AZD0486 for Lymphoma

(Soundtrack-E Trial)

Recruiting at 67 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: AstraZeneca

Must not be taking: CYP3A inhibitors, Vitamin K antagonists

Disqualifiers: CNS lymphoma, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

276 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AZD0486 to determine its safety and effectiveness for certain blood cancers. Participants will be divided into groups, with some receiving AZD0486 alone and others receiving it alongside other cancer-fighting drugs. Suitable candidates have specific types of lymphoma, such as chronic lymphocytic leukemia (CLL) or large B-cell lymphoma, and have not responded to prior treatments. The trial seeks individuals needing additional treatment options for these conditions. As a Phase 1 trial, participants will be among the first to receive AZD0486, aiding researchers in understanding how the treatment works in people.

Will I have to stop taking my current medications?

The trial requires that you stop any anticancer therapy at least 21 days before starting the study drug. If you are taking a CYP3A inhibitor or inducer, you may need to stop, especially for certain cohorts. The protocol does not specify other medications, so it's best to discuss with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that AZD0486 is generally safe for patients with blood cancers when used alone. Early results from past studies indicate it helps treat these conditions without causing serious side effects.

When combined with acalabrutinib, AZD0486 still appears safe. Acalabrutinib, when used with AZD0486, has been shown to slow the progression of some cancers.

For those considering AZD0486 with R-CHOP (a common chemotherapy treatment), studies suggest that this combination is usually well-tolerated.

Overall, AZD0486 seems promising in being safe across different treatment plans. However, since this trial is in the early stages, researchers are still collecting safety information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about AZD0486 for lymphoma because it introduces a unique approach to treatment through its various formulations. Unlike standard therapies, which often involve traditional chemotherapy and targeted drugs, AZD0486 can be delivered either as a subcutaneous injection or an intravenous infusion. This flexibility in administration could improve patient comfort and adaptability. Additionally, when combined with the drug acalabrutinib, AZD0486 may enhance therapeutic effects for certain lymphoma types, potentially offering more effective outcomes than current options. Furthermore, its combination with R-CHOP, a standard chemotherapy regimen, could lead to synergistic effects, increasing the potential for better responses in patients with lymphoma.

What evidence suggests that this trial's treatments could be effective for lymphoma?

Research has shown that AZD0486 may help treat certain blood cancers, such as Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL), especially when other treatments have failed. In this trial, participants with CLL/SLL may receive AZD0486 either as monotherapy or combined with acalabrutinib. For Mantle Cell Lymphoma (MCL), AZD0486 is being tested as monotherapy. Early studies showed a high success rate, with 96% of patients responding to the treatment and 85% achieving complete remission. In Large B-cell Lymphoma (LBCL), AZD0486 is being tested with a common chemotherapy treatment called R-CHOP to determine if it improves outcomes. These findings suggest that AZD0486 could be a promising option for treating blood cancers. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with certain types of blood cancers, like lymphoma and leukemia. They should be able to perform daily activities (ECOG 0-2) and use contraception. Specific groups need different prior treatments: one must have had at least two therapies including BTKi and BCL2i; another can join if sensitive to BTKi after one therapy.

Inclusion Criteria

I can care for myself and am up and about more than 50% of my waking hours.

I will use birth control during and for 6 months after treatment.

My lymphocyte count is below 10,000.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive AZD0486 as monotherapy or in combination with other anticancer agents

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 years 4 months

What Are the Treatments Tested in This Trial?

Interventions

• AZD0486

Trial Overview The study tests AZD0486 alone or with other cancer drugs (Vincristine, Doxorubicin, Prednisone, Cyclophosphamide, Acalabrutinib, Rituximab) in patients with mature B-cell malignancies. It aims to find out how safe and effective these combinations are against the disease.

How Is the Trial Designed?

Group I: Substudy 3 (LBCL): AZD0486 + R-CHOP Experimental Treatment 6 Interventions

Participants will receive AZD0486 as IV infusion in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy.

Group II: Substudy 2 (RR MCL): Cohort 2C (AZD0486 Monotherapy) Experimental Treatment 1 Intervention

Participants will receive AZD0486 monotherapy as IV infusion.

Group III: Substudy 2 (RR MCL): Cohort 2A (AZD0486 Monotherapy) Experimental Treatment 1 Intervention

Participants will receive AZD0486 monotherapy as SC injection.

Group IV: Substudy 1 (RR CLL/SLL): Cohort 1C (AZD0486 Monotherapy) Experimental Treatment 1 Intervention

Participants will receive AZD0486 monotherapy as intravenous (IV) infusion.

Group V: Substudy 1 (RR CLL/SLL): Cohort 1B (AZD0486 + Acalabrutinib) Experimental Treatment 2 Interventions

Participants will receive AZD0486 as SC injection. Participants will receive acalabrutinib tablet orally twice daily.

Group VI: Substudy 1 (RR CLL/SLL): Cohort 1A (AZD0486 Monotherapy) Experimental Treatment 1 Intervention

Participants will receive AZD0486 monotherapy as subcutaneous (SC) injection.

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS7083

SOUNDTRACK-E: A phase 1/2, open-label, multicenter ... This study is the first to evaluate SC AZD0486, and the first to evaluate AZD0486 in chronic lymphocytic leukemia (CLL). Methods: SOUNDTRACK-E ( ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06564038

NCT06564038 | A Study of AZD0486 Monotherapy or in ... The purpose of this study is to assess the safety and efficacy of AZD0486 administered as monotherapy or in combination with other anticancer agents.

3. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D7407C00001

A Study of AZD0486 Monotherapy or in Combination with ... The purpose of this study is to assess the safety and efficacy of AZD0486 administered as monotherapy or in combination with other anticancer agents

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31876911/

Acalabrutinib monotherapy in patients with relapsed/refractory ... This updated and expanded study confirms the efficacy, durability of response, and long-term safety of acalabrutinib, justifying its further investigation.

5. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effectiveness-of-azd0486-alone-or-with-other-drugs-for-adults-with-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma-mantle-cell-lymphoma-or-large-b-cell-lymphoma/

Study on the Safety and Effectiveness of AZD0486 Alone or ... This clinical trial is focused on studying certain blood cancers, specifically Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, ...

6. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2024/calquence-acalabrutinib-plus-chemoimmunotherapy-reduced-the-risk-of-disease-progression-or-death-by-27-percentage-vs-standard-of-care-in-patients-with-untreated-mantle-cell-lymphoma-in-echo-phase-iii-trial.html

CALQUENCE® (acalabrutinib) plus chemoimmunotherapy ... Results showed the CALQUENCE combination regimen reduced the risk of disease progression or death by 27% compared to standard-of-care chemoimmunotherapy.