Phase 2
Completed N=117
A Phase Ib/II Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With CHOP or CHP-Polatuzumab Vedotin in Participants With B-Cell Non-Hodgkin Lymphoma
Source: ClinicalTrials.gov NCT03677141 ↗Enrolled (actual)
117
Serious AEs
52.2%
Results posted
Dec 2024
Primary outcomePrimary: Complete Response (CR) Rate at the Time of Primary Response Assessment (PRA) Based on Positron Emission Tomography - Computed Tomography (PET-CT) as Determined by Independent Review Committee (IRC) — 72.5; 77.3 Percentage of participants
Summary
This study will evaluate the safety, pharmacokinetics, and preliminary efficacy of mosunetuzumab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (M-CHOP) and, subsequently, in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) plus polatuzumab vedotin (CHP-pola) in participants with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (NHL), and in previously untreated participants with diffuse large B-cell lymphoma (DLBCL).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Complete Response (CR) Rate at the Time of Primary Response Assessment (PRA) Based on Positron Emission Tomography - Computed Tomography (PET-CT) as Determined by Independent Review Committee (IRC) |
72.5; 77.3 | — |
| SECONDARY CR Rate at PRA Based on CT Only as Determined by the Investigator (Phase II) |
50.0; 47.5; 31.8 | — |
| SECONDARY Overall Response Rate (ORR) at PRA Based on PET-CT as Determined by the Investigator (Phase II) |
87.5; 80.0; 77.3 | — |
| SECONDARY ORR at PRA Based on CT Only as Determined by the Investigator (Phase II) |
85.0; 72.5; 81.8 | — |
| SECONDARY Best ORR Based on PET-CT and/or CT Scan as Determined by the Investigator (Phase II) |
95.0; 85.0; 95.5 | — |
| SECONDARY Duration of Response (DOR) as Determined by the Investigator (Phase II) |
NA; NA; NA | — |
| SECONDARY Progression-free Survival (PFS) as Determined by the Investigator (Phase II) |
NA; NA; NA | — |
| SECONDARY PFS at 1 Year as Determined by the Investigator (Phase II) |
77.47; 70.83; 81.82 | — |
| SECONDARY Event-free Survival (EFS) as Determined by the Investigator (Phase II) |
NA; NA; NA | — |
| SECONDARY Time to Deterioration in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale |
NA; 6.5 | — |
| SECONDARY Time to Deterioration in Physical Functioning and Fatigue as Measured by the European Organization for Research and Treatment of Cancer Quality of Life - Core 30 Questionnaire (EORTC QLQ-C30) |
2.3; 2.3 | — |
| SECONDARY Polatuzumab Vedotin Serum Concentrations |
0.993; 1.99; 1.73; 2.76; 8.13; 5.8 | — |
| SECONDARY Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations |
620; 668; 584; 219; 115; 275 | — |
| SECONDARY Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations |
0.535; 0.55; 0.432; 1.94; 3.3; 2.82 | — |
| SECONDARY Mosunetuzumab Serum Concentrations |
0.157; 0.181; 0.155; 0.132; 0.152; 0.163 | — |
| SECONDARY Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab |
0; 0; 0; 0; 0; 3 | — |
| SECONDARY Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin |
0; 1; 2; 8; 32; 19 | — |
Eligibility Criteria
Inclusion Criteria for Phase Ib and Phase II Portions
- At least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or one bi-dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest diameter
- Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2
- Adequate hematologic function
Inclusion Criteria for Phase Ib Portion
Participants must also meet the following criteria for study entry into the Phase Ib portion:
- Histologically confirmed B-cell NHL according to the World Health Organization (WHO) 2016 classification expected to express the cluster of differentiation-20 (CD20) antigen
- Relapsed or refractory (R/R) B-cell NHL after at least one prior systemic lymphoma therapy
- Treatment with at least one prior CD20-directed therapy
- Group B only: no prior treatment with polatuzumab vedotin
Inclusion Criteria for Phase II Portion
Participants must also meet the following criteria for study entry in the Phase II portion:
- Previously untreated, histologically confirmed DLBCL according to WHO 2016 classification
- International Prognostic Index (IPI) score of 2-5
Exclusion Criteria
- Prior treatment with mosunetuzumab
- Prior allogenic stem-cell transplant
- Current Grade >1 peripheral neuropathy
- Participants with history of confirmed progressive multifocal leukoencephalopathy (PML)
- Known or suspected chronic active Epstein Barr virus (CAEBV), hepatitis B, hepatitis C (HCV), or Human Immunodeficiency Virus (HIV)
- Prior solid organ transplantation
- History of autoimmune disease
- Current or past history of central nervous system (CNS) lymphoma
- Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
- Significant cardiovascular disease or pulmonary disease
- Clinically significant history of liver disease
- Recent major surgery within 4 weeks before the start of C1D1, other than superficial lymph node biopsies for diagnosis
Exclusion Criteria for Phase Ib Portion
Participants who also meet any of the following criteria will be excluded from study entry in the Phase Ib portion:
- Prior treatment with chemotherapy, immunotherapy, and biologic therapy 4 weeks prior to C1D1
- Prior treatment with radiotherapy within 2 weeks prior to C1D1
- Adverse events from prior anti-cancer therapy resolved to ≤Grade 1 (with the exception of alopecia and anorexia)
- Prior treatment with >250 mg/m^2 doxorubicin (or equivalent anthracycline dose)
Exclusion Criteria for Phase II Portion
Participants who also meet any of the following criteria will be excluded from study entry in the Phase II portion:
- Participants with transformed lymphoma
- Prior therapy for B-cell NHL
Data sourced from ClinicalTrials.gov (NCT03677141). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.