Golcadomide, Poseltinib, and Rituximab for Relapsed/Refractory Diffuse Large B-cell Lymphoma

NCT07269639 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: H-2507-184-1662
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is a proof-of-concept, pilot study, phase I/II clinical trial aimed at generating preliminary data on the combination of golcadomide, poseltinib, and rituximab.

Conditions

Large B-Cell Lymphoma (LBCL)

Keywords

large b-cell lymphoma; golcadomide; poseltinib; rituximab

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  The primary endpoint was the Overall response rate, defined as the proportion of participants who achieved either CMR or PMR according to the Lugano criteria 2014. The primary analysis will be conducted in the efficacy evaluable population. A one-sample exact binomial test (one-sided, α=0.05) will be used to compare the observed ORR against the null hypothesis value of 30%. If the lower bound of the exact one-sided 95% CI for the observed ORR exceeds 30%, the null hypothesis will be rejected, suggesting that the combination therapy demonstrates meaningful efficacy.

  The evaluation time frame is from baseline up to 18 months.

Secondary Outcomes (6)

• Progression-free survival (PFS)

  The evaluation time frame extends from baseline to 1 year and 3 year after the last patient in.

• Overall survival (OS)

  The evaluation time frame extends from baseline to 3 years after the last patient in.

• Complete metabolic response (CMR) rate

  The evaluation time frame is from baseline up to 18 months.

• Duration of response (DOR)

  The evaluation time frame extends from baseline to 1 year and 3 years after the last patient in.

• Recommended poseltinib dose

  through study part 1 completion, up to 8 weeks.

Study Arms (1)

Treatment arm

EXPERIMENTAL

golcadomide + poseltinib + rituximab (GoPro)

Drug: Golcadomide + Poseltinib + Rituximab

Interventions

Golcadomide + Poseltinib + Rituximab DRUG

Participants will receive 0.4 mg of golcadomide once daily for 14 consecutive days for 18 cycles in 28-day cycles. The first 6 cycles will be administered in combination with rituximab and poseltinib, while the remaining 12 cycles will be conducted with poseltinib alone. During the maintenance period (Cycles 7-18), the first day of study treatment administration with golcadomide is designated as Day 1 of each cycle. Rituximab can be administered with or up to 2 hours after the morning dose of golcadomide in the fed or fasted state. For Cycles 1-6, the first day of study treatment administration with rituximab is designated as Day 1 of each cycle. Rituximab will be administered as an IV infusion at a dose of 375 mg/m2 on Days 1, 8, 15, and 22 of Cycle 1, and Day 1 of Cycles 2-6. Poseltinib is administered orally twice daily, approximately every 12 hour. Part 1 (safety cohort) of the study will be conducted in up to approximately 9 participants to select the optimal RP2D of poseltinib.

Treatment arm

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must satisfy the following criteria to be enrolled in the study
• Subject is ≥ 19 years of age at the time of signing the informed consent form (CRF).
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• Subject has histologically confirmed (per local evaluation) diagnosis of aggressive large B-cell lymphoma according to 2022 WHO classification, specifically:
• A. DLBCL, NOS (including GCB and ABC types) B. DLBCL/high grade B-cell lymphoma, with MYC and BCL2 rearrangements C. High grade B-cell lymphoma, NOS D. T-cell/histiocyte-rich large B-cell lymphoma E. EBV-positive DLBCL
• Relapsed or refractory disease following at least 1 prior line of therapy (must include an anthracycline-based treatment), and ineligible for hematopoietic stem cell transplantation.
• Subjects must have measurable disease defined by at least one fluorodeoxyglucose (FDG)-avid lesion for FDG-avid subtype and one bi-dimensionally measurable (\> 1.5 cm in longer diameter) disease by computed tomography (CT) or magnetic resonance imaging (MRI), as defined by the Lugano classification.
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Subject must have the following laboratory values:
• A. ANC ≥ 1.0 × 109/L or ≥ 0.5 × 109/L in case of documented bone marrow involvement of DLBCL-related hypersplenism present. It is not permissible to administer G-CSF to achieve minimum ANC levels within 7 days prior to screening complete blood count (or within 14 days prior for pegfilgrastim).
• B. Hemoglobin ≥ 75 g/L (7.5 g/dL). Transfusion is permitted in cases of bone marrow involvement of lymphoma, and screening will be conducted at least one week after transfusion.
• C. Platelets ≥ 75 × 109/L or ≥ 50 × 109/L in case of documented bone marrow involvement of DLBCL-related hypersplenism present, without transfusion for 7 days.
• D. AST and ALT ≤ 2.5 × ULN. In case of documented liver involvement by lymphoma, AST and ALT must be ≤ 5.0 × ULN.
• E. 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.

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment:
• Subject who has had prior treatment with golcadomide.
• Subject who has had prior treatment with BTK inhibitor.
• Subject has life expectancy ≤ 2 months.
• Subject has received any of the following:
• A. Major surgery (as defined by the Investigator) within 28 days of initiating study treatment. Subjects must have recovered from any clinically significant effects of recent surgery.
• B. Radiation therapy within 28 days prior to initiating study treatment. C. Use of any systemic anti-cancer treatment (approved or investigational) within 28 days or 5 half-lives prior to starting study treatment, whichever is shorter. (Participation in another interventional clinical trial concurrent with this study is not permitted, except for those who have completed treatment with the prior investigational agent(s) and are currently in long-term follow up)
• Subject has previously received solid organ transplantation.
• Subject has undergone allogeneic SCT within 1 year prior to initiating study treatment or autologous SCT within 3 months prior to initiating study treatment.
• A. Subject who had received prior SCT should not have any Grade \>1 treatment-related toxicity.
• B. Subject who had received prior SCT should not have clinically significant, active graft-versus-host disease (GVHD).
• Subject has any other subtype of lymphoma. Cases of primary mediastinal (thymic) large B-cell lymphoma, primary cutaneous DLBCL-leg type, Grade 3b FL, ALK-positive large B-cell lymphoma, primary effusion lymphoma, or Burkitt lymphoma are excluded.
• Subject has active central nervous system (CNS) involvement by lymphoma
• Subject has any significant medical condition (e.g., uncontrolled diabetes mellitus, uncontrolled hypertension), including active or uncontrolled infection, presence of laboratory abnormality, or psychiatric illness that places the subject at an unacceptable risk for treatment-related complications, if he/she were to participate in the study.
• Subject has any condition that confounds the ability to interpret data from the study.

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (1)

Seoul National University Hospital

Seoul, 03080, South Korea

Location

MeSH Terms

Interventions

poseltinib; Rituximab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Ja Min Byun, MD, PhD

CONTACT

+82-2-2072-7217; jaminbyun@snu.ac.kr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D. Ph.D.

Study Record Dates

• First Submitted: November 25, 2025
• First Posted: December 8, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: December 8, 2025

Record last verified: 2025-11

Locations

KR (1)