Advanced MalignanciesPhase 1/2NCT03907969

A Clinical Trial to Evaluate AZD7648 Alone and in Combination With Other Anti-cancer Agents in Patients With Advanced Cancers.

A Phase 1/2 study testing AZD7648 and PLD in people with Advanced Malignancies, run by AstraZeneca at 5 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

This is a modular Phase I/IIa, open-label, multi-centre, study of AZD7648 administered orally, either as a monotherapy, or in combination with either cytotoxic chemotherapies or novel anti-cancer agents in participants with advanced malignancies. Read more about this study

Who is it for?: Ages 18 to 130 years
Conditions the study is for: Advanced Malignancies
What is being tested?: AZD7648 and PLD
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: 5 sitesin 2 countries
Study dates: 9 Oct 2019to 7 Dec 2022
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 130 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Capable and willing to give signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF).
Participant must be at least 18 years of age, at the time of signing the ICF.
Participants must have histological or cytological confirmation of advanced malignancy considered to be suitable for study treatment.
Eastern cooperative oncology group performance status 0-1.
Life expectancy greater than 12 weeks.
Progressive cancer at the time of study entry.

Show all 15Show fewer

Pharmacodynamics expansion cohorts: Participants must have at least 1 tumour suitable for biopsy and consent to having biopsies collected.
Negative pregnancy test (urine or serum) prior to start of dosing for women of childbearing potential.
Female participants must be post-menopausal, surgically sterile, or using an acceptable method of contraception for the duration of the study (from the time they sign consent) and for 12 weeks after the last dose of study treatment to prevent pregnancy.
For the duration of the study (from the time they sign consent) and for 12 weeks after the last dose of study treatment, sexually active male participants must be willing to use contraception.
Post-menopausal is defined as:
No menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the post-menopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy). However in the absence of 12 months of amenorrhea, a FSH measurement is insufficient.
Radiation-induced oophorectomy with last menses greater than 12 months ago.
Chemotherapy-induced menopause with greater than 12 month interval since last menses.
Surgical sterilisation.

Who cannot join

Any unresolved toxicities from prior therapy common terminology criteria for adverse event (CTCAE) Grade ≥2 (with the exception of alopecia).
Spinal cord compression or brain metastases unless definitively treated, asymptomatic, stable and not requiring steroids for at least 4 weeks.
As judged by the Investigator, any evidence of severe or uncontrolled medical conditions including but not limited to:
Uncontrolled diabetes mellitus, uncontrolled seizures, active infection requiring systemic antibiotics, antifungal or antiviral drugs, severe chronic obstructive pulmonary disease, severe Parkinson's disease, active inflammatory bowel disease, psychiatric condition, active bleeding diatheses, renal transplant, or active infection including any participant with active hepatitis B, hepatitis C or human immunodeficiency virus.
Any other malignancy which has been active or treated within the past 3 years, with the exception of in situ cancer of the cervix, non-melanoma skin cancer, ductal carcinoma in situ, Stage 1 Grade 1 endometrial carcinoma, or other solid tumours including lymphomas curatively treated with no evidence of disease for ≥5 years.
Refractory nausea and vomiting or unable to swallow and retain oral medication, chronic gastrointestinal diseases or previous bowel resection with clinically significant sequelae that would preclude adequate absorption of AZD7648, gastrointestinal symptoms CTCAE Grade >1, history of gastrointestinal ulceration and gastrointestinal haemorrhage within 6 months of first study drug administration.

