Phase 2
Completed N=82
A Study of Polatuzumab Vedotin in Combination With Rituximab or Obinutuzumab, Cyclophosphamide, Doxorubicin, and Prednisone in Participants With B-Cell Non-Hodgkin's Lymphoma
Lymphoma, Non Hodgkin
Source: ClinicalTrials.gov NCT01992653 ↗
Enrolled (actual)
82
Serious AEs
37.8%
Results posted
Mar 2020
Primary outcomePrimary: Number of Participants With Adverse Events in Diffuse Large B-Cell Lymphoma (DLBCL) Population — 2; 3; 5; 0 Participants
Summary
This multicenter, open-label, dose-escalation study will evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of polatuzumab vedotin in combination with rituximab or obinutuzumab, cyclophosphamide, doxorubicin, and prednisone (CHP chemotherapy) in participants with non-Hodgkin's lymphoma (NHL). Participants will receive escalating doses of polatuzumab vedotin intravenously (IV) every 3 weeks in combination with standard doses of rituximab plus CHP chemotherapy (R-CHP) or obinutuzumab plus CHP chemotherapy (G-CHP). Participants will be treated for a total of six or eight cycles in accordance with local institutional practice. Two parallel treatment arms will explore doses of polatuzumab vedotin in combination with R-CHP or G-CHP. The maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of polatuzumab vedotin in combination with R-CHP will be identified before it is combined with G-CHP. Once the MTD or RP2D is determined, polatuzumab vedotin will be dosed at MTD or RP2D -1 in combination with G-CHP to start the dose escalation of this combination.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events in Diffuse Large B-Cell Lymphoma (DLBCL) Population |
2; 3; 5; 0; 4; 4 | — |
| PRIMARY Number of Participants With Adverse Events in Non-DLBCL Population |
1; 0; 1; 1; 2; 2 | — |
| PRIMARY Number of Participants With Dose Limiting Toxicities (DLTs) in DLBCL Population |
0; 0; 1; 0; 1; 0 | — |
| PRIMARY Number of Participants With DLTs in Non-DLBCL Population |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population |
50.0; 100.0; 100.0; 75.0; 100.0; 75.0 | — |
| SECONDARY Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population |
100.0; 100.0; 100.0; 100.0; 100.0; 0 | — |
| SECONDARY Number of Participants With Anti-Polatuzumab Vedotin Antibodies |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Anti-Obinutuzumab Antibodies |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Area Under the Concentration-Time Curve (AUC) of Polatuzumab Vedotin |
1300; 1510; 2600; 4090; 1940; 1850 | — |
| SECONDARY Maximum Concentration (Cmax) of Polatuzumab Vedotin |
373; 537; 781; 1400; 537; 557 | — |
| SECONDARY Clearance (CL) of Polatuzumab Vedotin |
14.0; 17.3; 12.8; 10.5; 13.2; 18.7 | — |
| SECONDARY Terminal Half-Life (t1/2) of Polatuzumab Vedotin |
5.03; 4.85; 4.79; 4.42; 5.19; 4.89 | — |
| SECONDARY Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin |
58.2; 80.0; 57.7; 41.9; 67.9; 87.5 | — |
| SECONDARY Plasma Levels of Cyclophosphamide |
37.5; 32.3; 23.2; 22.5; 2.98; 3.32 | — |
| SECONDARY Plasma Levels of Doxorubicin |
35.4; 30.2; 9.13; 11.7; 29.3; 29.6 | — |
| SECONDARY Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score |
0; 0.32; 0; 0.91; 0.02; 0.07 | — |
| SECONDARY Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score |
0; 0; 0; 1; 0.25; 0 | — |
| SECONDARY Duration of Response, as Assessed by Investigator Using Cheson Criteria for DLBCL Population |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Duration of Response, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population |
NA; 4.11; NA; NA; NA | — |
| SECONDARY Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population |
NA; 6.87; NA; NA; NA | — |
| SECONDARY Event Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population |
NA; NA; NA; NA; NA; 35.45 | — |
| SECONDARY Event Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population |
NA; 6.87; 6.70; NA; NA | — |
| SECONDARY Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for DLBCL Population |
100.70; 99.97; 96.04; 99.35; 99.95; 96.71 | — |
| SECONDARY Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for Non-DLBCL Population |
100.00; 100.94; 132.22; 99.72; 100.17 | — |
| SECONDARY Overall Survival for DLBCL Population |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Overall Survival for Non-DLBCL Population |
NA; 15.24; NA; NA; NA | — |
Eligibility Criteria
Inclusion Criteria
All Participants:
- At least one bi-dimensionally measurable lesion, defined as greater than (>) 1.5 centimeters (cm) in its longest dimension
- Life expectancy of at least 24 weeks
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Adequate hematologic function (unless inadequate function is due to underlying disease, as established by extensive bone marrow involvement or is due to hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator)
- Agreement to use highly effective contraception measures. Women of childbearing potential must agree to remain abstinent or use contraceptive measures that result in a failure rate of ) 1 peripheral neuropathy
- Ongoing corticosteroid use of >30 milligrams per day (mg/day) of prednisone/prednisolone or equivalent. Participants receiving corticosteroid treatment with less than or equal to (</=) 30 mg/day of prednisone/prednisolone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration before Cycle 1 Day 1
- Primary central nervous system (CNS) lymphoma
- Vaccination with live vaccines within 6 months before Cycle 1 Day 1
- History of other malignancy that could affect compliance with the protocol or interpretation of results. Participants with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix are eligible. Participants with a malignancy that has been treated with surgery alone with curative intent will also be excluded unless the malignancy has been in documented remission without treatment for greater than or equal to (</=) 5 years before enrollment
- Evidence of significant, uncontrolled concomitant diseases, including renal disease that would preclude chemotherapy administration, or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
- Significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, congestive heart failure, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of 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 4 weeks before Cycle 1 Day 1
- Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
- Positive for hepatitis B or hepatitis C infection
- Prior radiotherapy to the mediastinal/pericardial region
- Pregnant or lactating women
- Recent major surgery within 6 weeks before the start of Cycle 1 Day 1
Data sourced from ClinicalTrials.gov (NCT01992653). 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.