NCT06564038

Brief 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

Trial Health

88
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
408

participants targeted

Target at P75+ for phase_1

Timeline
36mo left

Started Jan 2025

Longer than P75 for phase_1

Geographic Reach
13 countries

64 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress31%
Jan 2025Jun 2029

First Submitted

Initial submission to the registry

August 19, 2024

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 21, 2024

Completed
5 months until next milestone

Study Start

First participant enrolled

January 30, 2025

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 28, 2028

Expected
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 11, 2029

Last Updated

June 10, 2026

Status Verified

June 1, 2026

Enrollment Period

3.1 years

First QC Date

August 19, 2024

Last Update Submit

June 9, 2026

Conditions

Keywords

IgG4 fully human CD19xCD3 bispecific T-cell engagerB cell lymphomaSubcutaneousAcalabrutinibPrednisoneRituximabCyclophosphamideVincristineDoxorubicinSurovatamig

Outcome Measures

Primary Outcomes (2)

  • Number of Participants with Adverse Events, Serious Adverse Events and Adverse Events of Special Interest

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

    Up to 2 months

Secondary Outcomes (11)

  • Overall Response Rate (ORR)

    Up to 6 years 4 months

  • Complete Response (CR) Rate

    Up to 6 years 4 months

  • Duration of Response (DoR)

    Up to 6 years 4 months

  • Maximum Observed Concentration (Cmax)

    Up to 90 days after last dose

  • Area Under the Concentration-time Curve (AUC)

    Up to 90 days after last dose

  • +6 more secondary outcomes

Study Arms (7)

Substudy 1 (RR CLL/SLL): Cohort 1A (Surovatamig Monotherapy)

EXPERIMENTAL

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

Drug: Surovatamig

Substudy 1 (RR CLL/SLL): Cohort 1B (Surovatamig + Acalabrutinib)

EXPERIMENTAL

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

Drug: SurovatamigDrug: Acalabrutinib

Substudy 1 (RR CLL/SLL): Cohort 1C (Surovatamig Monotherapy)

EXPERIMENTAL

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

Drug: Surovatamig

Substudy 2 (RR MCL): Cohort 2A (Surovatamig Monotherapy)

EXPERIMENTAL

Participants will receive surovatamig monotherapy as SC injection.

Drug: Surovatamig

Substudy 2 (RR MCL): Cohort 2C (Surovatamig Monotherapy)

EXPERIMENTAL

Participants will receive surovatamig monotherapy as IV infusion.

Drug: Surovatamig

Substudy 3 (LBCL): Cohort 3A 2SUD (Surovatamig + RCHOP)

EXPERIMENTAL

Participants will receive surovatamig as IV infusion with a 2SUD (double step-up dosing) schedule for priming in combination with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy.

Drug: SurovatamigDrug: Prednisone (or equivalent)Drug: RituximabDrug: CyclophosphamideDrug: VincristineDrug: Doxorubicin

Substudy 3 (LBCL): Cohort 3B 3SUD (Surovatamig + RCHOP)

EXPERIMENTAL

Participants will receive surovatamig as IV infusion with a 3SUD (triple step-up dosing) schedule for priming in combination with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy.

Drug: SurovatamigDrug: Prednisone (or equivalent)Drug: RituximabDrug: CyclophosphamideDrug: VincristineDrug: Doxorubicin

Interventions

Surovatamig will be administered as either SC injection or IV infusion.

Also known as: AZD0486, TNB-486
Substudy 1 (RR CLL/SLL): Cohort 1A (Surovatamig Monotherapy)Substudy 1 (RR CLL/SLL): Cohort 1B (Surovatamig + Acalabrutinib)Substudy 1 (RR CLL/SLL): Cohort 1C (Surovatamig Monotherapy)Substudy 2 (RR MCL): Cohort 2A (Surovatamig Monotherapy)Substudy 2 (RR MCL): Cohort 2C (Surovatamig Monotherapy)Substudy 3 (LBCL): Cohort 3A 2SUD (Surovatamig + RCHOP)Substudy 3 (LBCL): Cohort 3B 3SUD (Surovatamig + RCHOP)

Vincristine will be administered as IV infusion as per standard of care.

Substudy 3 (LBCL): Cohort 3A 2SUD (Surovatamig + RCHOP)Substudy 3 (LBCL): Cohort 3B 3SUD (Surovatamig + RCHOP)

Doxorubicin will be administered as IV infusion as per standard of care.

Substudy 3 (LBCL): Cohort 3A 2SUD (Surovatamig + RCHOP)Substudy 3 (LBCL): Cohort 3B 3SUD (Surovatamig + RCHOP)

Prednisone (or equivalent) will be administered either oral or IV infusion as per standard of care.

Substudy 3 (LBCL): Cohort 3A 2SUD (Surovatamig + RCHOP)Substudy 3 (LBCL): Cohort 3B 3SUD (Surovatamig + RCHOP)

Rituximab will be administered as IV infusion as per standard of care.

Substudy 3 (LBCL): Cohort 3A 2SUD (Surovatamig + RCHOP)Substudy 3 (LBCL): Cohort 3B 3SUD (Surovatamig + RCHOP)

Cyclophosphamide will be administered as IV infusion as per standard of care.

