B-cell MalignanciesPhase 1/2TITANiumNCT06542250
A Study to Evaluate Safety, PK, PD and Efficacy of AZD5492, a T Cell-engaging Antibody Targeting CD20 in Subjects With R/R B-Cell Malignancies.
A Phase 1/2 study testing AZD5492 in people with B-cell Malignancies, run by AstraZeneca at 31 sites in 10 countries.
Trial summary
This is a Phase I/II study designed to evaluate if experimental T cell engaging antibody targeting CD20 AZD5492 is safe, tolerable and efficacious in participants with Relapsed or Refractory B-Cell Malignancies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- B-cell Malignancies
- What is being tested?
- AZD5492
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 174 participants
- Where
- 31 sitesin 10 countries
- Study dates
- 18 Sep 2024to 18 Dec 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥18 years of age;
- Histologically documented CD20+ mature B-cell neoplasm
- Large B-cell lymphoma
- Follicular lymphoma
- Mantle cell lymphoma
- Chronic lymphocytic leukemia
Show all 10Show fewer
- Small lymphocytic lymphoma
- Relapsed, progressive and/or refractory disease following at least 2 prior lines of therapy;
- ECOG performance status of ≤ 2 (< 2 in EU countries).
- The above is a summary, other inclusion criteria details may apply.
Who cannot join
- Any neoplasm histology not specified in the IC section;
- Active CNS involvement in lymphoma;
- CNS pathology including but not limited to any history of seizure disorder/epilepsy;
- Prior allogeneic HSCT within 180 days, prior autologous HSCT within 90 days, or cell therapy within 90 days of start of therapy;
- History of Grade ≥ 3 CRS or Grade ≥ 3 ICANS;
- Active and uncontrolled infections;
- Unresolved AEs ≥2 Grade due to prior anticancer therapies, with some exceptions
- The above is a summary, other exclusion criteria details may apply.
Trial locations and contacts
31 sites in 10 countries. Contact the study team or a site near you to ask about taking part.
AstraZeneca Clinical Study Information Center contact
31 sites in 10 countries
United States10 sites, 9 recruiting
- Withdrawn
Research Site
Boston, Massachusetts, 02215
- Recruiting
Research Site
Charlotte, North Carolina, 28203
- Recruiting
Research Site
Hackensack, New Jersey, 07601
- Recruiting
Research Site
Houston, Texas, 77030
- Recruiting
Research Site
La Jolla, California, 92093
- Recruiting
Research Site
New York, New York, 10021
- Recruiting
Research Site
New York, New York, 10029
- Recruiting
Research Site
Rochester, Minnesota, 55905
- Recruiting
Research Site
Seattle, Washington, 98109
- Recruiting
Research Site
Winston-Salem, North Carolina, 27157
Germany4 sites, 4 recruiting
- Recruiting
Research Site
Göttingen, DE-37099
- Recruiting
Research Site
München, 81675
- Recruiting
Research Site
Ulm, 89081
- Recruiting
Research Site
Würzburg, 97080
Canada3 sites, 3 recruiting
- Recruiting
Research Site
Calgary, Alberta, T2N 5G2
- Recruiting
Research Site
Montreal, Quebec, H3T 1R2
- Recruiting
Research Site
Toronto, Ontario, M5G 2M9
Spain3 sites, 3 recruiting
- Recruiting
Research Site
Barcelona, 08035
- Recruiting
Research Site
L'Hospitalet de Llobregat, 08908
- Recruiting
Research Site
Madrid, 28040
Australia2 sites, 2 recruiting
- Recruiting
Research Site
Melbourne, 3000
- Recruiting
Research Site
Nedlands, 6009
China2 sites, 2 recruiting
- Recruiting
Research Site
Hangzhou, 310003
- Recruiting
Research Site
Shanghai, 200025
France2 sites, 2 recruiting
- Recruiting
Research Site
Pessac, 33604
- Recruiting
Research Site
Villejuif, 94805
Italy2 sites, 2 recruiting
- Recruiting
Research Site
Bologna, 40138
- Recruiting
Research Site
Milan, 20133
Japan2 sites, 2 recruiting
- Recruiting
Research Site
Chūōku, 104-0045
- Recruiting
Research Site
Kashiwa, 277-8577
About this study
Official title: A Modular Phase I/II Open-label Dose Escalation and Dose Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of AZD5492, a T Cell-engaging Antibody Targeting CD20 in Subjects With Relapsed or Refractory B-Cell Malignancies (TITANium)
This is a Phase I/II study designed to evaluate if experimental T cell engaging antibody targeting CD20 AZD5492 is safe, tolerable and efficacious in participants with Relapsed or Refractory B-Cell Malignancies.
