Phase 2
Completed N=62
A Safety and Efficacy Trial of JCAR017 Combinations in Subjects With Relapsed/Refractory B-cell Malignancies
Lymphoma, Non-Hodgkin · Lymphoma, Large B-Cell, Diffuse · Lymphoma, Follicular
Source: ClinicalTrials.gov NCT03310619 ↗
Enrolled (actual)
62
Serious AEs
46.8%
Results posted
Apr 2024
Primary outcomePrimary: Number of Participants With Dose-Limiting Toxicity (DLT) — 0; 2; 1; 1 Participants
Summary
This is a global, open-label, multi-arm, parallel multi-cohort, multi-center, Phase 1/2 study to determine the safety, tolerability, PK, efficacy and patient-reported quality of life of JCAR017 in combination with various agents. This protocol is intended to evaluate various drug combinations with JCAR017, as separate arms, over the life of the protocol, using the same objectives. Each combination will be evaluated separately (ie, the intention is not to compare between combinations) for the purposes of the objectives, trial design, and statistical analysis. The following combinations will be tested:
Arm A: JCAR017 in combination with durvalumab Arm B: JCAR017 in combination with CC-122 (avadomide) Arm C: JCAR017 in combination with CC-220 (iberdomide) Arm D: JCAR017 in combination with ibrutinib Arm E: JCAR017 in combination with relatlimab and/or nivolumab Arm F: JCAR017 in combination with CC-99282 Additional arms will be added by way of amendment once combination agents have been selected.
The study will consist of 2 parts: dose finding (Phase 1) and dose expansion (Phase 2). Dose expansion may occur in one or more arms.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose-Limiting Toxicity (DLT) |
0; 2; 1; 1; 0; 0 | — |
| PRIMARY Complete Response Rate (CRR) |
71.4; 62.5; 0.0; 46.7; 0.0; 60.0 | — |
| SECONDARY European Organisation for Research and Treatment of Cancer - Quality of Life C30 Questionnaire (EORTC QLQ-C30) Scores - Phase 2 |
72.92; 80.95; 70.24; 85.71; 75.60; 89.29 | — |
| SECONDARY EuroQol- 5 Dimensions of Health Visual Analogue Scale (EQ-5D VAS) Scores - Phase 2 |
69.5; 82.6; 75.1; 89.1; 77.5; 90.9 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) |
16; 11; 1; 17; 2; 6 | — |
| SECONDARY Number of Participants With Severe Adverse Events (SAEs) |
10; 7; 1; 6; 2; 3 | — |
| SECONDARY Change From Baseline in White Blood Cell and Platelet Numbers |
0.00; 0.03; 0.10; -0.02; 0.05; 0.00 | — |
| SECONDARY Change From Baseline in Percent of White Blood Cells |
0.40; 0.89; 0.00; 0.20; 0.15; 0.88 | — |
| SECONDARY Change From Baseline Erythrocyte Numbers |
-0.11; -0.21; -0.34; -0.10; 0.05; -0.10 | — |
| SECONDARY Change From Baseline Hematocrit Ratio |
0.01; -0.02; -0.04; 0.01; 0.02; -0.01 | — |
| SECONDARY Change From Baseline in Hemoglobin Levels |
0.45; -5.43; -12.00; 1.38; 9.50; -2.50 | — |
| SECONDARY Change From Baseline in Specific Liver Serum Enzyme Levels |
5.45; -2.86; -1.00; -0.58; 0.50; 2.50 | — |
| SECONDARY Change From Baseline in Specific Serum Protein Levels |
4.09; 2.29; 9.00; 1.42; 6.00; 3.50 | — |
| SECONDARY Change From Baseline in Serum Beta-2-Microglobulin Levels |
0.33; 0.06; -0.10; -0.04; -0.65; 0.29 | — |
| SECONDARY Change From Baseline in Serum Bicarbonate Levels |
0.91; 0.00; 0.00; -0.50; 3; -0.50 | — |
| SECONDARY Change From Baseline in Coagulation Times |
-5.70; -0.31; 2.40; -2.25; 4.25; -2.10 | — |
| SECONDARY Change From Baseline in D-Dimer Levels |
-0.92; -0.13; -0.46; -0.69; -0.39; 0.13 | — |
| SECONDARY Change From Baseline in Fibrinogen Levels |
-0.23; -0.65; 2.59; -2.04; -5.12; -1.77 | — |
| SECONDARY Change From Baseline in Prothrombin International Normalized Ratio |
-0.01; 0.08; 0.10; -0.01; -0.20; 0.10 | — |
| SECONDARY Progression-Free Survival (PFS) |
20.90; NA; 2.86; NA; 4.07; 3.06 | — |
| SECONDARY Overall Survival (OS) |
31.34; NA; 2.86; NA; NA; 6.60 | — |
| SECONDARY Overall Response Rate (ORR) |
92.9; 75.0; 100.0; 60.0; 100.00; 60.0 | — |
| SECONDARY Duration of Response (DOR) |
21.45; NA; 1.91; NA; 3.15; 3.29 | — |
| SECONDARY Event-Free Survival (EFS) |
20.90; NA; 2.86; 18.76; 4.07; 3.06 | — |
| SECONDARY Maximum Concentration (Cmax) of JCAR017 by qPCR |
11464.7; 14087.1; 28845.0; 28877.7; 58522.9; 18003.4 | — |
| SECONDARY Time to Maximum Concentration (Tmax) of JCAR017 by qPCR |
10.0; 10.0; 29.0; 14.0; 10.0; 8.5 | — |
| SECONDARY Total Exposure to JCAR017 as Measured by the Area Under the Curve (AUC) by qPCR |
85169.458; 83155.476; 288951.250; 281265.838; 529755.009; 190904.832 | — |
Eligibility Criteria
Inclusion Criteria
- Subject is ≥ 18 years of age at the time of signing the informed consent form ().
- Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
- Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
- Subject must have aggressive B-cell NHL according to "the 2016 revision of the WHO classification of lymphoid neoplasms", histologically confirmed at last relapse by the treating institution, defined as:
- Diffuse large B-cell lymphoma (DLBCL) Not otherwise specified (NOS) including transformed indolent Non-Hodgkin lymphoma (NHL)
- Follicular lymphoma Grade 3B
- T cell/histiocyte-rich large B-cell lymphoma
- Epstein-Barr virus (EBV) positive DLBCL, NOS
- Primary mediastinal (thymic) large B-cell lymphoma
- High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (double/triple-hit lymphoma)
- Subjects disease must have relapsed or be refractory to at least 2 prior lines of therapy. Previous therapy must have included a CD20-targeted agent and an anthracycline.
- Subject must have
- Positron emission tomography (PET)-positive (Deauville score 4 or 5) and computed tomography (CT) measurable disease as per Lugano Classification
- Sum of product of perpendicular diameters (SPD) of up to 6 index lesions ≥ 25 cm2 by CT scan (not applicable to Arm A or B or subjects with Richter's transformation)
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 at screening
- Adequate organ function
- Subjects must agree to not donate blood, organs, sperm or semen, and egg cells for usage in other individuals
- Participants must agree to use effective contraception
Exclusion Criteria
- Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study based on investigator´s judgment.
- Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study based on investigator´s judgment.
- Subject has any condition that confounds the ability to interpret data from the study based on investigator´s judgment.
- Subjects with prior history of malignancies, other than aggressive R/R NHL, unless the subject has been free of the disease for ≥ 2 years with the exception of the following non-invasive malignancies:
- Basal cell carcinoma of the skin
- Squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative.
- Other completely resected stage 1 solid tumor with low risk for recurrence
- Prior treatment with any prior gene therap y product
- Prior treatment with any adoptive T cell therapy; prior hematopoietic stem cell transplant (HSCT) is allowed
- Allogeneic HSCT within 90 days of leukapheresis
- Prior treatment with the combination agent from the assigned arm:
- Anti PD-1 or PD-L1 (Arm A and E)
- CC-122 (Arm B)
- CC-220 (Arm C)
- Prior treatment with ibrutinib is not exclusionary for subjects on any study arm
- Anti LAG-3 targeted agent (Arm E)
- CC-99282 (Arm F)
- Presence of acute or chronic graft-versus-host disease (GVHD)
- Presence of the following:
- Active hepatitis B or active hepatitis C infection
- History of or active human immunodeficiency virus (HIV) infection
- Uncontrolled bacterial, viral or fungal infection at the time of leukapheresis, lymphodepleting chemotherapy or JCAR017 infusion
- Any history of myocarditis (Arm E); history of any one of the following cardiovascular conditions within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stent
Data sourced from ClinicalTrials.gov (NCT03310619). 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.