Phase 2
Completed N=231
A Study of Pinatuzumab Vedotin (DCDT2980S) Combined With Rituximab or Polatuzumab Vedotin (DCDS4501A) Combined With Rituximab or Obinutuzumab in Participants With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma (NHL)
Source: ClinicalTrials.gov NCT01691898 ↗Enrolled (actual)
231
Serious AEs
37.2%
Results posted
Apr 2018
Primary outcomePrimary: Percentage of Participants With a Best Overall Response (OR) of Complete Response (CR) or Partial Response (PR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C) — 59.5; 61.9; 53.8; 70.0 percentage of participants
Summary
This multicenter, open-label study will evaluate the safety and efficacy of pinatuzumab vedotin (DCDT2980S) or polatuzumab vedotin (DCDS4501A) in combination with rituximab (RTX), as well as of polatuzumab vedotin in combination with obinutuzumab in participants with relapsed or refractory (r/r) follicular lymphoma (FL) and r/r diffuse large B-cell lymphoma (DLBCL).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With a Best Overall Response (OR) of Complete Response (CR) or Partial Response (PR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C) |
59.5; 61.9; 53.8; 70.0; 75.0 | — |
| PRIMARY Duration of Objective Response (DOR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C) |
6.24; 6.47; 13.37; 9.36; 12.85 | — |
| PRIMARY Percentage of Participants With CR at End of Treatment (EOT) Based on Positron Emission Tomographic/Computed Tomography (PET/CT) Assessment Determined by Independent Review Committee (IRC) Per Lugano 2014 Response Criteria: Cohorts E, G, and H |
0; 50.0; 35.3; 0 | — |
| SECONDARY Number of Participants With Anti-Drug Antibodies (ADA) to Pinatuzumab Vedotin |
2; 0; 0 | — |
| SECONDARY Number of Participants With ADA to Polatuzumab Vedotin |
1; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With ADA to Obinutuzumab |
1; 2; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With PD as Determined by Modified Response and Progression Criteria for NHL or Death Due to Any Cause: Rituximab Containing Regimens (Arms A and B, Cohort C) |
85.7; 52.4; 76.9; 55.0; 60.0 | — |
| SECONDARY Progression-free Survival (PFS) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C) |
5.388; 12.682; 5.552; 15.277; 18.103 | — |
| SECONDARY Percentage of Participants Who Died Due to Any Cause: Rituximab Containing Regimens (Arms A and B, Cohort C) |
66.7; 23.8; 61.5; 15.0; 20.0 | — |
| SECONDARY Overall Survival (OS): Rituximab Containing Regimens (Arms A and B, Cohort C) |
16.493; NA; 18.760; NA; NA | — |
| SECONDARY Percentage of Participants With CR at EOT Based on PET/CT Assessment as Determined by Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H) |
25.0; 66.7; 33.3; 15.2 | — |
| SECONDARY Percentage of Participants With OR at EOT Based on PET/CT Assessment as Determined by IRC Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H) |
25.0; 100.0; 64.7; 18.5 | — |
| SECONDARY Percentage of Participants With OR at EOT Based on PET/CT Assessment as Determined by the Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H) |
25.0; 66.7; 63.9; 21.2 | — |
| SECONDARY Percentage of Participants With CR at EOT Based on CT Assessment Alone as Determined by IRC Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G) |
6.5; 13.9 | — |
| SECONDARY Percentage of Participants With CR at EOT Based on CT Assessment Alone as Determined by Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G) |
10.8; 20.5 | — |
| SECONDARY Percentage of Participants With OR at EOT Based on CT Assessment Alone as Determined by IRC Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G) |
25.8; 66.7 | — |
| SECONDARY Percentage of Participants With OR at EOT Based on CT Assessment Alone as Determined by Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G) |
21.6; 64.1 | — |
| SECONDARY Percentage of Participants With Best OR Based on PET/CT or CT Assessment as Determined by Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H) |
20.0; 50.0; 74.4; 43.6 | — |
| SECONDARY Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C) |
5640; 3350; 4200; 3910; 2660 | — |
| SECONDARY Maximum Observed Concentration (Cmax) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C) |
217; 225; 232; 228; 227 | — |
| SECONDARY Systemic Clearance (CL) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C) |
113.97; 124.53; 116.26; 134.31; 158.57 | — |
| SECONDARY Half-Life (t1/2) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C) |
35.3; 18.7; 25.6; 19.8; 14.4 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C) |