- Conditions
- B-cell Malignancies
- Being tested
- AZD5492
- Keywords
- CD20, CD8, T cell engager, TCR, AZD5492, Relapsed, Refractory, B-cell malignancies, CLL, Chronic lymphocytic leukemia, SLL, Small lymphocytic lymphoma, MCL, Mantle cell lymphoma, LBCL, Large B-cell lymphoma, FL, Follicular lymphoma, TITANium, TCE
- Medical subject headings
- Recurrence, Leukemia, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Mantle-Cell, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD5492Drug
CD8/TCR based T-cell engaging antibody targeting CD20, which is administered subcutaneously
| Study group | Role | What they receive |
|---|---|---|
| Module 1: AZD5492 Monotherapy | Experimental | AZD5492 monotherapy for Relapsed or Refractory B-Cell Malignancies. Receives: Drug: AZD5492 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of dose limiting toxicities (DLTs).
DLTs are dose-limiting toxicities as defined in the study protocol.
Measured: Module 1 - From the first administration of AZD5492 until the end of cycle 1 (up to 5 weeks).
Safety evaluation of AZD5492: Number of participants with treatment-related adverse events.
Incidence and severity of AEs, AESIs, and SAEs
Measured: Module 1 - From the first administration of AZD5492 within the duration of the treatment period, up to and including 90 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy.
Tolerability evaluation of AZD5492: Number of participants with treatment-related adverse events.
SAEs/AEs leading to discontinuation of AZD5492.
Measured: Module 1 - From the first administration of AZD5492 within the duration of the treatment period, up to and including 90 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy.
Secondary outcomes (12)
Overall Response Rate (ORR)
The proportion of participants with a complete response or partial response, according to Lugano criteria for malignant lymphoma and iwCLL 2018 criteria for CLL.
Measured: Module 1 - From first dose of AZD5492 up to 2 years after last dose.
Complete Response Rate (CR Rate)
The proportion of participants with a complete response (CR), according to Lugano criteria for malignant lymphoma and iwCLL 2018 criteria for CLL.
Measured: Module 1 - From first dose of AZD5492 up to 2 years after last dose.
Duration of Response (DoR)
The time from the date of first documented response until the date of documented progression (according to Lugano criteria for malignant lymphoma and iwCLL 2018 criteria for CLL) or death due to any cause.
Measured: Module 1 - From first dose of AZD5492 up to 2 years after last dose.
Progression-free Survival (PFS)
The time from the date of first dose until the date of documented disease progression (according to Lugano criteria for malignant lymphoma and iwCLL 2018 criteria for CLL) or death due to any cause.
Measured: Module 1 - From first dose of AZD5492 up to 2 years after last dose.
Overall Survival (OS)
The time from the date of first dose until date of death due to any cause.
Measured: Module 1 - From first dose of AZD5492 up to 2 years after last dose.
Pharmacokinetics of AZD5492: serum concentration of study drug
Maximum observed serum concentration of AZD5492.
Measured: Module 1 - From informed consent until 90 days after last dose of AZD5492.
Pharmacokinetics of AZD5492: Maximum plasma concentration of the study drug (Cmax).
Maximum observed plasma concentration of AZD5492.
Measured: Module 1 - From informed consent until 90 days after last dose of AZD5492.
Pharmacokinetics of AZD5492: Area under the concentration time curve (AUC).
Area under the plasma concentration-time curve.
Measured: Module 1 - From informed consent until 90 days after last dose of AZD5492.
Pharmacokinetics of AZD5492: apparent clearance
The volume of plasma from which the study drug is completely removed per unit time.
