A Study of AZD0486 Monotherapy or in Combination With Other Anti-Cancer Agents for Mature B-Cell Malignancies

NCT06564038
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Phase
Phase 1/Phase 2
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Recruitment status
Recruiting
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Participants
408
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Lead sponsor
AstraZeneca
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Start date
2025-01-30
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Number of sites
64
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Summary
The purpose of this study is to assess the safety and efficacy of surovatamig (formerly AZD0486) administered as monotherapy or in combination with other anticancer agents in participants with hematological malignancies
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Acronym
Soundtrack-E
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Short title
A Study of AZD0486 Monotherapy or in Combination With Other Anti-Cancer Agents for Mature B-Cell Malignancies
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Official title
A Phase I/II Open-Label Multi-Centre Master Protocol to Evaluate the Safety and Efficacy of AZD0486 Monotherapy or in Combination With Other Anticancer Agents in Participants With Mature B-Cell Malignancies
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1/Phase 2
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Study type
Interventional
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Completion date
2029-06-11
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First posted
2024-08-21
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Registry last updated
2026-08-12
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Primary completion date
2029-06-11
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Start date
2025-01-30
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Participants
408
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Participant count basis
Estimated
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Planned participants
408
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Protocol amendments
3
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Number of sites
64
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
AstraZeneca
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06564038
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ClinicalTrials.gov ID
NCT06564038
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Number of Participants with Adverse Events, Serious Adverse Events and Adverse Events of Special Interest

    Timeframe: Up to 6 years 4 months

    Safety and tolerability of surovatamig as monotherapy and in combination with other anticancer agents across mature B-cell malignancies.

  2. Number of Participants with Dose Limiting Toxicity (DLTs)

    Timeframe: Up to 2 months

    Safety and tolerability of surovatamig as monotherapy and in combination with other anticancer agents across mature B-cell malignancies.

  1. Overall Response Rate (ORR)

    Timeframe: Up to 6 years 4 months

    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 either PR or CR based on Lugano 2014 Response Criteria by investigator assessment (substudies 2 and 3).

  2. Complete Response (CR) Rate

    Timeframe: Up to 6 years 4 months

    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).

  3. Duration of Response (DoR)

    Timeframe: Up to 6 years 4 months

    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).

  4. Maximum Observed Concentration (Cmax)

    Timeframe: Up to 90 days after last dose

    The PK (Cmax) of surovatamig as monotherapy and in combination with other anti-cancer agents will be evaluated.

  5. Area Under the Concentration-time Curve (AUC)

    Timeframe: Up to 90 days after last dose

    The PK (AUC) of surovatamig as monotherapy and in combination with other anti-cancer agents will be evaluated.

  6. Minimum Observed Concentration (Cmin)

    Timeframe: Up to 90 days after last dose

    The PK (Cmin) of surovatamig as monotherapy and in combination with other anti-cancer agents will be evaluated.

  7. Time to Reach Maximum Concentration (tmax)

    Timeframe: Up to 90 days after last dose

    The PK (tmax) of surovatamig as monotherapy and in combination with other anti-cancer agents will be evaluated.

  8. Trough Plasma Concentration (Ctrough)

    Timeframe: Up to 90 days after last dose

    The PK (Ctrough) of surovatamig as monotherapy and in combination with other anti-cancer agents will be evaluated.

  9. Half Life (t1/2) of surovatamig

    Timeframe: Up to 90 days after last dose

    The PK (t1/2) of surovatamig as monotherapy and in combination with other anti-cancer agents will be evaluated.

  10. Clearance (CL) of surovatamig

    Timeframe: Up to 90 days after last dose

    The PK (CL) of surovatamig as monotherapy and in combination with other anti-cancer agents will be evaluated.

  11. Number of Participants with Anti-drug Antibody (ADA) for surovatamig

    Timeframe: Up to 90 days after last dose

    The incidence of immunogenicity of SC surovatamig as monotherapy and in combination with other anti-cancer agents will be evaluated.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

Master Inclusion Criteria applicable to all substudies:

  • 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.

