A Study of AZD0486 Monotherapy or in Combination With Other Anti-Cancer Agents for Mature B-Cell Malignancies
PHASE1PHASE2RECRUITING
The purpose of this study is to assess the safety and efficacy of AZD0486 administered as monotherapy or in combination with other anticancer agents in participants with hematological malignancies.
Study details:
This is open-label, multi-center study to evaluate the safety and preliminary efficacy of AZD0486 administered as monotherapy and in combination with other anticancer agents in participants with mature B-cell hematologic malignancies. This master study currently includes 3 substudies and each substudy focusing on a defined population:. Substudy 1: Relapsed/refractory (R/R) Chronic lymphocytic leukaemia (CLL)/ Small lymphocytic lymphoma (SLL) Substudy 2: R/R Mantle-cell lymphoma (MCL) Substudy 3: Large B-cell lymphoma (LBCL) or R/R B-cell non-Hodgkin lymphoma (B-NHL) (not applicable to US).
The study will have the following sequential periods:. 1. Screening period of 28 days.
2. Treatment period. 3.
Follow-up period.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Contraception use during treatment and at least 90 days after final dose.
- Confirmed CD19 expression if prior anti-CD19 therapy.
- Participants with CLL must require treatment according to the international workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria.
- SLL: at least 1 measurable site per Lugano.
- Absolute lymphocytes <10,000.
- Cohort 1A and 1C: at least 2 prior lines of systemic therapy for CLL/SLL.
- Cohort 1B: at least 1 prior line of therapy and is bruton tyrosine kinase inhibitor (BTKi)-sensitive.
- MCL diagnosis per WHO.
- Clinical Stage II, III, or IV by Ann Arbor Classification.
- At least 1 measurable site per Lugano.
- ALC < 10,000.
- Cohort 2A and 2C: Relapse or progressed after 2 or more lines of therapy including BTKi.
- Large B-cell lymphoma per WHO 2022.
- R/R B-NHL after at least 1 prior line of therapy.
- International Prognostic Index (IPI) 2-5.
- At least 1 measurable site as per Lugano.
- Left ventricular ejection fraction (LVEF) >50%.
- Contraception at least 90 days after last dose of AZD0486 or 4 months after last dose of vincristine, and 6 months after the last dose of cyclophosphamide, or doxorubicin.
Exclusion criteria
- Central nervous system (CNS) lymphoma.
- Surgery within 14 days of study drug.
- Clinically significant cardiovascular (CV) disease.
- Unresolved Grade >2 AEs from prior anticancer therapy (except alopecia or fatigue).
- Any anticancer therapy within 5 half-lives or 21 days (whichever is shorter) prior to treatment.
- Radiation therapy within 28 days.
- Prior CAR T-cell therapy or autologous-haematopoietic stem cell transplant (HSCT) within 12 weeks or prior T-cell engager (TCE) within 8 weeks.
- Prior Grade > 3 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) event.
- Prior allogeneic HSCT or solid organ transplantation within 24 weeks of starting Cycle 1 Day 1.
- CLL transformation to more aggressive lymphoma.
- Cohort 1B: bleeding diathesis, CYP3A inhibitor or inducer, history of ICH or stroke within 24 weeks, GI malabsorption, receiving vitamin K antagonist.
- Mediastinal grey-zone lymphoma, Burkitt, Richter's transformation, primary effusion large B-cell lymphoma (LBCL).
- Cumulative dose of anthracycline >150 mg/m2.
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE1PHASE2
Study ID
NCT06564038
Intervention or treatment
DRUG: AZD0486
DRUG: Prednisone (or equivalent)
DRUG: Rituximab
DRUG: Cyclophosphamide
DRUG: Vincristine
DRUG: Doxorubicin
DRUG: Acalabrutinib
Conditions
- Chronic Lymphocytic Leukaemia
- Small Lymphocytic Lymphoma
- Mantle-cell Lymphoma
- Large B-cell Lymphoma
- B-cell Non-Hodgkin Lymphoma
You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.
Research sites nearby
Closest Location:
Research Site
Select from list below to view details:
Research Site
Heidelberg, Australia
Research Site
Melbourne, Australia
Research Site
Nedlands, Australia
Loading map...
Who is running the clinical trial?
