A Study to Evaluate the Safety and Efficacy of Polatuzumab Vedotin in Combination With Rituximab, Gemcitabine and Oxaliplatin Compared to Rituximab, Gemcitabine and Oxaliplatin Alone in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (POLARGO)

A Phase III, Open-Label, Multicenter, Randomized, Study Evaluating the Safety and Efficacy of Polatuzumab Vedotin in Combination With Rituximab Plus Gemcitabine Plus Oxaliplatin (R-GEMOX) Versus R-GEMOX Alone in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

This study is a multicenter, open-label study of polatuzumab vedotin administered by intravenous (IV) infusion in combination with rituximab, gemcitabine and oxaliplatin (R-GemOx) in participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The study comprises of two stages: a safety run-in stage and a randomized controlled trial (RCT).

Study Overview

• Status: Completed
• Conditions: Diffuse Large B-Cell Lymphoma
• Intervention / Treatment: Drug: Polatuzumab Vedotin; Drug: Rituximab; Drug: Gemcitabine; Drug: Oxaliplatin

Detailed Description

The safety run-in stage (Stage 1) will assess the safety of polatuzumab vedotin plus rituximab, gemcitabine and oxaliplatin (Pola-R-GemOx) in 10 participants. The randomized controlled trial (RCT) (Stage 2) will compare Pola-R-GemOx versus R-GemOx alone using overall survival (OS). This is an event-driven trial.