Measured: Module 1 - From informed consent until 90 days after last dose of AZD5492.
Pharmacokinetics of AZD5492: Half-life (t 1/2)
Terminal elimination half-life.
Measured: Module 1 - From informed consent until 90 days after last dose of AZD5492.
To determine the immunogenicity of AZD5492
The number of participants who develop ADAs measured in serum.
Measured: Module 1 - From informed consent until 90 days after last dose of AZD5492.
To determine the immunogenicity of AZD5492
The percentage of participants who develop ADAs measured in serum.
Measured: Module 1 - From informed consent until 90 days after last dose of AZD5492.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2024
- Study start18 Sep 2024
- Primary completion18 Dec 2029 (estimated)
- Study completion18 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B-cell 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
- Not applicable
- Intervention model
- Sequential
- Model description
- The study consists of individual modules each evaluating the safety, tolerability, PK, immunogenicity, pharmacodynamics, and preliminary efficacy of AZD5492 as monotherapy or in combination with other anticancer treatments in participants with R/R B-cell malignancies. \- Module 1: AZD5492 Monotherapy
- Masking
- None (open label)
- Enrolment
- 174 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06542250
- Sponsor's protocol ID
- D9960C00001
- Acronym
- TITANium
- Status last verified
- Sep 2026
- First submitted
- 29 Jul 2024
- Last updated
- 30 Sep 2026
- Results posted
- 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 Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://www.astrazenecaclinicaltrials.com/our-transparency-commitments/. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Modular Phase I/II Open-label Dose Escalation and Dose Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of AZD5492, a T Cell-engaging Antibody Targeting CD20 in Subjects With Relapsed or Refractory B-Cell Malignancies (TITANium)
- ClinicalTrials.gov ID
- NCT06542250
- Acronym / sponsor ID
- TITANium / D9960C00001
- Conditions
- B-cell Malignancies
- Keywords
- CD20, CD8, T cell engager, TCR, AZD5492, Relapsed, Refractory, B-cell malignancies, CLL, Chronic lymphocytic leukemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 174 participants (estimated)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 18 Sep 2024 (actual)
- Primary completion
- 18 Dec 2029 (estimated)
- Study completion
- 18 Dec 2029 (estimated)
- First posted
- 7 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase I/II study designed to evaluate if experimental T cell engaging antibody targeting CD20 AZD5492 is safe, tolerable and efficacious in participants with Relapsed or Refractory B-Cell Malignancies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The study consists of individual modules each evaluating the safety, tolerability, PK, immunogenicity, pharmacodynamics, and preliminary efficacy of AZD5492 as monotherapy or in combination with other anticancer treatments in participants with R/R B-cell malignancies. - Module 1: AZD5492 Monotherapy
| Arm | Type | Receives |
|---|---|---|
| Module 1: AZD5492 Monotherapy | Experimental | Drug: AZD5492AZD5492 monotherapy for Relapsed or Refractory B-Cell Malignancies. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- ≥18 years of age;
- Histologically documented CD20+ mature B-cell neoplasm
- Relapsed, progressive and/or refractory disease following at least 2 prior lines of therapy;
- ECOG performance status of ≤ 2 (< 2 in EU countries).
- The above is a summary, other inclusion criteria details may apply.
Key exclusion criteria (8 listed)
- Any neoplasm histology not specified in the IC section;
- Active CNS involvement in lymphoma;
- CNS pathology including but not limited to any history of seizure disorder/epilepsy;
- Prior allogeneic HSCT within 180 days, prior autologous HSCT within 90 days, or cell therapy within 90 days of start of therapy;
- History of Grade ≥ 3 CRS or Grade ≥ 3 ICANS;
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 |
|---|---|---|
| AZD5492CD8/TCR based T-cell engaging antibody targeting CD20, which is administered subcutaneously | Drug | Module 1: AZD5492 Monotherapy |
Primary outcome
Frequency of dose limiting toxicities (DLTs).
Time frame: Module 1 - From the first administration of AZD5492 until the end of cycle 1 (up to 5 weeks).
DLTs are dose-limiting toxicities as defined in the study protocol.
Safety evaluation of AZD5492: Number of participants with treatment-related adverse events.
