A Study to Compare the Efficacy and Safety of Golcadomide in Combination With Rituximab (Golca + R) vs Investigator's Choice in Participants With Relapsed/Refractory Follicular Lymphoma Who Have Received at Least 1 Prior Line of Systemic Therapy (GOLSEEK-4)

Official title

A Phase 3, Multicenter, Randomized, Open Label Study to Compare the Efficacy and Safety of Golcadomide in Combination With Rituximab (Golca + R) Vs Investigator's Choice in Participants With Relapsed/Refractory Follicular Lymphoma Who Have Received at Least 1 Prior Line of Systemic Therapy

Overview

The study is designed as a multicenter, randomized, open label Phase 3 study to compare the efficacy and safety of golcadomide in combination with rituximab vs investigator's choice in participants with relapsed/refractory follicular lymphoma who have received at least one line of prior systemic therapy.

Interventions

• Drug Golcadomide
  Specified dose on specified days
• Drug Rituximab
  Specified dose on specified days
• Drug Lenalidomide
  Specified dose on specified days
• Drug Cyclophosphamide
  Specified dose on specified days
• Drug Doxorubicin
  Specified dose on specified days
• Drug Vincristine
  Specified dose on specified days
• Drug Prednisone/Prednisolone
  Specified dose on specified days
• Drug Bendamustine
  Specified dose on specified days

Primary outcome measures

• Progression free survival (PFS) assessed by Independent Review Adjudication committee (IRAC) [Time frame: Up to approximately 32 Months]

Secondary outcome measures (12)

• Overall response rate (ORR) assessed by IRAC [Time frame: Up to approximately 32 Months]
• Overall survival (OS) [Time frame: Up to approximately 83 Months]
• PFS as assessed by investigator [Time frame: Up to approximately 32 Months]
• ORR as assessed by investigator [Time frame: Up to approximately 32 Months]
• Number of participants who achieve complete metabolic response (CMR) [Time frame: Up to approximately 32 Months]
• Duration of Response (DoR) [Time frame: Up to approximately 32 Months]
• Event free survival (EFS) [Time frame: Up to approximately 32 Months]
• Time to next anti-lymphoma treatment (TTNT) [Time frame: Up to approximately 32 Months]
• PFS on next anti-lymphoma treatment (PFS2) [Time frame: Up to approximately 32 Months]
• Time from randomization to meaningful improvement in primary domains of interest in the European Organization for Research and Treatment of Cancer - Quality of Life C30 (EORTC QLQ-C30) Questionnaire [Time frame: Up to approximately 32 Months]
• Time from randomization to meaningful improvement in primary domains of interest in the European Organization for Research and Treatment of Cancer - Non- Hodgkin Lymphoma- Low Grade- 20 items (EORTC QLQNHL- LG20) Questionnaire [Time frame: Up to approximately 32 Months]
• Minimal residual disease (MRD) negativity [Time frame: Up to approximately 32 Months]

Eligibility criteria

Inclusion criteria

\- Participant has histologically confirmed FL (Grade 1, 2, 3a or classic FL) as assessed by local pathology. Adequate fresh tumor biopsy tissue or archived tumor biopsy from the latest relapse if available with corresponding pathology report for retrospective central pathology confirmation of relapse, is required. Evaluation from fine needle aspirate is not permitted.

\- Relapsed or refractory disease: i) Relapsed FL is defined as relapse after an initial response of CR or PR to the most recent prior therapy.

ii) Refractory FL is defined as best response of SD or PD or a response that lasted less than 6 months to the most recent prior therapy.

• Eastern Cooperative Oncology Group (ECOG) 0-2 (ECOG 3 authorized if it is due to lymphoma and not comorbidities).
• Participant must have positron emission tomography (PET)-positive disease with at least one PET-positive lesion and measurable disease on cross section imaging by CT, as defined by Lugano classification.
• Participants with an indication for anti-lymphoma treatment as per investigator assessment based on modified Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria.
• Participant has received at least 1 or more prior lines of systemic therapy with one line consisting of a combination including an anti-CD20 monoclonal antibody (eg, rituximab, obinutuzumab) and an alkylating agent (eg, cyclophosphamide, bendamustine). Prior treatment with radiation therapy does not count as a line of therapy for eligibility.
• Lab parameters:

i) Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 (1.0 x 109 /L), ii) PLT count ≥ 75,000 cells/mm3 (75 x 109 /L) iii) Hb ≥ 7.5 g/dL

• estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73m².
• Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤ 2.5 x upper limit of normal (ULN). In case of documented liver involvement by lymphoma, ALT/SGPT and AST/SGOT must be ≤ 5.0× ULN.
• Serum total bilirubin ≤ 1.5 × ULN (corresponding to mild dysfunction as per National Cancer Institute Organ Dysfunction Working Group \[NCI ODWG\] criteria). In case of documented liver involvement by lymphoma, serum total bilirubin must be ≤ 3.0 × ULN (corresponding to moderate dysfunction as per NCI ODWG criteria). For cases of Gilberts syndrome, serum total bilirubin≤ 5.0 × ULN.
• Adequate cardiac function for participants receiving anthracycline-based chemotherapy, defined as left ventricular ejection fraction (LVEF) ≥ 45% as assessed by echocardiogram (ECHO) as standard of care or multi-gated acquisition scan (MUGA).