Show all 14Show fewer

6 Receiving or having received anti-cancer treatment within the following periods prior to the first dose of investigational product:
Cytotoxic treatment: 3 weeks, (b) Non-cytotoxic drugs: including small molecule investigational products: 3 weeks or 5 half-lives (whichever is longest), (c) Biological products including investigational immuno-oncology agents: 4 weeks, (d) Radiation with a limited field for palliation: 1 week (3 months for radiation to the abdomen or pelvis), (e) Radiation to >30% of the bone marrow or with a wide field: 4 weeks, (f) Lung radiation: 60 days, (g) Major surgery: 4 weeks; minor surgery or biopsy: 1 week 7. During the 4 weeks prior to the first dose, receiving corticosteroids at a dose of >10 mg prednisone/day or equivalent for any reason. Ongoing low dose steroids for longer than 3 months (excluding inhalational, nasal, creams, lotions, and gels) are not allowed.
8. Receiving or having received concomitant medications, herbal supplements and/or foods known to significantly modulate CYP3A4 activity.
9. Prior exposure to a deoxyribonucleic acid-pharmacokinetics inhibitor or hypersensitivity to any excipient of the product.
10. Cardiac dysfunction as defined by any of the following within 6 months of study entry:
Acute myocardial infarction, (b) New York Heart Association Class II/III/IV heart failure, (c) Unstable angina, (d) Unstable cardiac arrhythmias 11. Any of the following cardiac criteria:
Known reduced left ventricular ejection fraction below the institutional lower limit of normal, (b) Mean resting corrected QT interval (QTc) >470 milliseconds obtained from 3 electrocardiograms in 24 hours using the Fridericia formula, (c) Any factors that increase the risk of QTc prolongation or arrhythmic events such as hypokalaemia, congenital long QT syndrome, immediate family history of long QT syndrome or unexplained sudden death under 40 years of age 12. Inadequate hematological or organ function 13. Involvement in the planning and/or conduct of the study. 14. Judgement by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements.
15. Previous enrolment in the present study. 16. For female participant only: currently pregnant or breast-feeding. 17. For food effect cohort only: insulin dependent diabetes. 18. History and/or presence of coronavirus disease 2019.

Trial locations and contacts

5 sites in 2 countries.

Country

City, postcode or hospital

5 sites in 2 countries

United Kingdom3 sites

Research Site
London, EC1A 7BE
Research Site
London, SE1 9RT
Research Site
Newcastle upon Tyne, NE7 7DN

Other trials in United Kingdom

United States2 sites

Research Site
Houston, Texas, 77030
Research Site
New Haven, Connecticut, 06510

Other trials in United States

About this study

Official title: A Phase I/IIa, Open-Label Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Ascending Doses of AZD7648 Monotherapy or in Combination With Either Cytotoxic Chemotherapies or Novel Anti-Cancer Agents in Patients With Advanced Malignancies

Read the detailed description

The modular design allows for an escalation of the dose of AZD7648 alone or in combination with either cytotoxic chemotherapies or novel anti-cancer agents, with intensive safety monitoring to ensure the safety of the participants.

The study consists of 2 modules each evaluating the safety and tolerability of AZD7648 monotherapy or with a specific combination partner.

Core module of the study is dose escalation (Part A) of AZD7648 monotherapy, administered orally, in participants with advanced solid tumours.

Combination module 1 has 2 study parts: Part A consisting of dose escalation cohorts and Part B, a safety and proof of concept Phase IIa expansion. A Safety Review Committee will review evaluable participants at each cohort and assess if the study should progress to Part B.

Conditions: Advanced Malignancies
Being tested: AZD7648, PLD
Keywords: Safety,, Pharmacokinetics,, Pegylated liposomal doxorubicin,, Dose finding

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AZD7648Drug
Core: AZD7648 will be administered orally
PLDDrug
Also called DOXIL, Caelyx
The starting dose of PLD is 40 mg/m^2, administered by intravenous infusion once every 4 weeks, for a maximum of 6 cycles

Study groups in NCT03907969
Study group	Role	What they receive
Core Module: AZD7648 Monotherapy	Experimental	AZD7648 will be administered orally on an empty stomach Receives: Drug: AZD7648
Combination Module 1: AZD7648 + PLD	Experimental	AZD7648 will be administered in combination with Pegylated liposomal doxorubicin (PLD) Receives: Drug: AZD7648; Drug: PLD

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Patients With Adverse Events or Serious Adverse Events
Safety and tolerability of AZD7648 when given orally to patients with advanced malignancies, as monotherapy and in combination with anti-cancer agents was assessed.
Measured: From Screening (Day -28) till study drug discontinuation (3.2 years)
Number of Patients With Dose Limiting Toxicities (DLTs)
A DLT is defined as an AE that occurs from the first dose of study treatment up to and including Cycle 1, Day 28 (the DLT assessment period) that is assessed as unrelated to the disease, intercurrent illness, or concomitant medications.
Measured: From Screening (Day -28) till study drug discontinuation (3.2 years)