A
AstraZeneca
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Substudy 1 (RR CLL/SLL): Cohort 1A (Surovatamig Monotherapy)
| Drug: Surovatamig |
EXPERIMENTAL: Substudy 1 (RR CLL/SLL): Cohort 1B (Surovatamig + Acalabrutinib)
| Drug: Surovatamig, Drug: Acalabrutinib |
EXPERIMENTAL: Substudy 1 (RR CLL/SLL): Cohort 1C (Surovatamig Monotherapy)
| Drug: Surovatamig |
EXPERIMENTAL: Substudy 2 (RR MCL): Cohort 2A (Surovatamig Monotherapy)
| Drug: Surovatamig |
EXPERIMENTAL: Substudy 2 (RR MCL): Cohort 2C (Surovatamig Monotherapy)
| Drug: Surovatamig |
EXPERIMENTAL: Substudy 3 (LBCL): Cohort 3A 2SUD (Surovatamig + RCHOP)
| Drug: Surovatamig, Drug: Prednisone (or equivalent), Drug: Rituximab, Drug: Cyclophosphamide, Drug: Vincristine, Drug: Doxorubicin |
EXPERIMENTAL: Substudy 3 (LBCL): Cohort 3B 3SUD (Surovatamig + RCHOP)
| Drug: Surovatamig, Drug: Prednisone (or equivalent), Drug: Rituximab, Drug: Cyclophosphamide, Drug: Vincristine, Drug: Doxorubicin |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Adverse Events, Serious Adverse Events and Adverse Events of Special Interest | Safety and tolerability of AZD0486 as monotherapy and in combination with other anticancer agents across mature B-cell malignancies. | Up to 6 years 4 months |
| Number of Participants with Dose Limiting Toxicity (DLTs) | Safety and tolerability of AZD0486 as monotherapy and in combination with other anticancer agents across mature B-cell malignancies. | Up to 2 months |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) | ORR is defined as percentage of participants achieving either a partial response (PR) or complete response (CR) based on response criteria for International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 and Lugano 2014 assessed by investigator (substudy 1) and percentage of participants achieving CR as best response based on Lugano 2014 Response Criteria by investigator assessment (substudies 2 and 3). | Up to 6 years 4 months |
| Complete Response (CR) Rate | CR rate is defined as percentage of participants achieving CR as best response based on response criteria for iwCLL 2018 and Lugano 2014 assessed by investigator (substudy 1) and percentage of participants achieving CR as best response based on Lugano 2014 Response Criteria by investigator assessment (substudies 2 and 3). | Up to 6 years 4 months |
| Duration of Response (DoR) | DoR is defined as time from the date of first documented response until date of documented progression based on response criteria for iwCLL 2018 and Lugano 2014 assessed by investigator, relapse or death (substudy 1) and time from the date of first documented response until date of documented progression based on Lugano 2014 Response Criteria by investigator assessment, relapse or death (substudies 2 and 3). | Up to 6 years 4 months |
| Maximum Observed Concentration (Cmax) | The PK (Cmax) of AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated. | Up to 90 days after last dose |
| Area Under the Concentration-time Curve (AUC) | The PK (AUC) of AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated. | Up to 90 days after last dose |
| Minimum Observed Concentration (Cmin) | The PK (Cmin) of AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated. | Up to 90 days after last dose |
| Time to Reach Maximum Concentration (Tmax) | The PK (Tmax) of AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated. | Up to 90 days after last dose |
| Trough Plasma Concentration (Ctrough) | The PK (Ctrough) of AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated. | Up to 90 days after last dose |
| Half Life (t1/2) of AZD0486 | The PK (t1/2) of AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated. | Up to 90 days after last dose |
| Clearance (CL) of AZD0486 | The PK (CL) of AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated. | Up to 90 days after last dose |
| Number of Participants with Anti-drug Antibody (ADA) for AZD0486 | The incidence of immunogenicity of SC AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated. | Up to 90 days after last dose |
Are you running this trial?If you're a clinic or sponsor, you can claim this study.
References
Clinical Trials Gov: A Study of AZD0486 Monotherapy or in Combination With Other Anti-Cancer Agents for Mature B-Cell MalignanciesOther trials to consider
Loading suggested trials...