Exclusion criteria

• Evidence or history of composite Diffuse large B-cell lymphoma (DLBCL) and FL or of transformed Non-Hodgkin Lymphoma (NHL), including history of prior large B-cell lymphomas (LBCL), or any other indolent lymphoma.
• Follicular large cell as per 5th World Health Organization (WHO) sub-classification (grade 3b FL per WHO 4th classification) or duodenal-type FL.
• Participant has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the participant from compliantly participating in the study based on Investigator's judgment.
• Participant has any condition that confounds the ability to interpret data from the study based on Investigator's or Sponsor's judgment.
• Presence or history of central nervous system (CNS) involvement by lymphoma.
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
• Deep venous thrombosis/Pulmonary embolism within 1 month prior to enrollment.
• Participants with a history of progressive multifocal leukoencephalopathy.
• Participant has any other subtype of lymphoma.
• Participant has persistent diarrhea or malabsorption ≥ Grade 2 (NCI CTCAE v5.0), despite medical management.
• History of another primary malignancy that has not been in remission for ≥ 3 years except for non-invasive malignancies.
• Other protocol-defined Inclusion/Exclusion criteria apply.

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

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 31 centers

• Local Institution - 0225 — Birmingham
• Infirmary Cancer Care — Mobile
• Alaska Oncology and Hematology — Anchorage
• Local Institution - 0215 — Little Rock
• City of Hope Comprehensive Cancer Center — Duarte
• UCSF Helen Diller Medical Center at Parnassus Heights — San Francisco
• Local Institution - 0008 — Jacksonville
• Local Institution - 0214 — Tampa
• … and 23 more centers

China · 23 centers

• Local Institution - 0246 — Beijing
• Beijing Cancer hospital — Beijing
• Local Institution - 0172 — Fuzhou Fujian
• Sun Yat-sen University Cancer Center — Guangzhou
• Local Institution - 0241 — Harbin
• Union Hospital Tongji Medical College Huazhong University of Science and Technology — Wuhan
• Local Institution - 0175 — Changsha
• Inner Mongolia Cancer Hospital — Hohhot
• … and 15 more centers

Germany · 14 centers

Center list to be confirmed — check the primary protocol.

Japan · 10 centers

Center list to be confirmed — check the primary protocol.

France · 8 centers

• CHU Bordeaux Haut-Leveque — Pessac
• … and 7 more centers

Australia · 7 centers

• Westmead Hospital — Westmead
• Local Institution - 0132 — Adelaide
• Local Institution - 0131 — Hobart
• Local Institution - 0128 — Heidelberg
• Cabrini Hospital - Malvern — Malvern
• Local Institution - 0127 — Perth
• Local Institution - 0224 — Perth

Brazil · 7 centers

• Local Institution - 0159 — Vitória
• Local Institution - 0088 — Niterói
• Local Institution - 0087 — Porto Alegre
• Local Institution - 0079 — São Paulo
• Local Institution - 0089 — Rio de Janeiro
• Local Institution - 0066 — São Paulo
• Local Institution - 0092 — São Paulo

Italy · 7 centers

Center list to be confirmed — check the primary protocol.

Greece · 6 centers

Center list to be confirmed — check the primary protocol.

Spain · 6 centers

Center list to be confirmed — check the primary protocol.

Canada · 5 centers

• Local Institution - 0200 — Victoria
• Princess Margaret Cancer Centre — Toronto
• Local Institution - 0250 — Québec
• Local Institution - 0192 — Sherbrooke
• Local Institution - 0226 — Sherbrooke

India · 5 centers

Center list to be confirmed — check the primary protocol.

Poland · 5 centers

Center list to be confirmed — check the primary protocol.

South Korea · 4 centers

Center list to be confirmed — check the primary protocol.

Turkey (Türkiye) · 4 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 4 centers

Center list to be confirmed — check the primary protocol.

Chile · 3 centers

• Local Institution - 0154 — Santiago
• Local Institution - 0155 — Santiago
• Local Institution - 0153 — Santiago

Finland · 3 centers

• Local Institution - 0151 — Oulu
• Local Institution - 0152 — Turku
• Local Institution - 0150 — Helsinki

Netherlands · 3 centers

Center list to be confirmed — check the primary protocol.

Saudi Arabia · 3 centers

Center list to be confirmed — check the primary protocol.

United Arab Emirates · 2 centers

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06911502 · CA073-1003 · 2024-519152-82 · U1111-1314-3909

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