• Study Type: Interventional
• Enrollment (Actual): 270
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 41253-190
      • Hospital Sao Rafael - HSR
  • Rio Grande do Norte
    • Natal, Rio Grande do Norte, Brazil, 59040150
      • Liga Norte Riograndense Contra O Cancer
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, DUMMY_VALUE
      • Hospital das Clinicas - UFRGS
  • São Paulo
    • São Paulo, São Paulo, Brazil, 05403-000
      • Hospital das Clinicas - FMUSP
• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre
    • St. Catharines, Ontario, Canada, L2R 7C6
      • Niagara Health Systems - St. Catherines General Site
  • Quebec
    • Trois-Rivières, Quebec, Canada, G8Z 3R9
      • Centre Hospitalier Regional de Trois-Rivieres
• China
  • Changsha, China, 410006
    • Hu Nan Provincial Cancer Hospital
  • Chengdu, China, 610047
    • West China Hospital - Sichuan University
  • Guangzhou, China, 510060
    • Cancer Center, Sun Yat-sen University of Medical Sciences
  • Nanchang, China, 330006
    • The 1st Affiliated Hospital of Nanchang Unversity
  • Nanning, China, 530021
    • Guangxi Cancer Hospital of Guangxi Medical University
  • Tianjin, China, 300020
    • Institute of Hematology and Hospital of Blood Disease
  • Wuhan, China, 430023
    • Union Hospital Tongji Medical College Huazhong University of Science and Technology
  • Xi'an, China, 710061
    • First Affiliated Hospital of Medical College of Xi'an Jiaotong University
• Finland
  • Oulu, Finland, 90029
    • Oulu University Hospital
  • Tampere, Finland, 33520
    • Tampere University Hospital
• France
  • Créteil, France, 94010
    • Hôpital Henri Mondor
  • Pessac, France, 33604
    • Hopital De Haut Leveque
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Strasbourg, France, 67200
    • ICANS
  • Tours, France, 37044
    • Hopital Bretonneau
• Germany
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm
• Greece
  • Athens, Greece, 115 27
    • Laiko General Hospital
  • Athens, Greece, 124 62
    • Attiko Hospital
• India
  • Maharashtra
    • Mumbai, Maharashtra, India, 400013
      • Tata Memorial Hospital
  • National Capital Territory of Delhi
    • New Delhi, National Capital Territory of Delhi, India, 110029
      • All India Institute of Medical Sciences ,Institute Rotary Cancer Hospital
  • West Bengal
    • Kolkata, West Bengal, India, 700160
      • Tata Medical Center
• Ireland
  • Dublin, Ireland, DUMMY_VALUE
    • St James' Hospital
• Italy
  • Apulia
    • Bari, Apulia, Italy, 70124
      • Uni Degli Studi Di Bari, Policlinico
  • Emilia-Romagna
    • Modena, Emilia-Romagna, Italy, 41123
      • Azienda Ospedaliero-Universitaria Policlinico di Modena Ematologia
  • Lazio
    • Rome, Lazio, Italy, 00133
      • Az. Osp. Uni Ria Policlinico Tor Vergata
  • Tuscany
    • Prato, Tuscany, Italy, 59100
      • USL 4 di Prato - Nuovo Ospeale di Prato
• Mexico
  • Distrito Federal, Mexico, 14080
    • Instituto Nacional de Cancerologia
  • Mexico CITY (federal District)
    • Mexico City, Mexico CITY (federal District), Mexico, 02990
      • Hospital de Especialidades Centro Medico Nacional La Raza
    • Mexico City, Mexico CITY (federal District), Mexico, 03100
      • Health Pharma Professional Research
• South Korea
  • Busan, South Korea, 49241
    • Pusan National University Hospital
  • Daejeon, South Korea, 35015
    • Chungnam National University Hospital
  • Gyeongsangnam-do, South Korea, 52727
    • Gyeongsang National University Hospital
  • Seongnam-si, South Korea, 13605
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
• Spain
  • Madrid, Spain, 28041
    • Hospital Univ. 12 de Octubre
  • Salamanca, Spain, 37007
    • Hospital Clínico Universitario de Salamanca
  • Valencia, Spain, 46017
    • Hospital Universitario Dr. Peset
  • Barcelona
    • Badalona, Barcelona, Spain, 08915
      • Hospital Universitari Germans Trias i Pujol
  • Tenerife
    • San Cristóbal de La Laguna, Tenerife, Spain, 38320
      • Hospital Universitario de Canarias
• Turkey (Türkiye)
  • Adapazari/Sakarya, Turkey (Türkiye), 54100
    • Sakarya Universitesi Egitim ve Arastirma Hastanesi
  • Ankara, Turkey (Türkiye), 06200
    • Abdurrahman Yurtarslan Onkoloji Training and Research Hospital
  • Antalya, Turkey (Türkiye), 07059
    • Akdeniz Uni School of Medicine
  • Istanbul, Turkey (Türkiye), 34098
    • Istanbul University Cerrahpasa Medical Faculty
  • Istanbul, Turkey (Türkiye), 34093
    • Istanbul Uni Istanbul Medical Faculty
  • Kocaeli, Turkey (Türkiye), 41380
    • Kocaeli Universitesi Tip Fakultesi
  • Ni?anta??, Turkey (Türkiye), 34365
    • Amerikan HAstanesi Onkoloji Birimi Te?vikiye
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham City Hospital
• United States
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Cancer Specialists
    • Pembroke Pines, Florida, United States, 33028
      • Memorial Cancer Institute at Memorial West
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • IHA Hematology Oncology Consultants - Ann Arbor
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • MSKCC at Basking Ridge
    • Montvale, New Jersey, United States, 07645
      • Memorial Sloan Kettering Cancer Center at Bergen
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically-confirmed diffuse large B-cell lymphoma, not otherwise specified (NOS) or history of transformation of indolent disease to DLBCL
• Relapsed disease (disease that has recurred following a response that lasted ≥ 6 months from completion of the last line of therapy) or refractory disease (disease that did not respond to or that progressed during therapy or progressed within 6 months (< 6 months) of prior therapy)
• At least one (≥ 1) line of prior systemic therapy:
• Patients may have undergone autologous hematopoietic stem cell transplantation (HSCT) prior to recruitment; In such cases, salvage chemotherapy (e.g., rituximab, dexamethasone, cytarabine, and cisplatin [R-DHAP] and rituximab, ifosfamide, carboplatin, and etoposide phosphate [R-ICE]) will be counted as one line of therapy and conditioning chemotherapy (e.g., BEAM) followed by consolidative autologous HSCT will be counted as one line of therapy
• Patients may have undergone allogeneic HSCT prior to recruitment, so long as they are off all immunosuppressive therapy and have no active GVHD; In such cases, salvage chemotherapy (e.g., R-DHAP and R-ICE) will be counted as one line of therapy and conditioning chemotherapy (e.g., carmustine, etoposide, cytarabine, and melphalan [BEAM]) followed by allogeneic HSCT will be counted as a separate line of therapy
• Participants may have undergone CAR T-cell therapy prior to recruitment. In such cases, cell collection, conditioning chemotherapy, and infusion will be counted as one line of therapy.
• Local therapies (e.g., radiotherapy) will not be considered as lines of treatment
• For participants with a history of the transformation of indolent disease to DLBCL, it is preferred that participants have received at least one treatment for the transformed lymphoma. However, if there are cases where the participants have received an anthracycline-containing chemotherapy regimen (such as R-CHOP) for the indolent lymphoma only, then these participants can be considered as eligible.
• At least one bi-dimensionally measurable lesion, defined as > 1.5 cm in its longest dimension as measured by CT or MRI
• Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2
• Adequate hematological function
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm,

