Non-Hodgkin Lymphoma
Conditions
Brief summary
This study will assess the efficacy and safety of mosunetuzumab in combination with polatuzumab vedotin (M+P) in participants with relapsed or refractory (R/R) diffuse-large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, transformed follicular lymphoma (trFL) and FL Grade 3B (FL3B) in comparison with a commonly used regimen in this participant population, rituximab, gemcitabine and oxaliplatin (R-GemOx).
Interventions
DRUGMosunetuzumab
Participants will receive SC mosunetuzumab on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-8 (cycle length = 21 days).
DRUGPolatuzumab vedotin
Participants will receive IV polatuzumab vedotin every three weeks (Q3W) for 6 cycles (cycle length = 21 days).
DRUGTocilizumab
Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS) events.
DRUGRituximab
Participants will receive IV rituximab on Day 1 of each cycle for 8 cycles (cycle length = 14 days).
DRUGGemcitabine
Participants will receive IV gemcitabine on Day 1 of each cycle for 8 cycles (cycle length = 14 days).
DRUGOxaliplatin
Participants will receive IV oxaliplatin on Day 1 of each cycle for 8 cycles (cycle length = 14 days).
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 * CD20+ aggressive lymphoma as determined by the local hemopathology laboratory from the following diagnoses by 2016 World Health Organization classification of lymphoid neoplasms: DLBCL, not otherwise specified (NOS); high-grade B-cell lymphoma (NOS or double/triple hit); transformed follicular lymphoma; follicular lymphoma Grade 3b * Have disease relapsed or refractory to at least one prior systemic therapy for aggressive non-Hodgkin's lymphoma (aNHL) * Participants who have received only one prior line of therapy must be ineligible for autologous stem cell transplant (ASCT) * Measurable disease * Adequate hepatic, hematologic, and renal function * Estimated creatinine clearance (CrCl) ≥ 30 mL/min by Cockroft-Gault method or other institutional standard methods * Negative HIV test at screening. Participants with a positive HIV test at screening are eligible provided that, prior to enrollment, they are stable on anti-retroviral therapy for at least 4 weeks, have a CD4 count of at least 200 microliters, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months
Exclusion criteria
* Pregnant or breast feeding, or intending to become pregnant during the study or within 3 months after the final dose of mosunetuzumab, 9 months after the final dose of polatuzumab vedotin, 12 months after the final dose of rituximab, 6 months after the final dose of gemcitabine, 9 months after the final dose of oxaliplatin, and 3 months after the final dose of tocilizumab, as applicable * Inability to comply with protocol-mandated activity restrictions * Prior treatment with mosunetuzumab or other CD-20-directed bispecific antibodies, or R-GemOx or Gem-Ox * Prior treatment with polatuzumab vedotin, with the following exceptions: participants who have a documented response (partial response or complete response) to polatuzumab vedotin and an absence of PD within 12 months from the last dose of polatuzumab vedotin; participants who received up to 2 doses of a polatuzumab vedotin-containing regimen as bridging to CAR-T therapy, and either has a documented disease control (stable disease, partial response, or complete response), or were not assessed for response following treatment with polatuzumab vedotin * Contraindication to any component of the study treatment * Grade \> 1 peripheral neuropathy * Participants with Grade \> 1 persistent toxicity related to prior anti-lymphoma treatment (except for alopecia and anorexia, or other toxicities not considered a safety risk for the participant per investigator's judgment) * Received anti-lymphoma treatments with monoclonal antibodies, radio-immunoconjugates or antibody-drug conjugates (ADCs) within 4 weeks before the first dose of study treatment * Treatment with any chemotherapeutic agent, or treatment with any other anti-lymphoma agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to the first dose of study treatment * Treatment with radiotherapy within 2 weeks prior to the first dose of study treatment * ASCT within 100 days prior to the first study treatment administration * Prior treatment with chimeric antigen receptor (CAR) T cell therapy within 30 days before the first study treatment administration * Prior allogenic stem cell transplant (SCT) * Have had a solid organ transplantation * Known or suspected history of hemophagocytic lymphohistiocytosis (HLH) * History of confirmed progressive multifocal leukoencephalopathy * History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombination antibody-related fusion proteins) * History of other malignancy that could affect compliance with the protocol or interpretation of results, with the exception of malignancies with a negligible risk of metastasis or death * Currently have or have had a past history of central nervous system (CNS) involvement of lymphoma * Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease. Participants with a history of stroke who have not experienced a stroke or transient ischemic attack in the past 2 years and have no residual neurologic deficits as judged by the investigator, or with a history of epilepsy who have had no seizures in the past 2 years while not receiving any anti-epileptic medications, are allowed * Significant cardiovascular disease such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina * Significant active pulmonary disease * Participants with active symptoms of interstitial lung disease and/or pneumonitis, or those with a history