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Testing AZD3470 in patients with advanced solid tumors lacking MTAP.

PRIMROSE: A Modular Phase I/IIa, Multi-centre, Dose Escalation, and Expansion Study of AZD3470, a MTA Cooperative PRMT5 Inhibitor, as Monotherapy and in Combination With Anticancer Agents in Participants With Advanced/Metastatic Solid Tumors That Are MTAP Deficient

Phase1; Phase2 Interventional AstraZeneca · NCT06130553

This study is testing a new drug called AZD3470 to see if it can help people with advanced solid tumors that lack a specific protein and who haven't had success with other treatments.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment334 (estimated)
Ages18 Years and up
SexAll
SponsorAstraZeneca Industry-sponsored
Drugs / interventionsradiation
Locations20 sites (San Francisco, California and 19 other locations)
Trial IDNCT06130553 on ClinicalTrials.gov

What this trial studies

This is a first-time-in-human, open-label, multi-center study evaluating the safety and efficacy of AZD3470, a PRMT5 inhibitor, in patients with advanced or metastatic solid tumors that are deficient in MTAP. The study is structured in modules, starting with dose escalation and optimization, and may include combination treatments based on emerging data. Participants will provide tumor samples for testing and must have previously received standard therapies without success.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with advanced solid tumors that show MTAP deficiency and have progressed after at least one prior line of treatment.

Not a fit: Patients with solid tumors that do not exhibit MTAP deficiency or those who have not received prior treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with MTAP deficient tumors who have limited treatment alternatives.

How similar studies have performed: While this approach is novel in targeting MTAP deficient tumors, similar studies with other targeted therapies have shown promising results.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria (All Modules) Participants are ≥ 18 years (or the legal age of consent in the jurisdiction) at the time of signing the informed consent form.

Participants are able to provide written informed consent and are willing and able to comply with study procedures.

Participants are willing to provide archival and/or newly obtained (baseline) tumor tissue for central testing, including required biomarker assessment(s) (and any module-specific biomarker requirements).

Participants have tumors meeting the protocol-defined MTAP-deficiency requirement, based on acceptable prior testing and/or central testing per protocol.

Participants have received prior systemic therapy appropriate for the tumor type and disease stage and have disease progression on or after prior therapy; participants must have had ≥ 1 prior line of systemic treatment in the recurrent/metastatic (advanced) setting.

Participants have ECOG performance status 0-1. Participants have life expectancy ≥ 12 weeks, in the opinion of the Investigator.

Participants have measurable disease per RECIST v1.1. Participants have adequate organ and bone marrow function per protocol-defined laboratory/assessment criteria.

Participants have a treatment-free interval ≥ 3 weeks from prior anticancer therapy before starting study drug (with any additional protocol-defined washout requirements for certain therapies/procedures).

Contraception use by men and women is consistent with local regulations and protocol-defined requirements.

Additional Inclusion Criteria (Module 2: Non-squamous NSCLC) Participants have histologically or cytologically confirmed non-squamous NSCLC, Stage IIIB/IIIC not amenable to curative therapy or Stage IV.

Participants have documented radiographic extracranial disease progression while on or after the most recent treatment regimen for advanced/metastatic NSCLC (CNS-only progression is not eligible).

NSCLC of mixed histology is allowed if not predominantly squamous; no small cell or large cell neuroendocrine components.

Participants meet one of the following:

Tumor has a documented EGFR alteration eligible for EGFR-directed therapy (per protocol-defined criteria) and the participant has received prior systemic therapy appropriate for EGFR-altered advanced/metastatic NSCLC (per protocol), OR Tumor is negative for EGFR alterations eligible for EGFR-directed therapy, has no other known actionable genomic alterations for which locally approved/available targeted therapies exist (per protocol-defined criteria), meets any additional protocol-required biomarker criteria for this cohort (as applicable), and the participant has received prior systemic therapy appropriate for non-actionable-alteration advanced/metastatic NSCLC (per protocol).

Exclusion Criteria (All Modules) Participants have spinal cord compression, or symptomatic and unstable brain metastases, leptomeningeal disease, or primary CNS malignancy. Participants with asymptomatic, radiographically stable brain metastases who do not require steroids (or who have completed definitive therapy and are neurologically stable off steroids, per protocol) may be eligible.

Participants have a history of allogeneic organ transplantation. Participants have any clinically significant abnormal laboratory finding or severe and uncontrolled medical condition that, in the Investigator's opinion, makes participation unsafe, including active infection requiring systemic treatment.

Participants have clinically significant cardiovascular disease or risk factors (including reduced LVEF, cardiomyopathy, clinically active cardiovascular disease, recent major ischemic events or revascularization procedures, uncontrolled angina, severe valvular disease, uncontrolled hypertension, clinically significant heart failure, or recent stroke/TA clinically significant ECG abnormalities, prolonged QTc, or conditions/medications that increase risk of QTc prolongation or arrhythmic events)..

Participants require therapeutic anticoagulation for treatment of acute thromboembolic events, per protocol.

Participants have active hepatitis B or hepatitis C infection (including detectable viral load, per protocol-defined testing).

Participants have known HIV infection. Participants have current ILD/pneumonitis, or a history of (non-infectious) ILD/pneumonitis requiring systemic steroids or supplemental oxygen, or suspected ILD/pneumonitis that cannot be ruled out by screening imaging.

Participants have active gastrointestinal disease, malabsorption, or other GI condition/surgery that would significantly interfere with oral drug absorption or tolerability.

Participants have a history of another primary malignancy. Participants have unresolved clinically significant toxicity from prior anticancer therapy (typically Grade ≥ 2).

Participants have had prior treatment with a PRMT5 inhibitor Participants are pregnant, breastfeeding, or intend to become pregnant during study participation.

Additional Exclusion Criteria (Module 2 Only) Participants have inaccessible veins and/or inability to place required venous access (e.g., port), per Investigator judgment.

Participants have contraindication to required CNS imaging (brain MRI preferred or CT with contrast).

Participants have clinically significant corneal disease. Participants have known active tuberculosis infection, per clinical evaluation and local practice.

Participants have significant third-space fluid (e.g., pleural effusion/ascites) not amenable to required repeated drainage, per Investigator judgment.

Participants have severe pulmonary function compromise due to intercurrent pulmonary illness (e.g., severe COPD/asthma/restrictive lung disease, recent pulmonary embolism), per protocol.

Participants have recent radiotherapy that does not meet protocol-defined washout requirements and/or ongoing radiation-related toxicities requiring corticosteroids.

Participants have had prior treatment with protocol-prohibited anticancer therapies.

Where this trial is running

San Francisco, California and 19 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Advanced Solid Tumors That Are MTAP Deficientsolid tumorMTAP deficient
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.