A Randomised Phase 3 Study Comparing a New Drug (Surovatamig) With Standard Radiotherapy With or Without Rituximab in Adults With Limited Stage Nodal Follicular Lymphoma

NCT07736950 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: NHL45ACTRN12626000311358
• Study Type: interventional
• Target: 138
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to learn if surovatamig works better than standard of care involved-site radiotherapy (ISRT) with or without rituximab to treat patients with limited-stage follicular lymphoma. It will also learn about the safety of the drug. The main questions it aims to answer is whether surovatamig can produce deeper and more durable responses, reduce the risk of disease relapse, and improve event-free survival. Participants will: 1\) Take surovatamig for 4 cycles. The first cycle will have a dose ramp up in 3 steps over a period of 14 days. Cycle 2-4 are for 28 days with drug administered every fortnight. OR 2a) Undergo radiotherapy only for 3 weeks OR 2b) Radiotherapy + rituximab weekly for 6 doses (6 weeks) Visit the clinic once every cycle, at the end of treatment, and be monitored every 3 months in year 1, every 6 months in year 2, and once a year from year 3-5 for checkups and tests.

Conditions

Follicular Lymphoma

Outcome Measures

Primary Outcomes (2)

• Event Free Survival

  Determined by Lugano 2014 Response Criteria and audit of medical records

  Time from date of randomisation until disease progression until end of 5 year follow up.

• Event Free Survival

  As determined by the Lugano 2014 Response Criteria and audit of medical records

  Time from date of randomisation to death from any cause, initiation of new anti-lymphoma treatment or disease progression until end of 10 year follow up. Assessment will be performed at end of treatment, every 3 months in year 1, every 6 months in year 2

Study Arms (3)

Arm A (Investigational arm): Surovatamig

ACTIVE COMPARATOR

This arm involves treatment with Surovatamig only with no radiotherapy. Treatment is in 3 phases. 1. Cycle 1 is a 14 day cycle including a triple step-up dosing: 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. Cycle 2-4 are 28 day cycles with a dose administered every 2 weeks: 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.

Drug: Surovatamig

Arm B1: Involved-Site Radiotherapy (ISRT) 24Gy

NO INTERVENTION

This arm is the standard of care (SOC): Involved-Site Radiotherapy (ISRT) at 24Gy and involves radiotherapy for 3 weeks.

Arm B2: Involved-Site Radiotherapy (ISRT) 24Gy + rituximab x 6 cycles

NO INTERVENTION

This arm is another standard of care (SOC): Involved-Site Radiotherapy (ISRT) at 24Gy with 6 doses of rituximab administered weekly by intravenous (IV) at 375 mg/m\^2. 1 week = 1 cycle.

Interventions

Surovatamig DRUG

Surovatamig is supplied as a concentrate for solution for intravenous administration (2mg/mL).

Arm A (Investigational arm): Surovatamig

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 positron emission tomography/computed tomography (PET/CT) scan demonstrating PET-positive lesion(s), and
• 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:
• Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) less or equal to 3.0 × upper limit of normal (ULN)
• 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
• Estimated creatinine clearance (CrCl) greater or equal to 45 mL/min (as calculated by the Cockcroft-Gault formula)

You may not qualify if:

• 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:
• Myocardial infarction within less or equal to 12 weeks or stroke within 6 months prior to randomisation
• Screening 12-lead electrocardiogram (ECG) showing a baseline QT interval as corrected by Frederica's formula (QTcF) over 480 msec
• 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:
• Patients on effective antiretroviral therapy with undetectable viral load within 6 months prior to trial entry are eligible
• HIV ribonucleic acid (RNA) will be monitored during the trial as clinically indicated

Sponsors & Collaborators

• Australasian Leukaemia and Lymphoma Group: lead

MeSH Terms

Conditions

Lymphoma, Follicular

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Chan Cheah

  Sir Charles Gairdner Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2026
• First Posted: July 30, 2026
• Study Start (Estimated): January 12, 2027
• Primary Completion (Estimated): January 13, 2035
• Study Completion (Estimated): January 13, 2035
• Last Updated: July 30, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share