Untreated Follicular Lymphoma
Conditions
Keywords
Follicular Lymphoma
Brief summary
This is a global, randomised, Phase III, multicentre, open-label study evaluating the efficacy, safety and the degree of added benefit of the Surovatamig (AZD0486) plus rituximab combination compared to Investigator's choice of 3 standard immunochemotherapy regimen, conducted in participants with untreated FL.
Detailed description
The study consists of 2 sequential parts. 1. Safety Run-in - this part will compare dose levels of Surovatamig (AZD0486) in combination with rituximab in order to establish the RP3D. 2. Phase III - The Phase III part will assess the superiority of Surovatamig (AZD0486) at RP3D in combination with rituximab, compared to Investigator's choice between 3 standard chemoimmunotherapy regimens. Phase 3 consists of 3 arms 1. Arm A: treatment with Surovatamig plus rituximab Schedule A 2. Arm B: treatment with Surovatamig plus rituximab Schedule B 3. Arm C (Comparator arm): one of the following standard regimens per Investigator's choice: R-CVP + rituximab maintenance, R-CHOP + rituximab maintenance or B-R + rituximab maintenance
Interventions
DRUGSurovatamig
a fully human bispecific monoclonal IgG4 antibody
DRUGR-CHOP
Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone
DRUGR-CVP
Rituximab, Cyclophosphamide, Vincristine and Prednisone
DRUGBR
Bendamustine, Rituximab
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
1. Participant must be at least 18 years of age, inclusive, at the time of signing the ICF. 2. Histologically confirmed diagnosis of classic FL per WHO 2022 classification 3. ECOG performance status of 0 to 2 4. No prior systemic lymphoma-directed therapy 5. Need for systemic treatment meeting at least 1 GELF criteria 6. FDG-avid and measurable disease 7. Stage II to IV and FLIPI 2-5 \[Phase III only\] 8. Adequate liver, hematological, renal and cardiac function. The above is a summary, other inclusion criteria details may apply
Exclusion criteria
1. Follicular large B-cell lymphoma (WHO 2022 classification), formerly Follicular lymphoma Grade 3B (WHO 2016 classification) or suspicion for histologic transformation to high-grade/aggressive lymphoma 2. Contra-indication to BR, RCVP, and R-CHOP 3. Participants with or history of CNS lymphoma 4. History of a clinically relevant CNS medical condition or pathology that required treatment in the preceding year, is currently symptomatic or that which the treating investigator considers to have the potential to interfere with the evaluation of safety 5. Presence of \>5000 circulating lymphoma cells 6. Active or uncontrolled infection (including EBV) requiring systemic therapy and which places participant at unacceptable risk if he/she were to participate in the study. If a participant has a history of COVID-19 within 1 month of C1D1 or contracts COVID while on study treatment, participant must have 2 consecutive negative tests (PCR testing is preferable) performed at least 48 hours apart prior to resuming dosing. All symptoms related to COVID-19 infection should have fully resolved before initiating or resuming treatment 7. Known history of hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) The above is a summary, other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SRI Primary: Determination of the recommended Phase III dose (RP3D) | Up to 1 year | The RP3D will be the dose of Surovatamig selected for the Phase 3 part based on safety data compiled during the safety run-in part |
| Phase 3 Dual Primary: To demonstrate the superiority of Surovatamig plus rituximab compared to Investigator's choice of SoC chemoimmunotherapy | Up to 10 years | PFS, based on Lugano 2014 Response Criteria, as assessed by BICR. |
| SRI Primary: Incidence, nature and severity of AEs and SAEs. Incidence and nature of study drug discontinuations, dose reductions, and dose delays due to AEs | Up to 10 years | Frequency, severity, and relationship to study drug of AEs and SAEs; dose modifications; changes in physical examination and safety procedures. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety Run In and Phase 3: CR Rate | Up to 10 years | CR rate is defined as the proportion of participants achieving a CR at any time as based on Lugano 2014 Response Criteria |
| Safety Run In and Phase 3: CR at EoI | Up to 10 years | Proportion of participants achieving CR at End of Induction based on Lugano 2014 Response Criteria |
| Safety Run In and Phase 3: DoR | up to 10 years | DoR will be defined from the time of first response until progression based on Lugano 2014 criteria, or death due to any cause |
| Safety Run In and Phase 3: PFS (Investigator assessed) | Up to 10 years | PFS (Investigator assessed) is defined as time from randomization until disease progression based on Lugano 2014 Response Criteria or death due to any cause |
| Phase 3: Time to First Subsequent Therapy or Death (TFST) | Up to 10 Years | TFST will be defined as the time from randomization until the start date of first subsequent anti-lymphoma therapy or death due to any cause |
| Safety Run In and Phase 3: OS | Up to 10 years | OS is defined as time until the date of death |
| Phase 3: Time from randomisation to second progression or death (PFS2) | Up to 10 Years | PFS2 will be defined as the time from randomization until the earliest of the progression event, after first subsequent therapy, or death due to any cause |
| Phase 3: CR rate at 30 months (CR30) | Up to 30 months | Proportion of participants in CR rate at 30 months (CR30) based on Lugano 2014 Response Criteria |
| Safety Run in and Phase 3: ORR at EoI (Investigator assessed) | Up to 10 years | ORR defined as the proportion of participants achieving either a PR or CR at End of Induction based on Lugano 2014 Response Criteria |
Countries
Australia, Belgium, Brazil, Canada, China, Finland, Hong Kong, Hungary, India, Japan, Poland, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
PRINCIPAL_INVESTIGATORChan Cheah, MBBS FRACP FRCPA DMSc
Sir Charles Gairdner Hospital (SCGH)
Outcome results
None listed