Secondary outcomes (12)

Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf)
The AUCinf of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents.
Measured: Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose [each cycle is 28 days]
Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast)
The AUClast of AZD7648, following a single dose, when given orally as monotherapy and in combination with anti-cancer agents.
Measured: Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose (each cycle is 28 days)
Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ)
The AUCτ of AZD7648, at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents.
Measured: Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose (each cycle is 28 days)
Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax)
The Cmax of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents.
Measured: Monotherapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose, Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 0 Day 1 Pre-dose to 12 hours post dose and Cycle 1 Days 7, 8 Pre-dose to 8 hours post dose (each cycle is 28 days)
Time to Reach Maximum Plasma Concentration (Tmax)
The tmax of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents.
Measured: Monotherapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose, Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 0 Day 1 Pre-dose to 12 hours post dose and Cycle 1 Days 7, 8 Pre-dose to 8 hours post dose (each cycle is 28 days)
Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz)
The t½λ of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents.
Measured: Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose (each cycle is 28 days)
Accumulation Ratio for Area Under Curve (Rac AUC)
The Rac AUC of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents. Accumulation ratio for AUC, calculated by multiple dose AUCτ/single dose AUC(0-12) or AUC(0-24).
Measured: Monotherapy: Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 1 Days 7 and 8 Pre-dose to 8 hours post dose (each cycle is 28 days)
Accumulation Ratio for Cmax (Rac Cmax)
The Rac Cmax of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents. Accumulation ratio for Cmax, calculated by multiple dose Cmax/single dose Cmax.
Measured: Monotherapy: Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 1 Days 7 and 8 Pre-dose to 8 hours post dose (each cycle is 28 days)
Dose Proportionality (TCP)
The TCP of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents. Temporal change parameter in systemic exposure, calculated as multiple dose AUCtau/single dose AUCinf.
Measured: Monotherapy: Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 1 Days 7 and 8 Pre-dose to 8 hours post dose (each cycle is 28 days)
Objective Response Rate (ORR)
ORR is defined as the percentage of patients who have a confirmed visit response of complete response (CR) or partial response (PR) prior to any evidence of progression (as defined by Response Evaluation Criteria in Solid Tumours 1.1). CR is defined when all target lesions (TLs) and non-target lesions (NTLs) present at baseline have disappeared (with the exception of lymph nodes which must be <10mm to be considered non pathological) and no new lesions have developed since baseline. PR is defined when the sum of diameters of the TLs has decreased by 30% or more compared to baseline (with no evidence of progression) and the NTLs are at least stable with no evidence of new lesions.
Measured: First dose of study treatment on Cycle 1 Day 1 (each cycle is 28 days) until progression or the last evaluable assessment in the absence of progression (3.2 years)
Progression Free Survival (PFS) for Monotherapy
PFS is defined as the time from first dose of Cycle 1 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from study therapy or receives another anti-cancer therapy prior to progression. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as increased by > 20% or more compared to the smallest sum of diameters on study.
Measured: At 12 months
Progression Free Survival (PFS) for Combination Therapy
PFS is defined as the time from first dose of Cycle 1 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from study therapy or receives another anti-cancer therapy prior to progression. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as increased by > 20% or more compared to the smallest sum of diameters on study.
Measured: At 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Oct 20197 Dec 2022

First posted9 Apr 2019
Study start9 Oct 2019
Primary completion7 Dec 2022
Study completion7 Dec 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Advanced MalignanciesStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03907969
Sponsor's protocol ID: D9170C00001
Other IDs: 2018-003688-73, 2018
Status last verified: Jan 2024
First submitted: 21 Feb 2019
Last updated: 6 Feb 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. 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.