of interstitial lung disease and/or pneumonitis within 6 months prior to the first dose of study treatment * Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of the nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 2 weeks prior to the first study treatment administration * Known or suspected chronic active Epstein-Barr virus (EBV) infection * Recent major surgery within 4 weeks prior to the first study treatment administration * Positive test results for chronic hepatitis B infection * Acute or chronic hepatitis C virus (HCV) infection * Have been administered a live, attenuated vaccine within 4 weeks before the first dose of study treatment administration or anticipation that such a live, attenuated vaccine will be required during the study * Participants who have positive SARS-CoV-2 test within 7 days prior to enrollment (rapid antigen test result is acceptable) * History of autoimmune disease * Received investigational therapy, whether or not intended for lymphoma treatment, within 7 days prior to initiation of study treatment * Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) as Determined by the Independent Review Facility (IRF), According to Lugano Response Criteria 2014 (LRC) Using Positron Emission Tomography-computed Tomography (PET-CT) or CT Scans in Interim Analysis Population (IAP) | Up to approximately 23.8 months | ORR was defined as the percentage of participants with complete response (CR)/partial response (PR), per IRF, per Lugano Response Criteria. Percentages have been rounded off. |
| Progression-free Survival (PFS) as Determined by the IRF, According to LRC Using PET-CT or CT Scans | Up to 32 months | PFS was defined as the time from randomization to first occurrence of disease progression (PD) or death from any cause, whichever occurred first, per IRF, per Lugano Response Criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR as Determined by the IRF, According to LRC Using PET-CT or CT Scans in ITT Population | Up to 32 months | ORR was defined as the percentage of participants with complete response (CR)/partial response (PR), per IRF, per Lugano Response Criteria. Percentages have been rounded off. |
| ORR as Determined by the Investigator, According to LRC Using PET-CT or CT Scans in ITT Population | Up to approximately 58 months | ORR was defined as the percentage of participants with CR or PR, as determined by the investigator, per Lugano Response Criteria. |
| Duration of Response (DoR) as Determined by the IRF, According to LRC Using PET-CT or CT Scans | Up to 32 months | DoR was defined as the time from first occurrence of documented PET-CT and/or CT-based objective response (OR) (CR/PR) to PD, or death from any cause, whichever occurred first, per IRF, per Lugano Response Criteria. |
| DoR as Determined by the Investigator, According to LRC Using PET-CT or CT Scans | Up to approximately 58 months | DoR=time from first occurrence of documented PET-CT and/or CT-based objective response (OR) (CR/PR) to PD, or death from any cause, whichever occurred first, per investigator, per Lugano Response Criteria. |
| Overall Survival (OS) | Up to 32 months | OS was defined as the time from randomization to death from any cause. K-M method was used to estimate median OS. |
| PFS as Determined by the Investigator, According to LRC Using PET-CT or CT Scans | Up to approximately 58 months | PFS was defined as the time from randomization to first occurrence of PD or death from any cause, whichever occurred first, as determined by the investigator, per Lugano Response Criteria. |
| Complete Response Rate (CRR) as Determined by the IRF, According to LRC Using PET-CT or CT Scans | Up to approximately 58 months | CRR was defined as the percentage of participants in whom CR was observed at any time during the study, based on PET-CT and/or CT scans, as determined by the IRF, per Lugano Response Criteria. |
| CRR as Determined by the Investigator, According to LRC Using PET-CT or CT Scans | Up to approximately 58 months | CRR was defined as the percentage of participants in whom CR was observed at any time during the study, based on PET-CT and/or CT scans, as determined by the investigator, per Lugano Response Criteria. |
| Duration of Complete Response (DOCR) as Determined by the IRF, According to LRC Using PET-CT or CT Scans | Up to 32 months | DOCR was defined as the time from first occurrence of a documented CR to PD, per IRF, per Lugano Response Criteria. |
| DOCR as Determined by the Investigator, According to LRC Using PET-CT or CT Scans | Up to approximately 58 months | DOCR=time from first occurrence of documented CR to PD, as determined by the investigator, per Lugano Response Criteria. |
| Time to Deterioration in Physical Functioning (PF), as Measured by the European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire-Core 30 (EORTC QLQ-C30) | Up to approximately 58 months | Time to deterioration in PF was defined as time from randomization to the first documentation of 10-point or more decrease, from baseline. EORTC QLQ-C30 is cancer-specific instrument consisting of 30 questions to evaluate 5 aspects of participant functioning (physical, emotional, role, cognitive, \& social), 3 symptom scales (fatigue, nausea, vomiting, \& pain), global health status (GHS)/quality of life (QoL), \& 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea \& financial difficulties). Functioning scales were scored on a 4-point scale, ranging from 1=Not at all to 4=Very much. All EORTC scales \& single-item measures were linearly transformed to a score range of 0-100. High score for a functioning scale indicated high/healthy level of functioning. |