2901.85; 2802.96; 2988.90; 2839.26; 2654.46 | — |
| SECONDARY AUCinf of Total Antibody for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab |
309; 315 | — |
| SECONDARY AUCinf of Antibody Conjugated Monomethyl Auristatin E (acMMAE) for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab |
2840; 3110 | — |
| SECONDARY Area Under the Concentration-Time Curve From Time Zero To Last Measurable Concentration (AUClast) of Unconjugated MMAE for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab |
34.2; 33.5 | — |
| SECONDARY Cmax of Total Antibody for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab |
42.5; 48.3 | — |
| SECONDARY Cmax of acMMAE for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab |
850; 994 | — |
| SECONDARY Cmax of Unconjugated MMAE for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab |
4.39; 4.20 | — |
| SECONDARY AUCinf of Total Antibody for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab |
412; 428 | — |
| SECONDARY AUCinf of acMMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab |
3660; 3510 | — |
| SECONDARY AUClast of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab |
31.7; 29.5 | — |
| SECONDARY Cmax of Total Antibody for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab |
51.9; 55.9 | — |
| SECONDARY Cmax of acMMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab |
948; 968 | — |
| SECONDARY Cmax of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab |
3.72; 3.29 | — |
| SECONDARY AUCinf of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab |
258 | — |
| SECONDARY AUCinf of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab |
2600 | — |
| SECONDARY AUClast of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab |
17.7 | — |
| SECONDARY Cmax of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab |
42.2 | — |
| SECONDARY Cmax of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab |
787 | — |
| SECONDARY Cmax of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab |
2.02 | — |
| SECONDARY AUCinf of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab |
218; 215 | — |
| SECONDARY AUCinf of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab |
2440; 2340 | — |
| SECONDARY AUClast of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab |
27.9; 22.3 | — |
| SECONDARY Cmax of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab |
35.0; 34.2 | — |
| SECONDARY Cmax of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab |
711; 694 | — |
| SECONDARY Cmax of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab |
3.62; 2.80 | — |
| SECONDARY Cmax of Obinutuzumab: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G) |
340; 330 | — |
| SECONDARY Overall Survival (OS): Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G) |
10.5; NA | — |
| SECONDARY Percentage of Participants Who Died Due to Any Cause: Obinutuzumab Containing Cohorts (Cohorts E + H and E + G) |
77.8; 20.5 | — |
| SECONDARY Progression-free Survival (PFS) as Determined by Modified Response and Progression Criteria for NHL: Obinutuzumab Containing Cohorts (Cohorts E + H and E + G) |
2.7; 19.5 | — |
| SECONDARY Percentage of Participants With PD as Determined by Modified Response and Progression Criteria for NHL or Death Due to Any Cause: Obinutuzumab Containing Cohorts (Cohorts E + H and E + G) |
88.9; 56.8 | — |
Eligibility Criteria
Inclusion Criteria
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
- Life expectancy of at least 12 weeks
- History of histologically documented r/r Grades 1 to 3a FL, or r/r DLBCL
- Availability of an archival or freshly biopsied tumor tissue sample must be confirmed for study enrollment
- Have a clinical indication for treatment as determined by the investigator
- Must have at least one bi-dimensionally measurable lesion (greater than [>] 1.5 centimeters [cm] in its largest dimension by CT scan or Magnetic Resonance Imaging [MRI])
Exclusion Criteria
- Prior use of any monoclonal antibody, radio-immuno-conjugate or antibody drug conjugate within 4 weeks before study start
- Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational anti-cancer agent within 2 weeks prior study start
- Adverse events except for sensory neuropathy from any previous treatments must be resolved or stabilized to Grade less than equal to ( 1 peripheral neuropathy
- Vaccination with a live vaccine within 28 days prior to treatment
Data sourced from ClinicalTrials.gov (NCT01691898). 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.