A study to test the safety and efficacy of a new drug, AZD3470, in patients with advanced solid tumours.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astrazeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Nov 2024 → ongoing

Decision date (initial)

2024-04-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenetic, Pharmacodynamic, Therapy, Safety, Pharmacokinetic, Dose response, Pharmacogenomic

To assess the safety and tolerability, and to determine the RP2D of AZD3470 as monotherapy and in combination with anti-cancer agents in participants with MTAP deficient advanced solid tumors.

Secondary objectives 3

1. To estimate the antitumor activity of AZD3470 as monotherapy and in combination with anticancer agents.
2. To characterise the PK following multiple, oral doses of AZD3470 administered as a monotherapy.
3. To evaluate the effect of multiple doses of AZD3470 on pharmacokinetics of single oral dose of midazolam and/or dextromethorphan.

Conditions and MedDRA coding

Advanced/metastatic solid tumors that are MTAP deficient.

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 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.
2. Willing to provide archival and/or baseline tumor sample to meet the minimum tissue requirement for central MTAP deficiency testing.
3. Participants must have received and progressed, are refractory or are intolerant to standard therapy for the specific tumor type. All participants are required to have had at least one prior line of treatment in the recurrent or metastatic setting.
4. MTAP deficient tumors defined as evidence of homozygous deletion of one or more exons of the MTAP gene in tumor tissue AND/OR loss of MTAP expression in the tumor tissue.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
6. A minimum life expectance of 12 weeks in the opinion of the Investigator.
7. Participants must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
8. Adequate organ and bone marrow reserve function.
9. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion criteria 2

1. Spinal cord compression or symptomatic and unstable brain metastases or leptomeningeal disease or primary malignancies of the central nervous system. - Allogeneic organ transplantation. - Any significant laboratory finding or any severe and uncontrolled medical condition - Any of the following cardiac criteria: - LVEF ≤ 50%, prior or current cardiomyopathy - clinically active cardiovascular disease, or a history of myocardial infarction within the last 6 months - uncontrolled Angina or acute coronary syndrome within 6 months - severe valvular heart disease - uncontrolled hypertension - risk of brain perfusion problems, stroke or transient ischemic attack in the last 6 months, undergone coronary artery bypass graft, angioplasty or vascular stent - chronic heart failure - factors that increase the risk of QTc prolongation or risk of arrhythmic events - Mean resting QTcF > 470 msec or any clinically important abnormalities in rhythm
2. Use of therapeutic anti-coagulation for treatment of acute thromboembolic events. - Serologic active hepatitis B or C infection. - Known to have tested positive for Human immunodeficiency virus (HIV). - Confirmed or suspected ILD/pneumonitis or history of (non-infectious) ILD/pneumonitis that required oral or IV steroids or supplemental oxygen - Active gastrointestinal disease or other condition that would interfere with oral therapy. - History of another primary malignancy. - Unresolved toxicities from prior anti-cancer therapy, except alopecia and neuropathy. - Prior treatment with a protein arginine methyltransferase 5 (PRMT5) inhibitor.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Incidence of adverse events (AEs) determined by the number of patients with adverse events by system organ class and preferred term.
2. Incidence of serious adverse events (SAEs) determined by the number of patients with adverse events by system organ class and preferred term.
3. Incidence of dose-limiting toxicities (DLT) as determined by number of patients with at least 1 dose-limiting toxicity (DLT) as defined by the clinical study protocol

Secondary endpoints 8

1. Radiological response assessed by the Investigator evaluated according to RECIST v1.1 1. Objective response rate (ORR) - The percentage or number of participants who have a confirmed investigator assessed complete or partial response as determined by the investigator according to response criteria in solid tumors (RECIST v1.1).
2. Duration of response (DOR) - the time from date of first documented objective response (which is subsequently confirmed) until date of documented disease progression per Tumor RECIST v1.1 as assessed by the Investigator at local site or death due to any cause.
3. Disease Control Rate (DCR) at 12 weeks- defined as the percentage of participants who have a confirmed CR or PR or who have SD per RECIST 1.1 as assessed by the Investigator at local site and derived from the raw tumor data for at least 11 weeks after date of first dose to allow for an early assessment within the assessment window.
4. Best percentage change in tumor size - Percentage change from baseline in TL (target lesion) tumor-size is based on the RECIST 1.1 TL measurements as assessed by the Investigator.
5. Progression Free Survival (PFS) - defined as time from date of first dose (nonrandomized study parts) or date of randomization (randomized study parts) until progression per RECIST v1.1 as assessed by the Investigator at local site, or death due to any cause.
6. Overall Survival (OS) - defined as time from date of first dose (nonrandomized study parts) or date of randomization (randomized study parts) until the date of death due to any cause.
7. Module 1 Endpoints Part A (Dose escalation) Measurement of PK parameters: Area under the concentration time curve (AUC), maximum observed plasma concentration of the study drug (Cmax), Time to maximum observed plasma concentration of the study drug (T-max), Terminal elimination half-life (t 1/2), amount of AZD3470 excreted in urine (Ae), renal clearance (Clr)
8. (USA ONLY) Module 1 Endpoints Part A (DDI) - Plasma geometric mean ratio (Cmax and AUC) of Midazolam evaluated with and without AZD3470 - Plasma geometric mean ratio (Cmax and AUC) of Dextromethorphan evaluated with and without AZD3470 - Percentage change from baseline tumor SDMA as measured by immunohistochemistry.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astrazeneca AB

Sponsor organisation

Astrazeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

Astrazeneca AB

Contact name

Clinical Study Information Centre

Public contact point

Organisation

Astrazeneca AB

Contact name

Clinical Study Information Centre

Locations

3 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 27 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications