Phase 1
Completed N=189
A Study Of PF-05082566 As A Single Agent And In Combination With Rituximab
Lymphoma, Non-Hodgkin · Lymphoma, Follicular · Lymphoma, Large B-Cell, Diffuse · Non-Small Cell Lung Cancer
Source: ClinicalTrials.gov NCT01307267 ↗
Enrolled (actual)
189
Serious AEs
20.6%
Results posted
Mar 2020
Primary outcomePrimary: Number of Participants With Dose-Limiting Toxicities (DLTs) in First 2 Cycles of Portion A — 0; 0; 0; 0 Participants
Summary
A study of PF-05082566, a 4-1BB agonist monoclonal antibody (mAb), in patients with solid tumors or b-cell lymphomas, and in combination with rituximab in patients with CD20 positive Non-Hodgkin's Lymphoma (NHL).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose-Limiting Toxicities (DLTs) in First 2 Cycles of Portion A |
0; 0; 0; 0; 0; 1 | — |
| PRIMARY Number of Participants With DLTs in First 2 Cycles of Portion B |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) in Portion A |
3; 3; 5; 4; 3; 39 | — |
| SECONDARY Number of Participants With Treatment-Emergent AEs by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade in Portion A |
0; 0; 1; 1; 1; 9 | — |
| SECONDARY Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A |
1; 3; 3; 3; 1; 20 | — |
| SECONDARY Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A |
1; 1; 1; 1; 0; 1 | — |
| SECONDARY Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion A |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY PF-05082566 Maximum Observed Serum Concentration (Cmax) in Portion A |
0.1515; 0.4952; 1.014; 2.614; 4.219; 3.246 | — |
| SECONDARY PF-05082566 Pre-dose Trough Concentration During Multiple Dosing (Ctrough) in Portion A |
NA; 0.1063; 0.1092; 0.3268; 0.4285; 0.3868 | — |
| SECONDARY PF-05082566 Time for Maximum Observed Serum Concentration (Tmax) in Portion A |
1.75; 1.63; 2.00; 1.26; 1.25; 1.03 | — |
| SECONDARY PF-05082566 Area Under the Serum Concentration-Time Profile (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUClast) in Portion A |
8.212; 101.0; 148.1; 389.4; 703.3; 481.1 | — |
| SECONDARY PF-05082566 AUC From Time 0 to Infinity (AUCinf) in Portion A |
120; 187.5; 667.0; 989.5; 687.9; 770.0 | — |
| SECONDARY PF-05082566 AUC From Time 0 to Time of Dosing Interval (AUCtau) in Portion A |
13.70; 104.8; 154.2; 503.9; 690.9; 538.6 | — |
| SECONDARY PF-05082566 Clearance (CL) in Portion A |
0.2510; 0.3203; 0.1800; 0.1823; 0.3490; 0.3890 | — |
| SECONDARY PF-05082566 Volume of Distribution at Steady State (Vss) in Portion A |
65.50; 101.1; 83.63; 74.38; 110.7; 75.20 | — |
| SECONDARY Number of Participants With Positive Anti-Drug Antibody (ADA) for PF-05082566 in Portion A |
4; 2; 5; 0; 0; 20 | — |
| SECONDARY Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion A |
1; 0; 0; 2; 0; 10 | — |
| SECONDARY Percentage of Participants Achieving Objective Response Per Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 in Portion A |
0; 0; 0; 0; 0; 4.8 | — |
| SECONDARY Duration of Response in Portion A |
5.8; 24.2; 22.8 | — |
| SECONDARY Time to Response in Portion A |
10.3; 1.8 | — |
| SECONDARY Progression-Free Survival in Portion A |
1.7; 3.6; 1.7; 3.5; 1.7; 2.1 | — |
| SECONDARY Overall Survival in Portion A |
4.6; 4.0; 7.6; 13.3; 5.9; 9.0 | — |
| SECONDARY Number of Participants With Treatment-Emergent AEs and SAEs in Portion B |
3; 3; 4; 3; 3; 3 | — |
| SECONDARY Number of Participants With Treatment-Emergent AEs by Maximum NCI CTCAE Grade in Portion B |
0; 0; 1; 0; 1; 1 | — |
| SECONDARY Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B |
3; 2; 2; 2; 1; 1 | — |
| SECONDARY Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B |
1; 2; 0; 1; 0; 1 | — |
| SECONDARY Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion B |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY PF-05082566 Cmax in Portion B |
0.6284; 1.569; 2.673; 4.167; 4.512; 7.435 | — |
| SECONDARY PF-05082566 Ctrough in Portion B |
0.1267; 0.2853; 0.3922; 0.4698; 0.3539; 0.6001 | — |
| SECONDARY PF-05082566 Tmax in Portion B |
1.50; 1.52; 1.06; 2.00; 1.52; 1.17 | — |
| SECONDARY PF-05082566 AUClast in Portion B |
121.1; 342.6; 513.7; 854.1; 701.7; 1130 | — |
| SECONDARY PF-05082566 AUCinf in Portion B |
137.8; 407.0; 615.5; 1076; 824.1; 1421 | — |
| SECONDARY PF-05082566 AUCtau in Portion B |
125.0; 345.0; 514.5; 871.6; 712.0; 1128 | — |
| SECONDARY PF-05082566 CL in Portion B |
0.2178; 0.1470; 0.1950; 0.1667; 0.2911; 0.2107 | — |
| SECONDARY PF-05082566 Vss in Portion B |
81.87; 78.60; 79.93; 66.90; 93.68; 85.12 | — |
| SECONDARY Rituximab Cmax and Ctrough in Portion B |
— | — |
| SECONDARY Number of Participants With Positive ADA for PF-05082566 and Rituximab in Portion B |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion B |
1; 0; 1; 0; 1; 1 | — |
| SECONDARY Percentage of Participants Achieving Objective Response Per Cheson 2007 Criteria in Portion B |
33.3; 0; 25.0; 66.7; 0; 0 | — |
| SECONDARY Duration of Response in Portion B |
NA; NA; NA; 12.0; 9.5; NA | — |
| SECONDARY Time to Response in Portion B |
2.1; 2.1; 2.0; 2.1; 3.9; 7.4 | — |
| SECONDARY Progression-Free Survival in Portion B |
NA; 8.1; 11.8; 9.9; 2.1; 5.7 | — |
| SECONDARY Overall Survival in Portion B |
NA; NA; NA; NA; NA; 50.2 | — |
Eligibility Criteria
Inclusion Criteria
- Portion A: Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy or B cell lymphoma, for which no curative therapy is available. Portion A expansion includes patients who have documented disease progression on a checkpoint inhibitor (anti CTLA 4, anti PD1/PD L1 antibodies) per RECIST criteria. Tumor types include metastatic melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NCSLC) and squamous cell carcinoma of the head and neck (SCCHN). Patients in the dose expansion stage are required to provide archival or baseline (obtained during the screening period) tumor biopsies.
- Portion B: Histological confirmed relapsed or refractory CD20 positive NHL for which no curative therapy is available. Patients enrolled in the expansion cohort must have archival tissue available, sampled within 6 months of study entry. The Expansion cohort includes patients with FL or DLBCL with relapsed or refractory disease.
- Measurable disease with at least one extranodal tumor mass >1.0 cm in the greatest transverse diameter (GTD) or in the case of malignant lymph nodes >1.5 cm in the GTD.
- ECOG performance status of ≤ 1.
- Adequate bone marrow function, for Portion A: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥100 x 109/L, hemoglobin >9.0 g/dL. For Portion B: ANC ≥ 1.0 x 109/L, platelet count ≥ 75 x 109/L, and hemoglobin ≥ 8.0 g/dL. In both cases, patients must be transfusion independent at least 14 days prior to screening.
- Serum creatinine ≤ 2 x ULN or estimated creatinine clearance ≥ 50 ml/min.
- Total serum bilirubin ≤ 1.5 x ULN unless the patient has documented Gilbert syndrome and AST and ALT ≤ 2.5 x ULN.
Exclusion Criteria
- Patients with known symptomatic brain metastases requiring steroids.
- Prior allogeneic hematopoietic stem cell transplant.
- Immunosuppressive regimens involving systemic corticosteroids within 14 days before the first dose of study treatment.
- Therapeutic or experimental monoclonal antibodies within 28 day or prior radiation therapy within 14 days of the first dose of study drug.
- Autoimmune disorders and other diseases that compromise or impair the immune system.
- Unstable or serious concurrent medical conditions in the previous 6 months.
- Prior therapy with any anti CD137 monoclonal antibody.
Data sourced from ClinicalTrials.gov (NCT01307267). 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.