Pola-R-CHP Plus Sonrotoclax in Untreated BCL2-High/Double-Hit LBCL

NCT07638787 | Not Yet Recruiting Phase 1

• 1 other identifier: SONATA
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I/II study. The Phase I part will evaluate the safety and tolerability of sonrotoclax in combination with polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP), using a standard 3+3 dose-escalation design, to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D). The Phase II part will assess the efficacy of the combination regimen in patients with previously untreated LBCL with high BCL2 expression or MYC/BCL2 rearrangements.

Conditions

Large B-cell Lymphoma

Keywords

LBCL; BCL2; DHL; Sonrotoclax

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD) of sonrotoclax in combination with Pola-R-CHP

  The MTD is defined as the highest dose at which the incidence of dose-limiting toxicity (DLT) is less than 1/3 of patients.

  From first dose through 21 consecutive calendar days after reaching the target dose (up to 26 days)

• Recommended Phase II Dose (RP2D)

  The determined Maximum Tolerated Dose (MTD) and its dosing regimen will serve as the recommended Phase II dose (RP2D) for the combination regimen, unless safety data support the use of a lower dose.

  At completion of the DLT evaluation period, up to 26 days

• Complete response rate

  CR rate at the end of treatment by FDG-PET defined as the proportion of participants with CR at the end of treatment according to the 2014 Lugano Response Criteria; as determined by the investigator and IRC (separately)

  End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]

Secondary Outcomes (5)

• Objective response rate

  End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]

• Progression-free survival

  From enrollment to the first occurrence of disease progression or relapse, or death from any cause, whichever occurs earlier (up to 24 months)

• Overall survival

  up to approximately 3 years

• Duration of Response

  From enrollment to the first occurrence of disease progression or relapse, or death from any cause, whichever occurs earlier (up to 24 months)

• Safety and Tolerability

  From enrollment to study completion, a maximum of 3 years

Study Arms (1)

Sonrotoclax + Pola-R-CHP

EXPERIMENTAL

Eligible participants will receive sonrotoclax plus Pola-R-CHP. In Phase I, three dose levels of sonrotoclax will be evaluated with a ramp-up schedule in Cycle 1 (Days 4-10), followed by Days 1-10 dosing at the assigned dose in subsequent cycles: 320 mg, 480 mg, and 640 mg QD. Dose escalation uses a standard 3+3 design to determine the MTD of sonrotoclax. The RP2D will be used with Pola-R-CHP in Phase II.

Drug: Polatuzumab Vedotin; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Sonrotoclax

Interventions

Polatuzumab Vedotin DRUG

Polatuzumab vedotin IV infusion will be administered as per the schedule specified in the respective arm

Sonrotoclax + Pola-R-CHP

Rituximab DRUG

Rituximab IV infusion will be administered as per the schedule specified in the respective arm.

Sonrotoclax + Pola-R-CHP

Cyclophosphamide DRUG

Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.

Sonrotoclax + Pola-R-CHP

Doxorubicin DRUG

Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.

Sonrotoclax + Pola-R-CHP

Prednisone DRUG

Prednisone PO will be administered as per the schedule specified in the respective arm.

Sonrotoclax + Pola-R-CHP

Sonrotoclax DRUG

Sonrotoclax PO will be administered as per the schedule specified in the respective arm.

Sonrotoclax + Pola-R-CHP

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with newly diagnosed large B-cell lymphoma confirmed by histopathology, CD20-positive, excluding central nervous system lymphoma;
• Patients aged 18 to 75 years;
• International Prognostic Index score of 2 to 5;
• Patients with high BCL-2 expression or double-hit lymphoma characteristics;
• No prior anti-tumor treatment of any type;
• Estimated survival time ≥ 6 months;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2;
• Measurable lesions confirmed by radiological examination, defined as: at least one lymph node lesion with the longest diameter \> 1.5 cm, or at least one extranodal lesion with the longest diameter \> 1.0 cm, and at least two accurately measurable perpendicular diameters;
• Patients or their legal representatives must provide written informed consent before conducting any study-specific examinations or procedures;
• No prior treatment for lymphoma (except glucocorticoids).

You may not qualify if:

• Prior solid organ transplantation or stem cell transplantation;
• Complicated with uncontrolled coagulation disorders, connective tissue diseases, severe infectious diseases, etc.;
• Suspected active or latent tuberculosis (confirmed by a positive interferon-gamma release assay);
• Any of the following abnormal laboratory test values (unless these abnormalities are all caused by the underlying lymphoma):
• Neutrophils \< 1.0×10⁹/L;
• Platelets \< 75×10⁹/L;
• Serum AST and ALT ≥ 2.5× upper limit of normal (ULN);
• Total bilirubin ≥ 1.5×ULN;
• Serum creatinine clearance \< 30 mL/min (calculated using the Cockcroft-Gault formula);
• Uncontrolled or significant cardiovascular diseases, including but not limited to:
• Left ventricular ejection fraction (LVEF) \< 50%;
• Primary cardiomyopathy, such as dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, etc.;
• Clinically significant QTc prolongation, with QTc interval \> 470 ms (females) or 480 ms (males), second-degree type II atrioventricular block, or third-degree atrioventricular block;
• Current or past history of central nervous system (CNS) diseases, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative diseases. However, participants with a history of stroke who have not had a stroke or transient ischemic attack in the past 2 years and have no residual neurological deficits as judged by the investigator are allowed to participate in the study;
• Patients with mental illness or other patients known or suspected to be unable to fully comply with the study protocol;

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital, Shanghai JiaoTong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

MeSH Terms

Interventions

polatuzumab vedotin; Rituximab; Cyclophosphamide; Doxorubicin; Prednisone

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Central Study Contacts

Peng-Peng Xu

CONTACT

+862164370045; pengpeng_xu@126.com

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: Professor and Chief Physician

Study Record Dates

• First Submitted: May 28, 2026
• First Posted: June 10, 2026
• Study Start: June 15, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): April 30, 2029
• Last Updated: June 10, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)