Exclusion Criteria:

• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
• Contraindication to rituximab, gemcitabine or oxaliplatin
• Peripheral neuropathy assessed to be > Grade 1 according to NCI CTCAE v5.0
• Prior use of polatuzumab vedotin or a gemcitabine plus platinum-based agent combination, recent participation in a clinical trial, and/or treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy within 2 weeks
• Planned autologous or allogenic stem cell transplantation or CAR T-cell therapy at time of recruitment
• Primary or secondary central nervous system (CNS) lymphoma
• Richter's transformation or prior CLL
• Abnormal laboratory values or health conditions, as assessed by the investigator, any known conditions preventing adherence to protocol or active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
• Vaccination with a live vaccine within 4 weeks prior to treatment
• Recent major surgery (within 6 weeks before the start of Cycle 1 Day 1) other than for diagnosis
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 12 months after the last dose of study drug
• Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pola-R-GemOx (Stage 1); Participants will receive polatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) for a maximum dose of 240 mg per cycle (mg/cycle) administered intravenously (IV) and rituximab 375 milligrams per square meter (mg/m^2) administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m^2 administered IV and oxaliplatin 100 mg/m^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.	Drug: Polatuzumab Vedotin; Polatuzumab vedotin 1.8 mg/kg for a maximum dose of 240 mg/cycle IV on Day 1 of each 21-day cycle for up to 8 cycles.; Drug: Rituximab; Rituximab 375 mg/m2 IV on Day 1 of each 21-day cycle for up to 8 cycles.; Other Names: Mabthera; Rituxan; Drug: Gemcitabine; Gemcitabine 1000 mg/m2 IV on Day 2 of each 21-day cycle for up to 8 cycles.; Drug: Oxaliplatin; Oxaliplatin 100 mg/m2 IV on Day 2 of each 21-day cycle for up to 8 cycle.
Experimental: Pola-R-GemOx (Stage 2); Participants will receive polatuzumab vedotin 1.8 mg/kg for a maximum dose of 240 mg/cycle administered IV and rituximab 375 mg/m^2 administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m^2 administered IV and oxaliplatin 100 mg/m^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.	Drug: Polatuzumab Vedotin; Polatuzumab vedotin 1.8 mg/kg for a maximum dose of 240 mg/cycle IV on Day 1 of each 21-day cycle for up to 8 cycles.; Drug: Rituximab; Rituximab 375 mg/m2 IV on Day 1 of each 21-day cycle for up to 8 cycles.; Other Names: Mabthera; Rituxan; Drug: Gemcitabine; Gemcitabine 1000 mg/m2 IV on Day 2 of each 21-day cycle for up to 8 cycles.; Drug: Oxaliplatin; Oxaliplatin 100 mg/m2 IV on Day 2 of each 21-day cycle for up to 8 cycle.
Active Comparator: R-GemOx (Stage 2); Participants will receive rituximab 375 mg/m^2 administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m^2 administered IV and oxaliplatin 100 mg/m^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.	Drug: Rituximab; Rituximab 375 mg/m2 IV on Day 1 of each 21-day cycle for up to 8 cycles.; Other Names: Mabthera; Rituxan; Drug: Gemcitabine; Gemcitabine 1000 mg/m2 IV on Day 2 of each 21-day cycle for up to 8 cycles.; Drug: Oxaliplatin; Oxaliplatin 100 mg/m2 IV on Day 2 of each 21-day cycle for up to 8 cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage 1: Number of Participants With Adverse Events (AEs)	An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	From treatment initiation until 90 days after the last dose of study drug or initiation of non-protocol-specified anti-lymphoma treatment (NALT) (Up to approximately 8.3 months)
Stage 1: Number of Participants With Peripheral Neuropathy (PN)	An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Participants receiving polatuzumab vedotin may develop PN, including peripheral sensory and/or motor neuropathy. Symptoms included hypoesthesia, hyperesthesia, paresthesia, dysesthesia, discomfort, a burning sensation, weakness, gait disturbance, loss of balance, orthostatic hypotension, syncope, or neuropathic pain.	From treatment initiation until 90 days after the last dose of study drug or initiation of NALT (Up to approximately 8.3 months)
