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
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
Detailed description
This is open-label, multi-center study to evaluate the safety and preliminary efficacy of surovatamig 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
Arms & interventions
- DrugSurovatamig
Surovatamig will be administered as either SC injection or IV infusion.
- DrugPrednisone (or equivalent)
Prednisone (or equivalent) will be administered either oral or IV infusion as per standard of care.
- DrugRituximab
Rituximab will be administered as IV infusion as per standard of care.
- DrugCyclophosphamide
Cyclophosphamide will be administered as IV infusion as per standard of care.
- DrugVincristine
Vincristine will be administered as IV infusion as per standard of care.
- DrugDoxorubicin
Doxorubicin will be administered as IV infusion as per standard of care.
- DrugAcalabrutinib
Acalabrutinib will be administered orally
Outcome measures
Primary
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.
Time frame: 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.
Time frame: Up to 2 months
Secondary
Overall Response Rate (ORR)
Time frame: Up to 6 years 4 months
Complete Response (CR) Rate
Time frame: Up to 6 years 4 months
Duration of Response (DoR)
Time frame: Up to 6 years 4 months
Maximum Observed Concentration (Cmax)
Time frame: Up to 90 days after last dose
Area Under the Concentration-time Curve (AUC)
Time frame: Up to 90 days after last dose
Minimum Observed Concentration (Cmin)
Time frame: Up to 90 days after last dose
Time to Reach Maximum Concentration (tmax)
Time frame: Up to 90 days after last dose
Trough Plasma Concentration (Ctrough)
Time frame: Up to 90 days after last dose
Half Life (t1/2) of surovatamig
Time frame: Up to 90 days after last dose
Clearance (CL) of surovatamig
Time frame: Up to 90 days after last dose
Number of Participants with Anti-drug Antibody (ADA) for surovatamig
Time frame: Up to 90 days after last dose
Eligibility criteria
Study locations (13)
Research Site
Boston, Massachusetts, 02215
Research Site
Hackensack, New Jersey, 07601
Research Site
New Brunswick, New Jersey, 08901
Research Site
New York, New York, 10029
Research Site
New York, New York, 10065
Research Site
Charlotte, North Carolina, 28204
Research Site
Charlotte, North Carolina, 28204
Research Site
Columbus, Ohio, 43210
Research Site
Portland, Oregon, 97239
Research Site
Philadelphia, Pennsylvania, 19104
Research Site
Pittsburgh, Pennsylvania, 15232
Research Site
Providence, Rhode Island, 02903
Research Site
Houston, Texas, 77030