Publications

Goldberg FW, Finlay MRV, Ting AKT, Beattie D, Lamont GM, Fallan C, Wrigley GL, Schimpl M, Howard MR, Williamson B, Vazquez-Chantada M, Barratt DG, Davies BR, Cadogan EB, Ramos-Montoya A, Dean E. The Discovery of 7-Methyl-2-[(7-methyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino]-9-(tetrahydro-2H-pyran-4-yl)-7,9-dihydro-8H-purin-8-one (AZD7648), a Potent and Selective DNA-Dependent Protein Kinase (DNA-PK) Inhibitor. J Med Chem. 2020 Apr 9;63(7):3461-3471. doi: 10.1021/acs.jmedchem.9b01684. Epub 2020 Jan 15.
PubMed 31851518

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms

All Advanced Malignancies trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/IIa, Open-Label Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Ascending Doses of AZD7648 Monotherapy or in Combination With Either Cytotoxic Chemotherapies or Novel Anti-Cancer Agents in Patients With Advanced Malignancies
ClinicalTrials.gov ID: NCT03907969
Acronym / sponsor ID: D9170C00001
Conditions: Advanced Malignancies
Keywords: Safety,, Pharmacokinetics,, Pegylated liposomal doxorubicin,, Dose finding
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 30 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Parexel
Study start: 9 Oct 2019 (actual)
Primary completion: 7 Dec 2022 (actual)
Study completion: 7 Dec 2022 (actual)
First posted: 9 Apr 2019 (actual)
Results: Posted 6 Feb 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

The study consists of 2 modules each evaluating the safety and tolerability of AZD7648 monotherapy or with a specific combination partner.

Core module of the study is dose escalation (Part A) of AZD7648 monotherapy, administered orally, in participants with advanced solid tumours.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Core Module: AZD7648 Monotherapy	Experimental	Drug: AZD7648AZD7648 will be administered orally on an empty stomach
Combination Module 1: AZD7648 + PLD	Experimental	Drug: AZD7648, Drug: PLDAZD7648 will be administered in combination with Pegylated liposomal doxorubicin (PLD)

Who may qualify

Ages: 18 to 130 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (15 listed)

Capable and willing to give signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF).
Participant must be at least 18 years of age, at the time of signing the ICF.
Participants must have histological or cytological confirmation of advanced malignancy considered to be suitable for study treatment.
Eastern cooperative oncology group performance status 0-1.
Life expectancy greater than 12 weeks.

Key exclusion criteria (14 listed)

Any unresolved toxicities from prior therapy common terminology criteria for adverse event (CTCAE) Grade ≥2 (with the exception of alopecia).
Spinal cord compression or brain metastases unless definitively treated, asymptomatic, stable and not requiring steroids for at least 4 weeks.
As judged by the Investigator, any evidence of severe or uncontrolled medical conditions including but not limited to:
Any other malignancy which has been active or treated within the past 3 years, with the exception of in situ cancer of the cervix, non-melanoma skin cancer, ductal carcinoma in situ, Stage 1 Grade 1 endometrial carcinoma, or other solid tumours including lymphomas curatively treated with no evidence of disease for ≥5 years.
Refractory nausea and vomiting or unable to swallow and retain oral medication, chronic gastrointestinal diseases or previous bowel resection with clinically significant sequelae that would preclude adequate absorption of AZD7648, gastrointestinal symptoms CTCAE Grade >1, history of gastrointestinal ulceration and gastrointestinal haemorrhage within 6 months of first study drug administration.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AZD7648Core: AZD7648 will be administered orally	Drug	Combination Module 1: AZD7648 + PLD, Core Module: AZD7648 Monotherapy
PLDAlso: DOXIL, CaelyxThe starting dose of PLD is 40 mg/m^2, administered by intravenous infusion once every 4 weeks, for a maximum of 6 cycles	Drug	Combination Module 1: AZD7648 + PLD

Primary outcome

Number of Patients With Adverse Events or Serious Adverse Events
Time frame: From Screening (Day -28) till study drug discontinuation (3.2 years)
Safety and tolerability of AZD7648 when given orally to patients with advanced malignancies, as monotherapy and in combination with anti-cancer agents was assessed.
Number of Patients With Dose Limiting Toxicities (DLTs)
Time frame: From Screening (Day -28) till study drug discontinuation (3.2 years)
A DLT is defined as an AE that occurs from the first dose of study treatment up to and including Cycle 1, Day 28 (the DLT assessment period) that is assessed as unrelated to the disease, intercurrent illness, or concomitant medications.