Stage 2: Overall Survival (OS)	OS was defined as the time from randomization to the death from any cause during the study. Participants who were not reported as having died at the time of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization. Kaplan-Meier (KM) method was used to estimate median OS for each treatment arm.	From randomization to death (Up to approximately 34 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage 1 and Stage 2: Progression-free Survival (PFS)	PFS=time from randomization to the first occurrence of disease progression (PD) (based on either: PET-CT data/not including any PET data), as determined by investigator, per Lugano response criteria or death due to any cause, whichever occurs first. PD based on PET-CT data=score 4 (uptake moderately > liver) or 5 (uptake markedly higher than liver &/or new lesions) on 5-point scale (5PS) with an increase in intensity of uptake from baseline at individual target nodes/nodal masses and/or new FDG-avid foci extranodal lesions consistent with lymphoma at interim or end-of-treatment assessment. New lesions: New FDG-avid foci consistent with lymphoma rather than another etiology, Bone marrow: New/recurrent FDG-avid foci. Participants who did not report PD nor died at time of analysis were censored on the date of last evaluable tumor assessment if post-baseline tumor assessment or on date of randomization if no post-baseline tumor assessment. KM methodology was used to estimate median PFS.	From randomization to first occurrence of PD or death (Up to approximately 34 months)
Stage 2: Complete Response Rate (CRR), as Determined by an Independent Review Committee (IRC) at the End of Treatment	CRR was defined as the percentage of participants who had a complete metabolic response (CMR) based on positron emission tomography-computed tomography (PET-CT) according to Lugano response criteria at the end of treatment as determined by IRC. CMR was defined as score 1, 2, or 3 (1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake >mediastinum but ≤ liver) with or without a residual mass on 5PS at lymph nodes and extra lymphatic sites. In Waldeyer's ring or extranodal sites with high physiologic uptake or with activation within spleen or marrow (e.g., with chemotherapy/myeloid colony-stimulating factors), uptake may be greater than normal mediastinum and/or liver. In this circumstance, CMR was inferred if uptake at sites of initial involvement was no greater than surrounding normal tissue even if the tissue had high physiologic uptake; no new lesions and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Percentages are rounded off.	Up to approximately 8.5 months
Stage 2: Objective Response Rate (ORR) as Determined by an IRC at End of Treatment	ORR=percentage of participants with CMR/partial metabolic responses (PMR), based on PET-CT per Lugano response criteria as per an IRC. CMR=score 1, 2, or 3 with/ without a residual mass on 5PS at lymph nodes (LN) & extra lymphatic sites. In Waldeyer's ring or extra nodal sites with high physiologic uptake or with activation within spleen/marrow, uptake may be greater than normal mediastinum &/or liver. In this case, CMR was inferred if uptake at sites of initial involvement was no greater than surrounding normal tissue even if the tissue had high physiologic uptake; no new lesions & no evidence of FDG-avid disease in bone marrow. PMR=score 4 or 5 on 5PS (4=uptake moderately > liver; 5=uptake markedly higher than liver &/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size at LN & extra lymphatic sites; no new lesions & residual uptake higher than uptake in normal marrow but reduced compared with baseline. Percentages are rounded off.	Up to approximately 8.5 months
Stage 1 and Stage 2: Percentage of Participants With Best Overall Response (BOR) as Determined by the Investigator	BOR was defined as the best response while on study (based on PET-CT or CT data) according to Lugano response criteria, as determined by the investigator. CMR and PMR based on PET-CT data were defined as outlined in the ORR outcome measure (OM) number 8. CT-based complete radiologic response was defined as target lymphatic nodes/nodal masses regression to ≤ 1.5 centimeters (cm) in longest transverse diameter of a lesion (LDi); no extralymphatic sites of disease; absence of non-measured lesion; enlarged organs regress to normal; no new lesions and bone marrow normal by morphology, if indeterminate, immunohistochemistry (IHC) negative. CT-based partial response was defined as ≥50% decrease in sum of the product of the perpendicular diameters for multiple lesions (SPD) of up to 6 target measurable nodes and extra nodal sites; absent/normal, regressed, but no increase in non-measured lesions; spleen regressed by >50% in length beyond normal and no new lesions. Percentages are rounded off.	Up to approximately 34 months
Stage 1 and Stage 2: CRR as Determined by the Investigator at End of Treatment	CRR was defined as the percentage of participants who had CMR based positron emission tomography-computed tomography (PET-CT) according to Lugano response criteria at the end of treatment as determined by investigator. CMR was defined as score 1, 2, or 3 (1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake >mediastinum but ≤ liver) with or without a residual mass on 5PS at lymph nodes and extra lymphatic sites. In Waldeyer's ring or extranodal sites with high physiologic uptake or with activation within spleen or marrow (e.g., with chemotherapy/myeloid colony-stimulating factors), uptake may be greater than normal mediastinum and/or liver. In this circumstance, CMR was inferred if uptake at sites of initial involvement is no greater than surrounding normal tissue even if the tissue has high physiologic uptake; no new lesions and no evidence of FDG-avid disease in bone marrow. Percentages are rounded off.	Stage 1: Up to approximately 6.2 months and Stage 2: Up to approximately 8.5 months
Stage 1 and Stage 2: ORR as Determined by the Investigator at End of Treatment	ORR=percentage of participants with CMR/PMR, based on PET-CT as determined by investigator per Lugano response criteria. CMR=score 1, 2, or 3 with/ without a residual mass on 5PS at LN & extra lymphatic sites. In Waldeyer's ring or extra nodal sites with high physiologic uptake or with activation within spleen/marrow, uptake may be greater than normal mediastinum &/or liver. In this case, CMR was inferred if uptake at sites of initial involvement was no greater than surrounding normal tissue even if the tissue had high physiologic uptake; no new lesions & no evidence of FDG-avid disease in bone marrow. PMR=score 4 or 5 on 5PS (4=uptake moderately > liver; 5=uptake markedly higher than liver &/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size at LN & extra lymphatic sites; no new lesions & residual uptake higher than uptake in normal marrow but reduced compared with baseline. Percentages are rounded off.	Stage 1: Up to approximately 6.2 months and Stage 2: Up to approximately 8.5 months
Stage 2: Duration of Response (DOR)	DOR=time from the date of the first occurrence of a documented objective response (complete or partial response [CR/PR]) (based on PET-CT or CT data) as determined by the investigator, using Lugano response criteria, until PD (based on either response: including PET-CT data or not including any PET data) or death, whichever occurred first. CMR and PMR based on PET-CT data were defined as outlined in the ORR OM. CT-based complete and partial response were defined as outlined in the BOR OM. PD defined as outlined in the PFS OM.	Up to approximately 34 months
Stage 1 and Stage 2: Event-free Survival (EFSeff)	EFSeff was defined as the time from randomization to first to the earliest occurrence of the following: PD or relapse using Lugano response criteria (based on either response: including PET-CT data or not including any PET data); death due to any cause or initiation of any NALT. PD based on PET-CT data was defined as score 4 or 5 on 5PS with an increase in intensity of uptake from baseline at individual target nodes/nodal masses and/or new FDG-avid foci extranodal lesions consistent with lymphoma at interim or end-of-treatment assessment. New lesions: New FDG-avid foci consistent with lymphoma rather than another etiology, Bone marrow: New or recurrent FDG-avid foci. Participants with no EFSeff events were censored at the time of the last evaluable tumor assessment if post-baseline assessments were available and participants who did not undergo a post-baseline tumor assessment were censored at the time of randomization. KM method was used to estimate median EFS for each treatment arm.	Up to approximately 34 months
Stage 2: Time to Deterioration in Physical Functioning as Measured by the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire, Core 30 (EORTC QLQ-C30)	Time to deterioration was defined as the time from randomization to the first documentation of a 10-point decrease in EORTC QLQ-C30 physical functioning scale. EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), global health status and quality of life (GHS/QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The functioning items were scored on a 4-point scale that ranged from "not at all" to "very much". Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher functioning). KM method was used to estimate median time to deterioration for each treatment arm.	Up to approximately 34 months
Stage 2: Time to Deterioration in Fatigue Scale as Measured by the EORTC QLQ-C30	Time to deterioration was defined as the time from randomization to the first documentation of a 10-point increase from baseline in EORTC QLQ-C30 fatigue scale. EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The symptom scale (fatigue) was scored on a 4-point scale that ranged from "not at all" to "very much". Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher symptom severity). KM method was used to estimate median time to deterioration for each treatment arm.	Up to approximately 34 months
Stage 2: Time to Deterioration in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Lymphoma Subscale (FACT-Lym LymS)	Time to deterioration was defined as the time from randomization to the first documentation of a >3-point decrease from baseline in FACT-Lym LymS. The FACT-Lym subscale has 4 domains: physical well-being, social/family well-being, emotional well-being, functional well-being and lymphoma-specific subscale (LymS). The FACT-Lym LYMS consists of common lymphoma disease and/or treatment-related symptoms (e.g., pain, fever, swelling, night sweats, insomnia, itching, weight loss, fatigue, and loss of appetite). FACT-Lym LYMS contains 15 items scored from 0-4, where 0="Not at all" and 4="very much". Scale score range is from 0 to 60. Higher score indicates better quality of life. KM method was used to estimate the median time to deterioration for each treatment arm.	Up to approximately 34 months
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30	EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The functioning items were scored on a 4-point scale that ranged from "not at all" to "very much". Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher physical functioning).	Baseline, Day 1 of Cycle 2, 3, 5 and 7 (Cycle length= 21 days), end of treatment, long-term follow-up visits every two months (up to approximately 34 months)
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30	EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The symptom scale (fatigue) were scored on a 4-point scale that ranged from "not at all" to "very much". Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher symptom severity). A positive change from baseline indicates an improvement.	Baseline, Day 1 of Cycles 2, 3, 5 and 7 (Cycle length= 21 days), end of treatment, long-term follow-up visits every two months (up to approximately 34 months)
Stage 2: Change From Baseline in FACT-Lym LYMS Scores	The FACT-Lym subscale has 4 domains: physical well-being, social/family well-being, emotional well-being, functional well-being and lymphoma-specific subscale (LymS). The FACT-Lym LYMS consists of common lymphoma disease and/or treatment-related symptoms (e.g., pain, fever, swelling, night sweats, insomnia, itching, weight loss, fatigue, and loss of appetite). FACT-Lym LYMS contains 15 items scored from 0-4, where 0="Not at all" and 4="very much". Scale score range is from 0 to 60. Higher score indicates better quality of life. A positive change from baseline indicates an improvement.	Baseline, Day 1 of Cycle 2, 3, 5 and 7 (Cycle length= 21 days), end of treatment, long-term follow-up visits every two months (up to approximately 34 months)
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores	The FACT/GOG-NTX scale provides a targeted assessment of symptoms of peripheral neuropathy, including sensory, motor, and auditory problems and cold sensitivity. It contains 12 items scored from 0-4, where 0="Not at all" and 4="very much". Scores are summed for a range of 12-44, with lower scores indicating more severe neurotoxicity. Participants completed assessments until progression or non-protocol-specified anti-lymphoma treatment (NALT). Only records on or before the first NALT were summarized.	Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7 and 8 (Cycle length= 21 days), end of treatment, long-term follow-up visits every two months (up to approximately 34 months)
Stage 2: Percentage of Participants With Clinically Meaningful Improvement in EORTC QLQ-C30 Physical Functioning Scale	EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The functioning items were scored on a 4-point scale that ranged from "not at all" to "very much". Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher functioning). Clinically meaningful improvement was defined as a participant with at least a 7 point scale score increase.	Up to approximately 34 months
Stage 2: Percentage of Participants With Clinically Meaningful Improvement in EORTC QLQ-C30 Fatigue Scale	EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The symptom items were scored on a 4-point scale that ranged from "not at all" to "very much". Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher symptom severity). Clinically meaningful improvement was defined as a participant with at least a 9 point scale score decrease.	Up to approximately 34 months
Stage 2: Percentage of Participants With Clinically Meaningful Improvement in FACT-Lym LYMS	The FACT-Lym subscale has 4 domains: physical well-being, social/family well-being, emotional well-being, functional well-being and lymphoma-specific subscale (LymS). The FACT-Lym LYMS consists of common lymphoma disease and/or treatment-related symptoms (e.g., pain, fever, swelling, night sweats, insomnia, itching, weight loss, fatigue, and loss of appetite). FACT-Lym LYMS contains 15 items scored from 0-4, where 0="Not at all" and 4="very much". Scale score range is from 0 to 60. Higher score indicates better quality of life. Clinically meaningful improvement was defined as a 3-point increase from baseline.	Up to approximately 34 months
Stage 2: Number of Participants With AEs	An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	From treatment initiation until 90 days after the last dose of study drug or initiation of NALT (approximately 10.6 months)
Stage 2: Number of Participants With PN	An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Participants receiving polatuzumab vedotin may develop PN, including peripheral sensory and/or motor neuropathy. Symptoms included hypoesthesia, hyperesthesia, paresthesia, dysesthesia, discomfort, a burning sensation, weakness, gait disturbance, loss of balance, orthostatic hypotension, syncope, or neuropathic pain.	From treatment initiation until 90 days after the last dose of study drug or initiation of NALT (approximately 10.6 months)
Stage 1 and Stage 2: Number of Participants With Dose Modification for Polatuzumab Vedotin	Dose modifications (interruptions/reductions) were based on physical examination findings, observed toxicities, and laboratory results obtained within 72 hours before study treatment administration. The determination of all dose modifications was made based on the investigator's assessment of ongoing clinical benefit with continuing study treatment. Dosing occurred only when a participant's clinical assessment and laboratory test values were acceptable.	Stage 1: Up to approximately 5.3 months and Stage 2: Up to approximately 7.6 months
Stage 1 and Stage 2: Dose Intensity of Polatuzumab Vedotin	Dose intensity = (total dose actually received divided by the expected total dose)*100. Expected total dose for dose intensity accounting for delay/reduction is based on the expected number of cycles between the first and last exposure of each drug. Percentage of dose intensity accounting for delay/reduction in dose by the participants in each arm is reported here.	Stage 1: Up to approximately 5.3 months and Stage 2: Up to approximately 7.6 months
Stage 1: OS	OS was defined as the time from randomization to the death from any cause during the study. Participants who were not reported as having died at the time of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization. KM method was used to estimate median OS for each treatment arm.	From randomization to the death (up to approximately 34 months)
Stage 1 and Stage 2: Percentage of Participants With Anti-drug Antibodies (ADAs) to Polatuzumab Vedotin	Treatment emergent ADA-positive participants after drug administration were determined for participants exposed to polatuzumab vedotin. Participants positive for treatment emergent ADA were defined as the number of post-baseline evaluable participants determined to have treatment-induced ADA or treatment-enhanced ADA during the study period. Treatment-induced ADA = a participant with negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Percentages are rounded off.	Up to approximately 34 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage 1: Observed Plasma Concentrations of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (acMMAE) and Unconjugated MMAE (ng/mL)	Re-classified as 'Other Pre-specified' due to sparse PK sampling, to support population PK analysis of the data which is an exploratory analysis.	Pre- and post-dose (infusion duration=90 minutes [min]) on Cycle 1 Day 1 and Cycle 4 Day 1 (Cycle length=21 days)
Stage 2: Observed Plasma Concentrations of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (acMMAE) and Unconjugated MMAE (ng/mL)	Re-classified as 'Other Pre-specified' due to sparse PK sampling, to support population PK analysis of the data which is an exploratory analysis.	Pre- and post-dose (infusion duration=90 minutes [min]) on Cycle 1 Day 1 and Cycle 4 Day 1 (Cycle length=21 days)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2020
• Primary Completion (Actual): November 29, 2024
• Study Completion (Actual): November 29, 2024

Study Registration Dates

• First Submitted: November 18, 2019
• First Submitted That Met QC Criteria: November 27, 2019
• First Posted (Actual): December 2, 2019

Study Record Updates

• Last Update Posted (Estimated): December 22, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Lymphoma; Large B-Cell; Diffuse
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Hemic and Lymphatic Diseases; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Antibodies, Monoclonal, Murine-Derived; Oxaliplatin; Rituximab; Gemcitabine; polatuzumab vedotin
• Other Study ID Numbers: MO40598; 2018-003727-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/innovation/process/clinical-trials/data-sharing/).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No