Not Yet RecruitingPhase 3ACTRN12626000311358

An ALLG international randomised phase III trial of Surovatamig versus radiotherapy with or without Rituximab in limited stage nodal Follicular Lymphoma

Sponsor

Australasian Leukaemia and Lymphoma Group

Enrollment

168 participants

Start Date

Jan 12, 2027

Study Type

Interventional

Conditions

Follicular Lymphoma

Summary

What the study is about: This study will evaluate whether surovatamig, a novel CD19 × CD3 bispecific T-cell engager, can improve outcomes for people with previously untreated, limited-stage nodal follicular lymphoma (FL). The trial will compare surovatamig with the current standard of care: involved-site radiotherapy (ISRT) with or without rituximab. The aim is to determine whether surovatamig can produce deeper and more durable responses, reduce the risk of disease relapse, and improve event-free survival. Who is it for: This study is for adults aged 18 years or older who have: 1. Histologically confirmed classical follicular lymphoma (Grade 1–3a), Ann Arbor stage I or II nodal, non-bulky disease ( less or equal to 7 cm) 2. PET-positive, measurable disease 3. No prior lymphoma-directed therapy Study details: This is an international, Phase III randomised clinical trial. Participants will be randomised 1:1 on either Surovatamig (6 doses over 12 weeks using a triple step-up dosing schedule) or to the standard of care treatment (Involved-Site Radiotherapy (24 Gy) with or without 6 doses of rituximab, according to each site's predefined standard). Participants will be followed up for 10 years after treatment to assess long-term outcomes. A total of 168 participants will be enrolled across Australia, New Zealand, the United Kingdom, Ireland and Nordic countries. Of these, 60 participants are expected from Australian and New Zealand sites. What is hoped from it: If successful, surovatamig could represent a new standard of care for patients with early-stage nodal follicular lymphoma that is highly effective, well-tolerated, non-radiation frontline option for patients with limited-stage FL.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria22

Patients or their legally authorised representative must voluntarily sign and date an informed consent form (ICF), approved by a Human Research Ethics Committee (HREC), prior to the initiation of any screening or trial-specific procedures.
Provide samples for optional genetic research that supports the Genomic Initiative.
Are willing and able to comply with procedures required in this protocol.
Age 18 years and older at the time of signing the informed consent form (ICF).
Must have histologically confirmed classical follicular lymphoma (FL) (previously Grade 1 to 3a FL) at the most recent representative tumour biopsy based on the local pathology report, according to the 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours.
Must have Ann Arbor Stage I or II, nodal, non-bulky disease (maximum tumour diameter less than or equal to 7 cm).
Previously untreated disease (no prior systemic lymphoma-directed therapies).
Has one or more target lesions:
a. A positron emission tomography/computed tomography (PET/CT) scan demonstrating PET-positive lesion(s), and
b. At least one measurable nodal lesion (long axis over 1.5 cm) or at least one measurable extra-nodal lesion (long axis over 1.0 cm) on computed tomography (CT) scan or magnetic resonance imaging (MRI).
Eastern Cooperative Oncology Group (ECOG) performance status 0–2.
Patient must have adequate renal and liver function, unless values meeting the following criteria are related to lymphoma:
a) Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) less or equal to 3.0 × upper limit of normal (ULN)
b) Total bilirubin less or equal to 1.5 × ULN; subjects with Gilbert’s syndrome may have total bilirubin greater than 1.5 × ULN, but conjugated (direct) bilirubin must be less or equal to 2 × ULN
c) Estimated creatinine clearance (CrCl) greater or equal to 45 mL/min (as calculated by the Cockcroft–Gault formula)
Patient must have adequate haematologic function:
a) Absolute neutrophil count (ANC) greater or equal to 1.0 × 10^?/L
b) Haemoglobin greater or equal to 8 g/dL
c) Platelet count greater or equal to 75 × 10^?/L
Patients of child-bearing potential must have a negative serum pregnancy test 10 to 14 days prior to randomisation and again within 24 hours prior to Cycle 1 Day 1 (C1D1). The pregnancy test must be sensitive to at least 25 mIU/mL.
Women of child-bearing potential must agree to practise at least two protocol-specified methods of birth control, effective from 28 days prior to randomisation through at least 12 months after the last dose of trial drug. Female patients of non-child-bearing potential do not need to use birth control.
Male patients who are sexually active with female partners of child-bearing potential must agree, from 28 days prior to randomisation through 12 months after the last dose of trial drug, to practise the protocol-specified contraception, particularly using a latex or synthetic condom every time they have sexual intercourse with a partner of reproductive potential, even if they have undergone a successful vasectomy.