12 secondary outcomes

Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf)
Time frame: Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose [each cycle is 28 days]
Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast)
Time frame: Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose (each cycle is 28 days)
Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ)
Time frame: Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose (each cycle is 28 days)
Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax)
Time frame: Monotherapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose, Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 0 Day 1 Pre-dose to 12 hours post dose and Cycle 1 Days 7, 8 Pre-dose to 8 hours post dose (each cycle is 28 days)
Time to Reach Maximum Plasma Concentration (Tmax)
Time frame: Monotherapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose, Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 0 Day 1 Pre-dose to 12 hours post dose and Cycle 1 Days 7, 8 Pre-dose to 8 hours post dose (each cycle is 28 days)
Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz)
Time frame: Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose (each cycle is 28 days)
Accumulation Ratio for Area Under Curve (Rac AUC)
Time frame: Monotherapy: Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 1 Days 7 and 8 Pre-dose to 8 hours post dose (each cycle is 28 days)
Accumulation Ratio for Cmax (Rac Cmax)
Time frame: Monotherapy: Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 1 Days 7 and 8 Pre-dose to 8 hours post dose (each cycle is 28 days)
Dose Proportionality (TCP)
Time frame: Monotherapy: Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 1 Days 7 and 8 Pre-dose to 8 hours post dose (each cycle is 28 days)
Objective Response Rate (ORR)
Time frame: First dose of study treatment on Cycle 1 Day 1 (each cycle is 28 days) until progression or the last evaluable assessment in the absence of progression (3.2 years)
Progression Free Survival (PFS) for Monotherapy
Time frame: At 12 months
Progression Free Survival (PFS) for Combination Therapy
Time frame: At 18 months

Results and safety

Results posted to the registry on 6 Feb 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1: AZD7648 Dose A (Monotherapy)	1	1
Cohort 2: AZD7648 Dose A1 (Monotherapy)	1	0
Cohort 3: AZD7648 Dose B1 (Monotherapy)	1	0
Cohort 4: AZD7648 Dose C1 (Monotherapy)	1	0
Cohort 5: AZD7648 Dose D1 (Monotherapy)	3	2
Cohort 6: AZD7648 Dose E1 (Monotherapy)	4	1
Cohort 7: AZD7648 Dose F1 (Monotherapy)	3	1
Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy)	0	0
Cohort 1: AZD7648 Dose C + PLD (Combination Therapy)	0	0
Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy)	0	0
Cohort 3: AZD7648 Dose X + PLD (Combination Therapy)	0	0

Primary outcome: Number of Patients With Adverse Events or Serious Adverse Events

Time frame: From Screening (Day -28) till study drug discontinuation (3.2 years). Count of participants. Unit: Participants

Measure	Cohort 1: AZD7648 Dose A (Monotherapy) n = 1	Cohort 2: AZD7648 Dose A1 (Monotherapy) n = 1	Cohort 3: AZD7648 Dose B1 (Monotherapy) n = 1	Cohort 4: AZD7648 Dose C1 (Monotherapy) n = 1	Cohort 5: AZD7648 Dose D1 (Monotherapy) n = 3	Cohort 6: AZD7648 Dose E1 (Monotherapy) n = 4	Cohort 7: AZD7648 Dose F1 (Monotherapy) n = 3	Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) n = 2	Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) n = 2	Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) n = 5	Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) n = 7
Any AE	0	1	1	1	2	4	3	2	2	4	7
Any AE possibly related to AZD7648	0	0	0	0	1	2	2	2	2	4	7
Any AE possibly related to PLD	–	–	–	–	–	–	–	2	2	4	4
Any AE of CTCAE Grade 3 or higher	0	0	0	0	2	4	2	2	2	0	5
Any AE of CTCAE Grade 3 or higher, possibly related to AZD7648	0	0	0	0	0	2	2	2	2	0	4
Any AE of CTCAE Grade 3 or higher, possibly related to PLD	–	–	–	–	–	–	–	2	2	0	1
Any AE with outcome of death	0	0	0	0	0	1	0	0	0	0	1
Any AE with outcome of death, possibly related to AZD7648	0	0	0	0	0	0	0	0	0	0	0

Population analysed: All patients who received at least 1 dose of any study treatment.

