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

Official title

A Phase III, Randomised, Open-label, Multicentre, Study of Surovatamig as Consolidation Therapy Versus Observation After First-line Induction Therapy in Participants With Chronic Lymphocytic Leukaemia or Small Lymphocytic Lymphoma With Unmutated IGHV (SOUNDTRACK-C1)

Overview

The purpose of this study is to evaluate the therapeutic benefit and safety of subcutaneous (SC) Surovatamig monotherapy as consolidation therapy in patients with Chronic Lymphocytic Leukaemia (CLL)/ Small Lymphocytic Lymphoma (SLL) with unmutated IGHV (uIGHV).

Detailed description

This is a Phase III global, randomised, open-label, multicentre study. The study will consist of 2 sequential parts- the Dose Optimisation and Safety Run-in part and the Phase-III part.

During the dose optimisation and safety run-in part, Surovatamig will be initiated in 2 dose levels. This part will help to determine the recommended phase III dose (RP3D) of Surovatamig to be used in Phase III part. Phase III would comprise of 2 arms, Arm A where the Surovatamig dose (RP3D) will be administered as a consolidation therapy (post standard of care \[SOC\] induction therapy) and Arm B where participants will be observed. In Phase 3 participants will be randomized in a 1:1 ratio to Arm A or Arm B.

Interventions

• Drug Surovatamig
  Surovatamig will be administered as a subcutaneous injection.

Primary outcome measures

• DOSRI- Number of participants with adverse events (AEs) and Serious Adverse Events (SAEs) [Time frame: Up to 5 years]
• Phase III- Progression Free Survival (PFS) [Time frame: Until disease progression or death (up to 5 years)]
• DOSRI- Number of participants with study intervention discontinuations, dose reductions and dose delays due to AEs [Time frame: Up to 5 years]

Secondary outcome measures (12)

• Objective Response Rate (ORR) [Time frame: Up to 5 years]
• Complete Response rate (CR rate) [Time frame: Up to 5 years]
• Duration of response (DoR) [Time frame: Up to 5 years]
• DOSRI- PFS [Time frame: Until disease progression or death (up to 5 years)]
• Overall Survival (OS) [Time frame: Up to 5 years]
• Serum concentrations of Surovatamig [Time frame: At pre-defined intervals from date offirst dose (C1D1) up to 30 days from last dose (approximately 5 years)]
• Maximum concentration observed (Cmax) [Time frame: At pre-defined intervals from date of first dose up to 30 days from last dose (approximately 5 years)]
• Time to Maximum Concentration (tmax) [Time frame: At pre-defined intervals from date of first dose up to 30 days from last dose (approximately 5 years)]
• Trough concentration (Ctrough) [Time frame: At pre-defined intervals from date of first dose up to 30 days from last dose (approximately 5 years)]
• Number of participants with Anti-drug antibodies (ADA) [Time frame: At predefined intervals from the date of first dose to approximately 5 years]
• Phase III- PFS [Time frame: Until disease progression or death (up to 5 years)]
• Phase III- Number of participants with AEs and SAEs [Time frame: Up to 5 years]

Eligibility criteria

Inclusion criteria

• Documented diagnosis of CLL/SLL with genomic features defined by unmutated IGHV.
• Treatment received and response at the end of 1L (first-line) finite therapy.
• Participants with SLL (except those in CR in Phase III part) must have measurable disease (nodal or extranodal) with at least one measurable target lesion.
• ECOG performance status of 0 to 2.
• Adequate haematologic, liver, renal and cardiac function.
• Female participants: must be either women not of childbearing potential or must use a highly effective form of contraception.
• Male participants who intend to be sexually active with females of childbearing potential must agree to use barrier contraception (eg, condoms).

Exclusion criteria

• Suspected or confirmed transformation of CLL/SLL to a more aggressive form of lymphoma (ie, Richter's transformation, prolymphocytic leukaemia, or DLBCL).
• Evidence of active or history of Central Nervous System (CNS) involvement by CLL/SLL.
• History of or ongoing confirmed progressive multifocal leukoencephalopathy.
• Participants who have any concurrent or history of malignancy.
• Participants with:
• Active or uncontrolled infection (including Epstein-Barr virus-EBV) requiring systemic therapy.
• Participants with known history of Heamophagocytic lymphohistiocytosis (HLH).
• Human Immunodeficiency Virus (HIV) infection, or participants with chronic or active infection with Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV).
• Major cardiac abnormalities.
• Prior CLL/SLL-specific therapies.
• Requires chronic immunosuppressive therapy for active autoimmune/inflammatory condition or prior allogeneic stem cell or solid organ transplant.
• Major surgical procedure.
• Known hypersensitivity to surovatamig or any of the excipients of the product.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United Kingdom · 9 centers

• Research Site — Edinburgh
• Research Site — Hampshire
• Research Site — Leeds
• Research Site — London
• Research Site — London
• Research Site — Manchester
• Research Site — Nottingham
• Research Site — Oxford
• … and 1 more center

Canada · 8 centers

• Research Site — Calgary
• Research Site — Vancouver
• Research Site — Halifax
• Research Site — Hamilton
• Research Site — Toronto
• Research Site — Montreal
• Research Site — Montreal
• Research Site — Québec

Turkey (Türkiye) · 7 centers

• Research Site — Adapazarı
• Research Site — Antalya
• Research Site — Istanbul
• Research Site — Istanbul
• Research Site — Istanbul
• Research Site — Kocaeli
• Research Site — Mezitli

Australia · 6 centers

• Research Site — Adelaide
• Research Site — Fitzroy
• Research Site — Heidelberg
• Research Site — Nedlands
• Research Site — Perth
• Research Site — Rockingham

Identifiers

NCT: NCT07509151 · D7409C00001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