Substudy 1 Specific Inclusion Criteria:

  • 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 lymphocyte count (ALC) <25000 cells/mcL.
  • 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.

Substudy 2 Specific Inclusion Criteria:

  • MCL diagnosis per WHO.
  • Clinical Stage II, III, or IV by Ann Arbor Classification.
  • At least 1 measurable site per Lugano.
  • ALC < 25000 cells/mcL.
  • Cohort 2A and 2C: Relapse or progressed after 2 or more lines of therapy including BTKi.

Substudy 3 Specific Inclusion Criteria:

  • At least 1 measurable site as per Lugano.

  • Left ventricular ejection fraction (LVEF) ≥50%.

  • Participant must be no older than 79 years of age at the time of signing ICF.

  • Contraception at least 90 days after last dose of surovatamig or 4 months after last dose of vincristine, and 6 months after the last dose of cyclophosphamide, or doxorubicin.

  • Cohort 3A:

    1. Histologically confirmed diagnosis of previously untreated large B-cell Lymphoma (LBCL) per WHO 2022.
    2. R/R B-NHL after at least 1 prior lines of systemic therapy.
    3. International Prognostic Index (IPI) 2-5.

  • Cohort 3B:

    1. Histologically confirmed diagnosis of previously untreated large B-cell Lymphoma (LBCL) per WHO 2022.
    2. IPI score of 2 to 5.

Master Exclusion Criteria applicable to all substudies:

  • 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 systemic 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.
  • Active, significant, uncontrolled infection or autoimmune disease requiring systemic therapy including participants with known history of haemophagocytic lymphohistiocytosis (HLH).

Substudy 1 Specific Exclusion Criteria:

  • CLL/SLL transformation to more aggressive form of lymphoma.
  • Cohort 1B: bleeding diathesis, CYP3A inhibitor or inducer, history of ICH or stroke within 24 weeks, GI malabsorption, receiving vitamin K antagonist.

Substudy 3 Specific Exclusion Criteria:

  • Mediastinal grey-zone lymphoma, Burkitt, Richter's transformation, primary effusion large B-cell lymphoma (LBCL).
  • Cumulative dose of anthracycline >150 mg/m2.
Sources for eligibility
clinicaltrials.gov

  • Research SiteBoston, United StatesRecruiting
  • Research SiteHackensack, United StatesRecruiting
  • Research SiteNew Brunswick, United StatesRecruiting
  • Research SiteNew York, United StatesRecruiting
  • Research SiteNew York, United StatesWithdrawn
  • Research SiteCharlotte, United StatesRecruiting
  • Research SiteCharlotte, United StatesNot yet recruiting
  • Research SiteColumbus, United StatesRecruiting
  • Research SitePortland, United StatesRecruiting
  • Research SitePhiladelphia, United StatesRecruiting
  • Research SitePittsburgh, United StatesRecruiting
  • Research SiteProvidence, United StatesRecruiting
  • Research SiteHouston, United StatesNot yet recruiting
  • Research SiteHeidelberg, AustraliaRecruiting
  • Research SiteMelbourne, AustraliaRecruiting
  • Research SiteNedlands, AustraliaRecruiting
  • Research SiteBeijing, ChinaRecruiting
  • Research SiteGuangzhou, ChinaRecruiting
  • Research SiteJinan, ChinaWithdrawn
  • Research SiteTianjin, ChinaRecruiting
  • Research SiteZhengzhou, ChinaRecruiting
  • Research SiteOstrava - Poruba, CzechiaRecruiting
  • Research SitePrague, CzechiaRecruiting
  • Research SitePraha 2 - Nové Město, CzechiaRecruiting
  • Research SiteAalborg, DenmarkRecruiting

And 39 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

Other registry identifiers

  • 2024-515034-33-00
Sources for references
clinicaltrials.gov

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