Time frame: Module 1 - From the first administration of AZD5492 within the duration of the treatment period, up to and including 90 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy.
Incidence and severity of AEs, AESIs, and SAEs
Tolerability evaluation of AZD5492: Number of participants with treatment-related adverse events.
Time frame: Module 1 - From the first administration of AZD5492 within the duration of the treatment period, up to and including 90 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy.
SAEs/AEs leading to discontinuation of AZD5492.
12 secondary outcomes
Overall Response Rate (ORR)
Time frame: Module 1 - From first dose of AZD5492 up to 2 years after last dose.
Complete Response Rate (CR Rate)
Time frame: Module 1 - From first dose of AZD5492 up to 2 years after last dose.
Duration of Response (DoR)
Time frame: Module 1 - From first dose of AZD5492 up to 2 years after last dose.
Progression-free Survival (PFS)
Time frame: Module 1 - From first dose of AZD5492 up to 2 years after last dose.
Overall Survival (OS)
Time frame: Module 1 - From first dose of AZD5492 up to 2 years after last dose.
Pharmacokinetics of AZD5492: serum concentration of study drug
Time frame: Module 1 - From informed consent until 90 days after last dose of AZD5492.
Pharmacokinetics of AZD5492: Maximum plasma concentration of the study drug (Cmax).
Time frame: Module 1 - From informed consent until 90 days after last dose of AZD5492.
Pharmacokinetics of AZD5492: Area under the concentration time curve (AUC).
Time frame: Module 1 - From informed consent until 90 days after last dose of AZD5492.
Pharmacokinetics of AZD5492: apparent clearance
Time frame: Module 1 - From informed consent until 90 days after last dose of AZD5492.
Pharmacokinetics of AZD5492: Half-life (t 1/2)
Time frame: Module 1 - From informed consent until 90 days after last dose of AZD5492.
To determine the immunogenicity of AZD5492
Time frame: Module 1 - From informed consent until 90 days after last dose of AZD5492.
To determine the immunogenicity of AZD5492
Time frame: Module 1 - From informed consent until 90 days after last dose of AZD5492.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2026.
- TYC AustraliaLink provided by the sponsor.
- TYC Canada EN versionLink provided by the sponsor.
- TYC Canada FRLink provided by the sponsor.
- TYC ChinaLink provided by the sponsor.
- TYC DenmarkLink provided by the sponsor.
- TYC GermanyLink 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 Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://www.astrazenecaclinicaltrials.com/our-transparency-commitments/. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
Related trials for B-cell Malignancies
RecruitingPhase 2/3
A Clinical Trial of MK-1045 in People With B-cell Acute Lymphoblastic Leukemia (MK-1045-005)
B-cell Acute Lymphoblastic Leukemia
Active, not recruitingPhase 1/2
Tafasitamab, Retifanlimab, and Rituximab in Combination With Standard Therapy for the Treatment of Diffuse Large B-cell Lymphoma
Diffuse Large B-Cell Lymphoma, Grade 3b Follicular Lymphoma
RecruitingPhase 2
Sonrotoclax, Rituximab, and Zanubrutinib in Treating Participants With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Mantle Cell Lymphoma
Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma
Not yet recruitingPhase 1
4SCAR19U T Cells Targeting B Cell Malignancies
B Cell Malignancies
RecruitingPhase 2
Testing the Combination of Venetoclax and Rituximab, in Comparison to the Usual Treatment (Ibrutinib Plus Rituximab or Zanubrutinib Alone) for Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma
Lymphoplasmacytic Lymphoma, Waldenstrom Macroglobulinemia
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.
AstraZeneca Clinical Study Information Center contact
31 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AZD5492 in people with B-cell Malignancies, run by AstraZeneca at 31 sites in 10 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 10 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 30 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 31 sites in United States, Germany, Canada, Spain, Australia and 5 more countries. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact AstraZeneca Clinical Study Information Center (1-877-240-9479, information.center@astrazeneca.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of dose limiting toxicities (DLTs). (time frame: Module 1 - From the first administration of AZD5492 until the end of cycle 1 (up to 5 weeks).). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Sep 2026.