Exclusion Criteria33

Has a history of prior systemic or radiotherapy therapy for follicular lymphoma (FL).
Has prior or current follicular large B-cell lymphoma (World Health Organization [WHO] 2022 classification), formerly follicular lymphoma Grade 3B (WHO 2016 classification), histologic transformation to diffuse large B-cell lymphoma (DLBCL) or other aggressive lymphomas.
Known or suspected central nervous system (CNS) involvement at screening based on clinical presentation or imaging findings.
A history of severe allergic or anaphylactic reactions to any component or excipient of AZD486.
Has had major surgery within 14 days prior to the first dose of trial intervention (excluding biopsies) or anticipation of the need for major surgery during trial intervention.
Clinically significant cardiovascular disease, such as:
a. Myocardial infarction within less or equal to 12 weeks or stroke within 6 months prior to randomisation
b. Screening 12-lead electrocardiogram (ECG) showing a baseline QT interval as corrected by Frederica’s formula (QTcF) over 480 msec
c. The following conditions within 3 months prior to randomisation:
i. Uncontrolled unstable angina
ii. New York Heart Association (NYHA) Class III–IV congestive heart failure
iii. Uncontrolled life-threatening cardiac arrhythmia
iv. Other clinically significant ECG abnormalities in the opinion of the investigator
History or presence of clinically relevant CNS pathology (based on investigator assessment) such as epilepsy, seizure, paresis, aphasia, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, or psychosis.
Active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) requiring systemic therapy or antibiotics within 2 weeks prior to randomisation.
Human immunodeficiency virus (HIV) infection unless:
a. Patients on effective antiretroviral therapy with undetectable viral load within 6 months prior to trial entry are eligible
b. HIV ribonucleic acid (RNA) will be monitored during the trial as clinically indicated
Active hepatitis B infection (detectable hepatitis B virus [HBV] deoxyribonucleic acid (DNA) or hepatitis B surface antigen [HBsAg]).
a. Patients who are hepatitis B core antibody [HBcAb] positive but HBV DNA and HBsAg negative are eligible and will undergo monthly monitoring
b. Patients who received intravenous immunoglobulin [IVIG] may have false-positive HBcAb; if HBV DNA and HBsAg are negative, prophylaxis may be omitted but monitoring is required
Active hepatitis C, defined by detectable hepatitis C RNA in plasma by polymerase chain reaction (PCR). Patients with resolved infection may participate if hepatitis C RNA is undetectable.
Received a live, attenuated vaccine within 28 days prior to initiation of trial treatment.
a. Patients must not receive live vaccines while receiving trial intervention and for at least 6 months after the last dose of surovatamig or rituximab, and until B-cell recovery is confirmed.
Active tuberculosis (TB) or history of completed treatment for active TB within the past 12 months.
a. Interferon-gamma release assay (IGRA) testing must be performed if TB is suspected.
History of other prior malignancies, except defined low-risk cases.
Current autoimmune disease requiring immunosuppressive therapy other than prednisolone less than 20 mg daily (or equivalent).
Current seizure disorder requiring therapy (patients with history must have complete CNS workup).
History of clinically significant medical or psychiatric conditions interfering with trial participation or safety.
Participation in another clinical trial with an investigational product within the last 28 days or 5 half-lives.
Female patient who is pregnant, breastfeeding, or planning pregnancy or egg donation during or 12 months after treatment.
Male patients planning to father a child or donate sperm during or 12 months after treatment.

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Interventions

The intervention is Surovatamig. Surovatamig is supplied as a concentrate for solution for intravenous administration (2mg/mL). Arm A (Investigational arm): Surovatamig (cycle 1 is a 14 day cycle

The intervention is Surovatamig. Surovatamig is supplied as a concentrate for solution for intravenous administration (2mg/mL). Arm A (Investigational arm): Surovatamig (cycle 1 is a 14 day cycle including a triple step-up dosing, cycle 2-4 are 28 day cycles with a dose administered every 2 weeks. no radiotherapy). 1. -Day 1 of cycle 1: 0.09 mg, -Day 4 of cycle 1: 0.27 mg -Day 8 of cycle 1: 1.0 mg. 2. Cycles 2-4 (28-day cycle): Surovatamig treatment doses administered on days 1 and 15 of each cycle at 7.2mg. 3. At the end of cycle 4, patients will enter the post-treatment period. All treatment will be administered by the study team (i.e., registered nurse, the lead physician, physicians listed on the trial to assist the lead physician). Drug accountability will be performed by the administering institutions to assess compliance through pharmacy dispensing logs, dose administration records, and verifying patient diaries.