Surovatamig as Consolidation Therapy in Participants With Chronic Lymphocytic Leukaemia or Small Lymphocytic Lymphoma With Unmutated Immunoglobulin Heavy Chain Variable (IGHV)

Browse trials for

• Leukemia, B-Cell 125
• Leukemia 5,446
• Lymphoma 5,585

Keywords

• Leukaemia
• Lymphoma
• Monoclonal IgG4 antibody
• Consolidation therapy
• Therapeutic benefit
• Induction therapy
• B-cell malignancy

Study arms

• Experimental
  Dose Optimisation and Safety run-in (DOSRI)- Surovatamig Dose 1

  Participants will receive Surovatamig Dose 1 subcutaneously (SC) for 6 cycles (each cycle is 28 days in length).

  Drug: Surovatamig

• Experimental
  DOSRI-Surovatamig Dose 2

  Participants will receive Surovatamig Dose 2 SC for 6 cycles (each cycle is 28 days in length).

  Drug: Surovatamig

• Experimental
  Phase III-Arm A: Surovatamig SC

  Participants will receive Surovatamig at RP3D subcutaneously for 6 cycles (each cycle is 28 days in length).

  Drug: Surovatamig

• No intervention
  Phase III-Arm B: Observation

  Participants will undergo observation for 24 weeks.

Interventions

• DrugSurovatamig

  Surovatamig will be administered as a subcutaneous injection.

  Also known as: TNB-486, AZD0486

Primary outcomes

1. DOSRI- Number of participants with adverse events (AEs) and Serious Adverse Events (SAEs)

   To assess the safety and tolerability of SC surovatamig as consolidation therapy using dose optimisation in CLL/SLL participants with uIGHV. Also, to determine the RP3D of SC surovatamig monotherapy as consolidation therapy in CLL/SLL participants with uIGHV.

   Time frame: Up to 5 years

2. Phase III- Progression Free Survival (PFS)

   PFS is defined as the time from date of randomisation until disease progression or death due to any cause, whichever occur first based on International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria, as assessed by independent review committee (IRC).

   Time frame: Until disease progression or death (up to 5 years)

3. DOSRI- Number of participants with study intervention discontinuations, dose reductions and dose delays due to AEs

   To assess the safety and tolerability of SC surovatamig as consolidation therapy using dose optimisation in CLL/SLL participants with uIGHV. Also, to determine the RP3D of SC surovatamig monotherapy as consolidation therapy in CLL/SLL participants with uIGHV.

   Time frame: Up to 5 years

Secondary outcomes

1. Objective Response Rate (ORR)

   ORR is defined as the proportion of participants achieving either a partial response (PR) or complete response (CR)/complete response with incomplete haematological recovery (CRi) based on response criteria iwCLL 2018, as assessed by IRC or investigator at any point during therapy/observation.

   Time frame: Up to 5 years

2. Complete Response rate (CR rate)

   CR rate is defined as the proportion of participants achieving a CR or CRi as best response based on response criteria for iwCLL 2018.

   Time frame: Up to 5 years

3. Duration of response (DoR)

   The DoR is defined as the time from the date of first documented response until date of documented progression based on response criteria for iwCLL 2018.

   Time frame: Up to 5 years

4. DOSRI- PFS

   PFS for Safety Run-in phase is defined as the time from first dose until the date of documented progression or death due to any cause whichever comes first, based on iwCLL 2018 criteria.

   Time frame: Until disease progression or death (up to 5 years)

5. Overall Survival (OS)

   OS is defined as the time from first dose until death due to any cause.

   Time frame: Up to 5 years

6. Serum concentrations of Surovatamig

   To characterise the serum concentration of SC surovatamig as consolidation therapy in CLL/SLL participants with uIGHV.

   Time frame: At pre-defined intervals from date offirst dose (C1D1) up to 30 days from last dose (approximately 5 years)

7. Maximum concentration observed (Cmax)

   To characterise the pharmacokinetics (PK) of SC surovatamig as consolidation therapy in CLL/SLL participants with uIGHV.

   Time frame: At pre-defined intervals from date of first dose up to 30 days from last dose (approximately 5 years)

8. Time to Maximum Concentration (tmax)

   To characterise the PK of SC surovatamig as consolidation therapy in CLL/SLL participants with uIGHV.

   Time frame: At pre-defined intervals from date of first dose up to 30 days from last dose (approximately 5 years)

9. Trough concentration (Ctrough)

   To characterise the PK of SC surovatamig as consolidation therapy in CLL/SLL participants with uIGHV.

   Time frame: At pre-defined intervals from date of first dose up to 30 days from last dose (approximately 5 years)

10. Number of participants with Anti-drug antibodies (ADA)

    DOSRI- To evaluate the immunogenicity of SC surovatamig as consolidation therapy in CLL/SLL participants with uIGHV. Phase III- To determine the immunogenicity of SC surovatamig in CLL/SLL participants with uIGHV.

    Time frame: At predefined intervals from the date of first dose to approximately 5 years

11. Phase III- PFS

    PFS is defined as the time from date of randomisation until disease progression or death due to any cause , whichever comes first based on iwCLL 2018 criteria, as assessed by investigator.

    Time frame: Until disease progression or death (up to 5 years)

12. Phase III- Number of participants with AEs and SAEs

    To assess safety and tolerability of SC surovatamig compared to observation in CLL/SLL participants with uIGHV.

    Time frame: Up to 5 years

Individual participant data

Plan to share: Yes — Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request 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 shared.

Supporting information: Study protocol, Sap