ first documented response until the date of documented progression or end of study (approximately three years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~first documented response until the date of documented progression or end of study (approximately three years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and first documented response until the date of documented progression or end of study (approximately three years) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

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

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

+1 more

Secondary study objectives

Accumulation ratio

Area Under the Curve (AUC)

Dose proportionality

+67 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

8Treatment groups

Experimental Treatment

Group I: Module 5 Part A : Dose escalation (AZD9574 + Dato-DXd)Experimental Treatment2 Interventions

Participants with advanced, unresectable, or metastatic solid tumours in different types of cancers will receive a combination of AZD9574 and Dato-DXd at escalating cohorts.

Group II: Module 4 Part A: Dose escalation (AZD9574 + T-DXdat)Experimental Treatment2 Interventions

Participants with advanced, unresectable, or metastatic solid tumours that are HER2-positive will receive a combination of AZD9574 and T-DXdat at escalating cohorts.

Group III: Module 3 Panel 3: AZD9574 monotherapy (Sweden only)Experimental Treatment1 Intervention

Participants with breast cancer (without BM).

Group IV: Module 3 Panel 2: AZD9574 + TMZ (Sweden only)Experimental Treatment1 Intervention

Participants with IDH 1/2-mutant glioma who are PARPi naive will receive AZD9574 and TMZ at escalating cohorts.

Group V: Module 3 Panel 1: AZD9574 monotherapy (Sweden only)Experimental Treatment1 Intervention

Participants with advanced/relapsed HER2-negative breast, ovarian, prostate, or pancreatic cancer and expressing BRCA1m, BRCA2m, PALB2m, RAD51Cm or RAD51Dm.

Group VI: Module 2 Part A: Dose escalationExperimental Treatment2 Interventions

Participants with IDH 1/2-mutant glioma who are PARPi naive will receive AZD9574 and TMZ at escalating cohorts.

Group VII: Module 1 Part B: Dose expansionExperimental Treatment1 Intervention

Participants with breast cancer who are PARPi naive at doses determined in dose-escalation.

Group VIII: Module 1 Part A: Dose escalationExperimental Treatment1 Intervention

Participants with advanced/relapsed ovarian, breast, pancreatic, or prostate cancer who are deemed suitable for a PARPi will receive AZD9574 monotherapy at escalating cohorts.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Temozolomide

2010

Completed Phase 3

~1880

0 / 29Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for solid tumors, particularly targeted therapies and novel agents like AZD9574, work by interfering with specific molecular pathways essential for cancer cell growth and survival. These therapies may inhibit proteins involved in cell signaling, such as tyrosine kinases, or disrupt processes like DNA repair and cell division. For example, tyrosine kinase inhibitors block signals that promote tumor growth, while PARP inhibitors prevent cancer cells from repairing DNA damage. This targeted approach is significant for solid tumor patients as it allows for more personalized treatment, potentially improving efficacy and reducing side effects compared to conventional chemotherapy.

Moving Synergistically Acting Drug Combinations to the Clinic by Comparing Sequential versus Simultaneous Drug Administrations.