| Time to Deterioration in Fatigue Scale, as Measured by the EORTC QLQ-C30 | Up to approximately 58 months | Time to deterioration in fatigue was defined as time from randomization to the first documentation of 10-point or more decrease, from baseline. EORTC QLQ-C30 is cancer-specific instrument consisting of 30 questions to evaluate 5 aspects of participant functioning (physical, emotional, role, cognitive, \& social), 3 symptom scales (fatigue, nausea, vomiting, \& pain), global health status (GHS)/quality of life (QoL), \& 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea \& financial difficulties). Fatigue scale was scored on a 4-point scale, ranging from 1=Not at all to 4=Very much. All EORTC scales \& single-item measures were linearly transformed to a score range of 0-100. High score for a fatigue scale indicated a high level of symptom severity. |
| Time to Deterioration in Lymphoma Symptoms, as Measured by Functional Assessment of Cancer Therapy- Lymphoma Questionnaire (FACT- Lym LymS) | Up to approximately 58 months | Time to deterioration in lymphoma-specific symptoms was defined as the time from randomization to the first documentation of a 3-point or more decrease, from baseline. FACT-Lym is a cancer-specific scale used to assess health-related QoL aspects relevant to participants with lymphoma. The full measure consists of the FACT-G physical, social/family, emotional, and functional well-being scales (27 items), as well as lymphoma-specific symptoms subscale (LymS). The FACT-Lym Lyms consists of 15 items scored from 0-4, where 0="Not at all" and 4="very much". Scale score ranges from 0 to 60, where a high score indicated a better QoL. |
| Number of Participants With Adverse Events (AEs) | Up to approximately 58 months | An AE was defined as any untoward medical occurrence in a participant or clinical study participant temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. |
| Number of Participants With Cytokine Release Syndrome (CRS) With Severity Determined by the American Society for Transplantation and Cell Therapy (ASTCT) Consensus Grading Scale | Up to approximately 58 months | CRS=supraphysiologic response following administration of any immune therapy that results in activation/engagement of endogenous or infused T cells and/or other immune effector cells. Symptoms may be progressive, including fever at onset, and may also include hypotension, capillary leak (hypoxia), and end-organ dysfunction. Severity of CRS was determined per ASTCT Consensus Grading Criteria, which categorizes CRS into 5 grades- Grade 1: Fever (≥38◦Celsius), with/without constitutional symptoms, in absence of hypotension \& hypoxia; Grade 2: Fever with hypotension not requiring vasopressors and/or hypoxia requiring low-flow oxygen; Grade 3: Fever with hypotension requiring one vasopressor, with/without vasopressin, and/or hypoxia requiring high-flow oxygen; Grade 4: Fever accompanied by hypotension requiring multiple vasopressors (excluding vasopressin) and/or hypoxia requiring positive-pressure ventilation; Grade 5: death due to CRS. |
| Number of Participants With Dose Interruptions, Dose Reductions and Study Treatment Discontinuation Due to AEs | Up to approximately 58 months | An AE was defined as any untoward medical occurrence in a participant or clinical study participant temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the study intervention. Participants who had dose interruptions or modifications or who discontinued study treatment due to AEs will be reported here. |
| Dose Intensity of Mosunetuzumab | Up to approximately 58 months | — |
| Change From Baseline in Peripheral Neuropathy (PN), as Measured by the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) | Up to approximately 58 months | The FACT/GOG-Ntx is an 11-item patient-reported outcome that measures polatuzumab vedotin-induced PN. The scale contains 4 subscales to assess sensory neuropathy (4 items), hearing neuropathy (2 items), motor neuropathy (3 items), and dysfunction associated with neuropathy (2 items), which can be summed to create a total score. Each item is scored on a 5-point response scale that ranges from 0=not at all to 4=very much. The possible range for the scores is 0-44, with higher scores indicating more extreme neuropathy. |
Countries
Argentina, Brazil, Canada, China, Israel, Japan, Mexico, New Zealand, Peru, South Korea, Thailand, Turkey (Türkiye), United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Participant flow
Recruitment details
A total of 208 participants with relapsed or refractory (R/R) diffuse-large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, transformed follicular lymphoma (trFL), and follicular lymphoma (FL) Grade 3B (FL3B), ineligible for autologous stem cell transplant (ASCT), took part in the study at 54 investigative sites across 13 countries. The study is still ongoing.
Pre-assignment details
Participants were randomized in a 2:1 ratio to receive either mosunetuzumab in combination with polatuzumab vedotin (Mosun-Pola) (Arm A) or rituximab in combination with gemcitabine plus oxaliplatin (R-GemOx) (Arm B).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 60.2 years STANDARD_DEVIATION 14.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 14 Participants |
| Race (NIH/OMB) Asian | 82 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 99 Participants |
| Sex: Female, Male Female | 87 Participants |
| Sex: Female, Male Male | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 66 / 135 | 35 / 64 |
| other Total, other adverse events | 129 / 135 | 60 / 64 |
| serious Total, serious adverse events | 45 / 135 | 16 / 64 |
Outcome results
None listed