Recruiting
Phase 1/2
A Study of AZD0486 Monotherapy or in Combination With Other Anti-Cancer Agents for Mature B-Cell Malignancies
Condition(s) studied
Chronic Lymphocytic LeukaemiaSmall Lymphocytic LymphomaMantle-cell LymphomaLarge B-cell LymphomaB-cell Non-Hodgkin Lymphoma
Investigational drug(s) / intervention(s)
SurovatamigPrednisone (or equivalent)RituximabCyclophosphamideVincristineDoxorubicinAcalabrutinib
Surovatamig: Surovatamig will be administered as either SC injection or IV infusion.
Prednisone (or equivalent): Prednisone (or equivalent) will be administered either oral or IV infusion as per standard of care.
Rituximab: Rituximab will be administered as IV infusion as per standard of care.
Cyclophosphamide: Cyclophosphamide will be administered as IV infusion as per standard of care.
Vincristine: Vincristine will be administered as IV infusion as per standard of care.
Doxorubicin: Doxorubicin will be administered as IV infusion as per standard of care.
Acalabrutinib: Acalabrutinib will be administered orally
Study 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
Eligibility
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Primary outcome measure(s)
- Number of Participants with Adverse Events, Serious Adverse Events and Adverse Events of Special Interest — 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.
- Number of Participants with Dose Limiting Toxicity (DLTs) — Up to 2 months
Safety and tolerability of surovatamig as monotherapy and in combination with other anticancer agents across mature B-cell malignancies.
Trial sites (65)
| Facility | City | Region | Status |
| Research Site |
Boston |
Massachusetts |
Recruiting |
| Research Site |
Hackensack |
New Jersey |
Recruiting |
| Research Site |
New Brunswick |
New Jersey |
Recruiting |
| Research Site |
New York |
New York |
Recruiting |
| Research Site |
New York |
New York |
Withdrawn |
| Research Site |
Charlotte |
North Carolina |
Recruiting |
| Research Site |
Charlotte |
North Carolina |
Not Yet Recruiting |
| Research Site |
Columbus |
Ohio |
Recruiting |
| Research Site |
Portland |
Oregon |
Recruiting |
| Research Site |
Philadelphia |
Pennsylvania |
Recruiting |
| Research Site |
Pittsburgh |
Pennsylvania |
Recruiting |
| Research Site |
Providence |
Rhode Island |
Recruiting |
| Research Site |
Houston |
Texas |
Not Yet Recruiting |
| Research Site |
Heidelberg |
Australia |
Recruiting |
| Research Site |
Melbourne |
Australia |
Recruiting |
| Research Site |
Nedlands |
Australia |
Recruiting |
| Research Site |
Beijing |
China |
Recruiting |
| Research Site |
Guangzhou |
China |
Recruiting |
| Research Site |
Jinan |
China |
Withdrawn |
| Research Site |
Tianjin |
China |
Recruiting |
| Research Site |
Zhengzhou |
China |
Recruiting |
| Research Site |
Ostrava - Poruba |
Czechia |
Recruiting |
| Research Site |
Prague |
Czechia |
Recruiting |
| Research Site |
Praha 2 - Nové Město |
Czechia |
Recruiting |
| Research Site |
Aalborg |
Denmark |
Recruiting |
| Research Site |
Aarhus N |
Denmark |
Recruiting |
| Research Site |
Copenhagen |
Denmark |
Recruiting |
| Research Site |
Odense C |
Denmark |
Recruiting |
| Research Site |
Clermont-Ferrand |
France |
Not Yet Recruiting |
| Research Site |
Montpellier |
France |
Recruiting |
| Research Site |
Paris |
France |
Recruiting |
| Research Site |
Saint-Cloud |
France |
Recruiting |
| Research Site |
Villejuif |
France |
Recruiting |
| Research Site |
Cologne |
Germany |
Not Yet Recruiting |
| Research Site |
Homburg |
Germany |
Not Yet Recruiting |
| Research Site |
Kiel |
Germany |
Recruiting |
| Research Site |
Mainz |
Germany |
Not Yet Recruiting |
| Research Site |
München |
Germany |
Recruiting |
| Research Site |
Würzburg |
Germany |
Recruiting |
| Research Site |
Bologna |
Italy |
Not Yet Recruiting |
+ 25 more sites — see the full list on the official registry below.