Primary outcome: Number of Patients With Dose Limiting Toxicities (DLTs)

Time frame: From Screening (Day -28) till study drug discontinuation (3.2 years). Count of participants. Unit: Participants

Measure	Cohort 1: AZD7648 Dose A (Monotherapy) n = 1	Cohort 2: AZD7648 Dose A1 (Monotherapy) n = 1	Cohort 3: AZD7648 Dose B1 (Monotherapy) n = 1	Cohort 4: AZD7648 Dose C1 (Monotherapy) n = 1	Cohort 5: AZD7648 Dose D1 (Monotherapy) n = 3	Cohort 6: AZD7648 Dose E1 (Monotherapy) n = 4	Cohort 7: AZD7648 Dose F1 (Monotherapy) n = 3	Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) n = 2	Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) n = 2	Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) n = 4	Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) n = 7
Value	0	0	0	0	0	0	1	2	0	0	1

Population analysed: All patients who received at least 1 dose of any study treatment.

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: From Screening (Day -28) till study drug discontinuation (3.2 years). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1: AZD7648 Dose A (Monotherapy)	0 of 1 (0%)	0 of 1 (0%)	0 of 1
Cohort 2: AZD7648 Dose A1 (Monotherapy)	0 of 1 (0%)	1 of 1 (100%)	0 of 1
Cohort 3: AZD7648 Dose B1 (Monotherapy)	0 of 1 (0%)	1 of 1 (100%)	1 of 1
Cohort 4: AZD7648 Dose C1 (Monotherapy)	0 of 1 (0%)	1 of 1 (100%)	1 of 1
Cohort 5: AZD7648 Dose D1 (Monotherapy)	1 of 3 (33.3%)	2 of 3 (66.7%)	1 of 3
Cohort 6: AZD7648 Dose E1 (Monotherapy)	4 of 4 (100%)	4 of 4 (100%)	1 of 4
Cohort 7: AZD7648 Dose F1 (Monotherapy)	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy)	1 of 2 (50%)	2 of 2 (100%)	0 of 2
Cohort 1: AZD7648 Dose C + PLD (Combination Therapy)	1 of 2 (50%)	2 of 2 (100%)	1 of 2
Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy)	0 of 5 (0%)	4 of 5 (80%)	0 of 5
Cohort 3: AZD7648 Dose X + PLD (Combination Therapy)	4 of 7 (57.1%)	7 of 7 (100%)	1 of 7

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31851518Goldberg FW, Finlay MRV, Ting AKT, Beattie D, Lamont GM, Fallan C, Wrigley GL, Schimpl M, Howard MR, Williamson B, Vazquez-Chantada M, Barratt DG, Davies BR, Cadogan EB, Ramos-Montoya A, Dean E. The Discovery of 7-Methyl-2-[(7-methyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino]-9-(tetrahydro-2H-pyran-4-yl)-7,9-dihydro-8H-purin-8-one (AZD7648), a Potent and Selective DNA-Dependent Protein Kinase (DNA-PK) Inhibitor. J Med Chem. 2020 Apr 9;63(7):3461-3471. doi: 10.1021/acs.jmedchem.9b01684. Epub 2020 Jan 15.
Protocol redactedLink provided by the sponsor.
SAP redactedLink provided by the sponsor.
CSR Synopsis redactedLink provided by the sponsor.
Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. 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.

Related trials for Advanced Malignancies

Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Dr Timothy Yap principal investigator

MD Anderson Cancer Center, 1400 Holcombe Blvd. Houston, Texas, 77030

5 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AZD7648 and PLD in people with Advanced Malignancies, run by AstraZeneca at 5 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United Kingdom, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients With Adverse Events or Serious Adverse Events (time frame: From Screening (Day -28) till study drug discontinuation (3.2 years)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03907969, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2024.