What side effects are associated with this type of intervention?

Common treatments for solid tumors, including those targeting MTAP deficiency pathways like AZD3470, often result in a range of side effects. These can include hematologic toxicities such as neutropenia and anemia, gastrointestinal issues like nausea and diarrhea, and general fatigue. Targeted therapies may also cause specific side effects such as hypertension and hypothyroidism due to their antiangiogenic properties. 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 for the treatment of solid tumors, focusing on specific genetic mutations and pathways. For instance, pembrolizumab and nivolumab are immune checkpoint inhibitors approved for various solid tumors, including melanoma and non-small cell lung cancer. Additionally, drugs like olaparib and rucaparib, which are PARP inhibitors, have been approved for BRCA-mutated ovarian and breast cancers. While specific FDA approvals for drugs targeting MTAP deficiency in solid tumors are not detailed, the ongoing study of AZD3470 represents a promising approach in this area, aiming to exploit the vulnerabilities in cancer cells with MTAP deficiency.

What other types of research exist?

Promising alternatives to AZD3470 for solid tumors with MTAP deficiency include ZEN-3694 in combination with enzalutamide, which has shown potential efficacy in metastatic castration-resistant prostate cancer, and AZD5305, a next-generation PARP1 inhibitor, which has demonstrated potent antiproliferative activity and selectivity for DNA repair-deficient cells in preclinical models.

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PRMT5 Inhibitor

AZD3470 for Advanced Solid Cancers (PRIMROSE 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

Participant must be at least 18 years of age or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the ICF.

Participants must have received and progressed, are refractory or are intolerant to standard therapy for the specific tumour type. All participants are required to have had at least one prior line of treatment in the recurrent or metastatic setting.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from date of first dose of azd3470 up until the date of death due to any cause (approximately 2 years).

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called AZD3470 in patients with advanced cancers that have a specific genetic issue. The goal is to see if the drug is safe, well-tolerated, and effective in stopping or slowing down cancer growth. AZD3470 is being tested for its potential to treat cancers with this genetic issue, which has been linked to a dependency on a specific protein, making it a target for new cancer therapies.

Who is the study for?

This trial is for adults with advanced or metastatic solid tumors that lack MTAP, a specific gene. Participants must have tried standard treatments without success and should be in fairly good health (able to perform daily activities with ease or some limitation). They need at least one tumor that can be measured by medical scans and should expect to live at least 12 more weeks.

What is being tested?

The study tests AZD3470, a new drug targeting PRMT5 enzymes in patients whose tumors don't have the MTAP gene. It's an early-phase trial assessing how safe the drug is, how well it's tolerated, its pharmacokinetics (how it moves through the body), effects on the body, and initial signs of effectiveness.

What are the potential side effects?

Since this is a first-in-human study for AZD3470, detailed side effects are not yet known. However, participants may experience typical cancer treatment-related side effects such as fatigue, nausea, changes in blood counts leading to increased infection risk or bleeding problems.

Eligibility Criteria

Inclusion Criteria

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

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I am at least 18 years old or the legal age of consent where the study is conducted.

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My cancer has not responded to or I cannot tolerate the standard treatment, and I have had at least one treatment for it when it came back or spread.

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My tumor lacks MTAP due to gene deletion or no MTAP protein expression.

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I am fully active or can carry out light work.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from date of first dose of azd3470 up until the date of death due to any cause (approximately 2 years).

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from date of first dose of azd3470 up until the date of death due to any cause (approximately 2 years).

This trial's timeline: 3 weeks for screening, Varies for treatment, and from date of first dose of azd3470 up until the date of death due to any cause (approximately 2 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

Incidence of adverse events (AEs) and serious adverse events (SAEs)

Incidence of dose-limiting toxicities (DLT)

Secondary study objectives

Module 1 Endpoints Part A (DDI) - Measurement of PK parameters of Dextromethorphan: AUC

Module 1 Endpoints Part A (DDI) - Measurement of PK parameters of Dextromethorphan: Cmax

Module 1 Endpoints Part A (DDI) - Measurement of PK parameters of Midazolam: AUC

+13 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: AZD3470 MonotherapyExperimental Treatment1 Intervention

Part A dose escalation and back-fill cohorts and Part B dose optimization and expansion cohorts of varying doses of AZD3470

0 / 4Eligibility 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

The most common treatments for solid tumors include chemotherapy, immunotherapy, and targeted therapies. Targeted therapies, such as PRMT5 inhibitors like AZD3470, specifically inhibit enzymes or pathways crucial for tumor survival and growth. For instance, PRMT5 inhibitors block the PRMT5 enzyme, which is essential for the survival of MTAP-deficient tumors, leading to tumor growth inhibition. This precision in targeting specific cancer pathways is particularly important for solid tumor patients as it can result in more effective treatments with fewer side effects compared to traditional chemotherapy, thereby improving patient outcomes.