Substudy 3 (LBCL): Cohort 3A 2SUD (Surovatamig + RCHOP)Substudy 3 (LBCL): Cohort 3B 3SUD (Surovatamig + RCHOP)

Acalabrutinib will be administered orally

Substudy 1 (RR CLL/SLL): Cohort 1B (Surovatamig + Acalabrutinib)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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 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.
  • 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.
  • At least 1 measurable site as per Lugano.
  • Left ventricular ejection fraction (LVEF) ≥50%.
  • +9 more criteria

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (64)

Research Site

Boston, Massachusetts, 02215, United States

RECRUITING

Research Site

Hackensack, New Jersey, 07601, United States

RECRUITING

Research Site

New Brunswick, New Jersey, 08901, United States

RECRUITING

Research Site

New York, New York, 10029, United States

RECRUITING

Research Site

New York, New York, 10065, United States

WITHDRAWN

Research Site

Charlotte, North Carolina, 28204, United States

RECRUITING

Research Site

Charlotte, North Carolina, 28204, United States

NOT YET RECRUITING

Research Site

Columbus, Ohio, 43210, United States

RECRUITING

Research Site

Portland, Oregon, 97239, United States

RECRUITING

Research Site

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Research Site

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Research Site

Providence, Rhode Island, 02903, United States

RECRUITING

Research Site

Houston, Texas, 77030, United States

NOT YET RECRUITING

Research Site

Heidelberg, 3084, Australia

RECRUITING

Research Site

Melbourne, 3004, Australia

RECRUITING

Research Site

Nedlands, 6009, Australia

RECRUITING

Research Site

Beijing, 100044, China

RECRUITING

Research Site

Guangzhou, 510060, China

RECRUITING

Research Site

Jinan, 250013, China

WITHDRAWN

Research Site

Tianjin, 300060, China

RECRUITING

Research Site

Zhengzhou, 450008, China

RECRUITING

Research Site

Ostrava - Poruba, 708 52, Czechia

RECRUITING

Research Site

Prague, 12808, Czechia

RECRUITING

Research Site

Praha 2 - Nové Město, 12820, Czechia

RECRUITING

Research Site

Aalborg, 9000, Denmark

RECRUITING

Research Site

Aarhus N, 8200, Denmark

RECRUITING

Research Site

Copenhagen, 2100, Denmark

RECRUITING

Research Site

Odense C, 5000, Denmark

RECRUITING

Research Site

Clermont-Ferrand, 63000, France

NOT YET RECRUITING

Research Site

Montpellier, 34295, France

RECRUITING

Research Site

Paris, 75010, France

RECRUITING

Research Site

Saint-Cloud, 92210, France

RECRUITING

Research Site

Villejuif, 94805, France

RECRUITING

Research Site

Cologne, 50937, Germany

NOT YET RECRUITING

Research Site

Homburg, 66421, Germany

NOT YET RECRUITING

Research Site

Kiel, 24105, Germany

RECRUITING

Research Site

Mainz, 55131, Germany

NOT YET RECRUITING

Research Site

München, 81377, Germany

RECRUITING

Research Site

Würzburg, 97080, Germany

RECRUITING

Research Site

Bologna, 40138, Italy

NOT YET RECRUITING

Research Site

Milan, 20141, Italy

NOT YET RECRUITING

Research Site

Kōtoku, 135-8550, Japan

RECRUITING

Research Site

Matsuyama, 791-0280, Japan

RECRUITING

Research Site

Nagoya, 464-8681, Japan

RECRUITING

Research Site

Busan, 48108, South Korea

RECRUITING

Research Site

Seoul, 02841, South Korea

RECRUITING

Research Site

Seoul, 03080, South Korea

RECRUITING

Research Site

Seoul, 05505, South Korea

RECRUITING

Research Site

Seoul, 06351, South Korea

RECRUITING

Research Site

Seoul, 06591, South Korea

RECRUITING

Research Site

Barcelona, 8036, Spain

RECRUITING

Research Site

Madrid, 28034, Spain

RECRUITING

Research Site

Madrid, 28040, Spain

RECRUITING

Research Site

Palma de Mallorca, 7120, Spain

RECRUITING

Research Site

Santiago de Compostela, 15706, Spain

RECRUITING

Research Site

Valencia, 46026, Spain

RECRUITING

Research Site

Changhua, 500, Taiwan

RECRUITING

Research Site

Kaohsiung City, 83301, Taiwan

RECRUITING

Research Site

Tainan, 710, Taiwan

RECRUITING

Research Site

Taipei, 100, Taiwan

RECRUITING

Research Site

Derriford, PL6 5FP, United Kingdom

RECRUITING

Research Site

London, SE5 9RS, United Kingdom

RECRUITING

Research Site

Oxford, 0X3 7LJ, United Kingdom

RECRUITING

Research Site

Southampton, SO16 6YD, United Kingdom

RECRUITING

MeSH Terms

Conditions

Leukemia, B-CellLeukemia, Lymphocytic, Chronic, B-CellLymphoma, Mantle-CellLymphoma, B-Cell

Interventions

PrednisoneRituximabCyclophosphamideVincristineDoxorubicinacalabrutinib

Condition Hierarchy (Ancestors)

Leukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLymphoma, Non-HodgkinLymphoma

Intervention Hierarchy (Ancestors)

PregnadienediolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsAntibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsVinca AlkaloidsSecologanin Tryptamine AlkaloidsIndole AlkaloidsAlkaloidsHeterocyclic CompoundsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingIndolizidinesIndolizinesDaunorubicinAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicAminoglycosidesGlycosidesCarbohydrates

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 19, 2024

First Posted

August 21, 2024

Study Start

January 30, 2025

Primary Completion (Estimated)

February 28, 2028

Study Completion (Estimated)

June 11, 2029

Last Updated

June 10, 2026

Record last verified: 2026-06

Data Sharing

IPD Sharing
Will share

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via there quest portal Vivli.org. 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 approved.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
More information

Locations